The physiological and behavioral functions of the body are coordinated into daily patterns that are synchronized with the earth's light/dark cycles. This patterning of function is referred to as circadian rhythms. A central pacemaker located in suprachiasmatic nucleus of the brain serves to coordinate the body's rhythms with the light/dark cycle. Disturbances in normal circadian rhythm have been shown to increase the risk of certain types of cancer, including breast cancer. This effect is so significant that the World Health Organization has recently classified shift work as a probable carcinogen. One effect of alteration in the light/dark cycle such as that experienced by shift workers is a change in the production of the pineal hormone melatonin (N-acetyl-5-methoxytryptamine). Secretion of melatonin is regulated by the suprachiasmatic nucleus. Melatonin has a wide variety of functions including physiological regulation of sleep, modulation of the immune system and antioxidant action. Recent studies have determined that melatonin has oncostatic actions in a variety of cancers, including breast, prostate and endometrial cancer. Thus, this thesis explores the effects of melatonin on clock gene expression and growth of a mouse mammary tumor cell line, EMT6. I hypothesized that growth inhibitory actions of melatonin involve alteration in clock gene expression, induction of apoptosis and cell cycle arrest. Thus, this thesis investigates the modulatory effects of melatonin on clock genes, cell cycle parameters and apoptosis. Western blot analysis and immunocytochemistry confirmed expression of melatonin receptors in the EMT6 cell line. I investigated the circadian rhythm of EMT6 cells by measuring the clock gene expression pattern over a 24 hour period. I found a significant rhythm in Per1 and Per2 transcripts. Expression of estrogen and progesterone receptors was measured as they are putative clock controlled genes involved in the development of breast cancer. The results showed significant rhythm in Per1 (p=0.05), Per2 (p=0.03) and estrogen receptors ERalpha (p=0.001) and ERbeta (p=0.028). Peak expression for Period genes and ERalpha is found at 16 hrs and 20 hrs after serum shock, respectively. Peak expression for ERbeta is found at 24 hours after serum shock. Other steroid hormone receptors such as progesterone receptors PRB and PRA+B were not rhythmic. Treatment with melatonin in a concentration range from 10µM to 1nM inhibited growth in the cells. The antiproliferative effect of melatonin was dose and time dependent. At the end of 48 hours, melatonin at a concentration of 10-7 M induced apoptosis in EMT6 cells as indicated by caspase-3 immunocytochemistry. Furthermore, this same treatment caused an upregulation of the clock gene and putative tumor suppressor gene, Per2. These studies provide evidence that melatonin alters growth of EMT6 cells by inducing caspase-3 and apoptosis, which may be regulated through induction of Per2. Thus, disturbance in rhythmic secretion of melatonin may promote tumor progression in breast cancer.

Cette recherche de thèse est basée sur l'analyse du trait, dans un sens à la fois physique et spirituel. Un trait lancé est comme un mouvement continu; en peignant le trait, dans ma peinture, je me réfère toujours à la pensée du mouvement persistant de l'univers. L'envie pour moi d'exprimer la force mystérieuse de la nature est ainsi omniprésente dans tous mes travaux plastiques. Je considère que les traits que je peins sont la trace du mouvement; qu'ils sont des empreintes qui éprouvent l'énergie vitale intérieure, la fluidité de la pensée, et le rythme du geste de mon corps. De la peinture abstraite au dessin, du trait à l'image de flux, tout l'objectif de ma démarche artistique est le même: entrevoir la vitalité et la fluidité dans la nature, saisir le mouvement imperceptible et la force perpétuelle dans révolution dynamique de l'univers. Grâce à ma tradition orientale (d'origine taïwanaise) enrichie de ma rencontre avec l'Occident, je propose ici une façon personnelle de tracer le trait ou, plus exactement, de peindre le mouvement et l'aspect rythmé de la nature. À travers ce cheminement au plus près du questionnement concernant le trait, la création, la vie. Cette recherche de thèse suivra un processus qui consiste à soulever les apparences pour pénétrer au cœur de qui l'on est et voir apparaître un horizon nouveau. / The research presented in this thesis is based on the analysis of the line, in a physical as well as a spiritual sense. A drawn line is like a continuous movement: when I paint a line my point of reference is always the persistent movement of the universe. The desire to express the mysterious force of nature is therefore omnipresent in all my works. The lines I paint are the trace of the movement: they are the imprints that reflect the inner vital energy. the fluidity of thought and the rhythm of my bodily gesture. Whether it is from abstract painting to drawing or from the line to the image of flow the goal of my artistic approach is the same: ta catch sight of the vitality and fluidity in nature. to capture the imperceptible movement and the perpetual force in the dynamic evolution of the universe. Thanks to my Oriental tradition (Taïwanese origin) enriched by my encounter with the West, I propose a personal way of tracing the line. or, to be more exact. of painting the movement and the rhythmical aspect of nature. Unfolding the questioning concerning the line creation, life. The research in this thesis follows a process that consists in going beyond appearances to penetrate to the core of who one is and see the emergence of a new horizon.

Rhythm is an important dimension of Christian liturgical practice as well as life in the world more generally. Given its significance, this study asks how theology ought to think about the nature and role of rhythm. It puts forward the argument that rhythm is a category of significance for Christian doctrine, particularly the doctrine of salvation, rather than one that pertains only to Christian religious expression (in liturgy for example) or aesthetics. This argument is made on the basis of three factors: (1) the pervasiveness of rhythm in dimensions of human experience that are salient to Christian soteriology, such as relationship and communication, make rhythm a dimension of experience worth theological consideration, (2) the fact that different conceptions of rhythm in various metaphysical accounts have different theological consequences requires theological discussion regarding the nature of rhythm, and (3) the capacity of rhythm to illuminate certain dimensions of the Christian doctrine of salvation such as the nature of participation, the relation between immanent and transcendent, and the relationship between interruption and continuity in Christian soteriology, make it a category that adds to theological understanding. The thesis proposes a definition of rhythm as an oscillation between synchronic form and diachronic experience based in theories of poetic rhythm and supported by theological analysis. The project finds that particular philosophical or theological approaches to metaphysics incorporate either a synchronic or diachronic perspective on rhythm but that both of these perspectives are theologically problematic on their own, the former tending to an illusory perspective on the whole from a God's-eye-view and the latter tending towards a strict division between creature and creator such that the relationship between them is one of rupture and confrontation only and not salvific. The thesis therefore proposes an oscillation on the part of the theologian between these two perspectives after the metaphysics of Erich Przywara and demonstrates this approach to be appropriate to the Christian doctrine of salvation.

Subterranean rodents are interesting model group for studying of the circadian timing system due to their cryptic lifestyle and challenging living conditions. The filed data indicate that the locomotor activity of the silvery mole-rat (Heliophobius argenteocinereus) is influenced by temperature cycle, but the confirmation in laboratory study was to date missing.

The current dissertation is a systematic study of variation in the English spoken in multilingual and multicultural India. Three experiments were conducted to investigate the influence of two native languages (Hindi and Telugu) on English, which is spoken by almost all Indians as a second language. The first experiment indicated that Indian English (IE) is accented by the first language of its speakers, but high English proficiency and the degree of divergence between the sound patterns of the speaker's native language and his or her IE suggested that other factors might influence the preservation of a native language accent in IE. The second experiment controlled for language investigated the effect of region on IE, finding that listeners were able to distinguish speakers based on region even when they spoke the same native language. The regional variation in IE was more noticeable for native Telugu speakers than for native Hindi speakers. This difference was attributed to differences in the social and political power associated with these native languages: Hindi being the national language and the language of the capital city of India; Telugu, a regional language of Andhra Pradesh and spoken by many fewer people than Hindi. The third experiment was motivated by the idea that persistent effects of the speaker's native language might also be used to reflect a speaker's personal identity. Accordingly, the experiment investigated the effect of speaking about personal versus neutral topics on IE pronunciation. The results were that speakers' IE pronunciation was more like their native language when speakers discussed personal topics then when they discussed neutral topics. Overall, the results suggest that the pronunciation of IE is conditioned by social factors, meaning that it has entered the differentiation phase of Schneider's dynamic model of English evolution. This dissertation includes previously published co-authored material.

O câncer de mama é o tipo de câncer que mais acomete as mulheres e a principal causa de morte na faixa entre 40 e 55 anos. Apesar de apresentar variação internacional, suas taxas seguem aumentando mundialmente, sendo até cinco vezes mais frequente em países desenvolvidos. A industrialização gera aumento da exposição à luz durante a noite, o que causa supressão de melatonina. A melatonina é o principal hormônio secretado pela glândula pineal e possui atividade oncostática e antioxidante, interfere no controle do ciclo celular, função imunológica e nos hormônios esteróides. O objetivo desta dissertação e apresentar o racional e o desenvolvimento do estudo cujo objetivo foi avaliar o efeito da terapia com melatonina sobre o desenvolvimento de tumores mamários em ratas expostas ou não a dessincronização circadiana. A indução da carcinogênese mamária foi através de administração intragástrica de DMBA em 39 ratas Sprague-dawley entre 41 e 46 dias. Os animais foram randomizados em 04 grupos, Sincronizados sem tratamento, Dessincronizados sem tratamento, Sincronizados com melatonina e Dessincronizados com melatonina. Os grupos Sincronizados foram mantidos em ciclo claro/escuro de 12/12 horas e os dessincronizados a ciclo claro/escuro de 11/11 horas, durante 8 semanas. O desenvolvimento tumoral ocorreu em 32 animais (82,05%), totalizando 73 tumores. A melatonina apresentou efeitos benéficos quanto a multiplicidade tumoral, grau histológico, tamanho dos tumores e peso dos animais, enquanto que a dessincronização não interferiu de forma significativa na carcinogênese mamária. / Breast cancer is the type of cancer that most affects women and the leading cause of death in the age between 40 and 55 years. Despite presenting international variation, their rates continue to increase worldwide, with up to five times more common in developed countries. The industrialization generates increased exposure to light at night, which causes suppression of melatonin. Melatonin is the main hormone secreted by the pineal gland and has oncostatic and antioxidant activity, interferes with cell cycle control, immune function and steroid hormones. The aim of this dissertation and present the rationale and development of the study whose objective was to evaluate the effect of melatonin therapy on the development of mammary tumors in rats exposed or not the circadian desynchronization. Induction of mammary carcinogenesis was via intragastric administration of DMBA in 39 Sprague- Dawley rats between 41 and 46 days. The animals were randomized into 04 groups, Synchronized and untreated, desynchronized and untreated, synchronized and with melatonin, desynchronized and with melatonin. Synchronized Groups were kept in a light / dark cycle of 12/12 hours and the desynchronized in a light / dark cycle of 11/11 hours for 8 weeks. The tumor development occurred in 32 animals (82.05%), totaling 73 tumors. Melatonin showed beneficial effects on tumor multiplicity, histological grade, tumor size and weight of the animals, while desynchronization did not interfere significantly in breast carcinogenesis.

There is a need for improved understanding of interactions between electromagnetic fields and biological tissues. In this thesis, the effects of exposure to 50 Hz magnetic fields, associated with power generation and use, and 1800 MHz fields associated with mobile phones were investigated with particular focus on the plastic processes that are involved in cognitive function. After repeated, daily exposure of young adult C57Bl/6J mice to an 1800 MHz field at 3 W/kg, very subtle changes in expression of genes involved in synaptic plasticity were found (p < 0.05). Spatial memory as measured in the water maze was not significantly affected by exposure. Exposure at 0.3 W/kg did not significantly affect any of the endpoints (p > 0.05). Indications of a greater sensitivity to exposure at 3 W/kg were seen in a senescence accelerated prone mouse model (SAMP8) compared to a resistant strain (SAMR1). However, only subtle effects of exposure were seen. Exposure of young C57Bl/6J mice to a 50 Hz field at 100 or 300 μT induced small but significant changes in expression in synaptic plasticity related genes (p < 0.05). Furthermore, repeated exposure significantly increased microglial density in the dorsal hippocampus (p < 0.05) and slightly decreased proliferation in the dorsal hippocampus (100 μT, p < 0.05). Spatial memory was not significantly affected by exposure. Acute exposure to a 50 Hz magnetic field for 30 minutes at 300 or 580 μT did not affect the adrenal response to a nocturnal white or blue light shock, while exposure at 580 μT in the absence of light significantly decreased per1 expression in the adrenal glands (p < 0.05), but not in the liver or dorsal hippocampus. Exposure at 580 μT for 24 hours had only minor transient effects on the rhythmic expression of the core clock genes. In summary, exposure to 50 Hz or 1800 MHz fields caused subtle and transient changes to some molecular mechanisms and cells involved in cognitive function and circadian rhythm control.

Made available in DSpace on 2015-08-20T17:10:12Z (GMT). No. of bitstreams: 0 Previous issue date: 2015-04-27. Added 1 bitstream(s) on 2015-08-20T17:25:47Z : No. of bitstreams: 1 000840969.pdf: 10049788 bytes, checksum: 6c4e91dba8d36986ad74ef7ff86b1a29 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Tanto sucesso de bilheteria quanto possível desafeto da crítica canônica, de fato, o cinema hollywoodiano é um tema pouco presente em teses brasileiras. Nos entornos dessa relação, ora contratual, ora polêmica (entre público, crítica e arte), serão descritas as estratégias semióticas no âmbito dos processos de significação inerentes ao cinema, de maneira a explicar, a partir dos processos semióticos visuais, a organização dos ritmos de expressão e de conteúdo possíveis que os filmes de Hollywood contemporâneos são capazes de manifestar. Ao explicar a organização dos planos de conteúdo e de expressão dos filmes mais vistos na primeira década deste século, defendem-se hipóteses em torno dos diferentes tipos de estrutura fílmica, conforme a incidência de ritmos paratáticos e hipotáticos (com efeito predominantemente sintagmático ou paradigmático), de aspecto contínuo ou descontínuo. Essas noções terão como ponto de partida os conceitos estruturalistas (Saussure, Roman Jakobson, Christian Metz) e como ponto de chegada a semiótica discursiva (Algirdas J. Greimas e Joseph Courtés), a plástica (Jean-Marie Floch), e a do ritmo (Louis Hébert). O corpus é organizado a partir dos filmes mais vistos na última década, de 2001 a 2010 (segundo o site Box Office Mojo). Será examinado um conjunto de unidades significantes (as sequências relevantes) de quatro filmes mais vistos: Avatar (2009), de James Cameron, Piratas do Caribe - o baú da morte (2006), de Gore Verbinski, Toy story 3, de Lee Unkrich (2010), e O Senhor dos anéis - o retorno do rei, de Peter Jackson (2003). Tendo como meta a descrição dos processos de significação na linguagem cinematográfica, serão estabelecidos critérios semióticos que ajudem a observar as relações estruturais pertinentes nos filmes em questão (quando possível, comparando-os a outras semióticas visuais e verbovisuais), a fim de indicar diferenças e... / Both box office success and possible disaffection of canonical criticism, in fact, the Hollywoodian cinema is a theme not too attractive in Brazilian academic theses. In the surroundings of this relationship - sometimes contractual, sometimes controversy (since they involve different opinions amongst public, critics and art) - it is necessary to describe the semiotics strategies within the meaning processes inherent to the movies, in order to explain, by means semiotics visual processes theory, the organization of expression rhythms and content rhythms that contemporary Hollywood films are able to manifest. In explaining the organization of plane of content and plane of expression of the most viewed films on the first decade of this century it is possible to defend hypotheses on different types of film structure, as the incidence of paratactic and hypotactic rhythms (with predominantly syntagmatic or paradigmatic effects), which aspect can be continuous or discontinuous. These concepts have a starting point on the structuralism (Saussure, Roman Jakobson, Christian Metz) and an arrival point on discursive semiotics (Algirdas J. Greimas and Courtes Joseph), also on the plastic approach (Jean-Marie Floch ) and on the studies of rhythm (Louis Hébert). The corpus is organized from the most viewed films in the last decade, from 2001 to 2010 (according to Box Office Mojo website). A set of significant units (the relevant sequences) four most watched movies will be analized: James Cameron's Avatar (2009), Gore Verbinski's Pirates of the Caribbean (2006), Lee Unkrich's Toy Story 3 (2010) and Peter Jackson's Lord of the Rings (2003). In order to describe the processes of meaning in film language, semiotic principles will be established to help observe and analize the relevant structural and resemblances in the movies mentioned (when possible, comparing them to other visual and verbal visual objects), to indicate differences and ...

O câncer de mama é o tipo de câncer que mais acomete as mulheres e a principal causa de morte na faixa entre 40 e 55 anos. Apesar de apresentar variação internacional, suas taxas seguem aumentando mundialmente, sendo até cinco vezes mais frequente em países desenvolvidos. A industrialização gera aumento da exposição à luz durante a noite, o que causa supressão de melatonina. A melatonina é o principal hormônio secretado pela glândula pineal e possui atividade oncostática e antioxidante, interfere no controle do ciclo celular, função imunológica e nos hormônios esteróides. O objetivo desta dissertação e apresentar o racional e o desenvolvimento do estudo cujo objetivo foi avaliar o efeito da terapia com melatonina sobre o desenvolvimento de tumores mamários em ratas expostas ou não a dessincronização circadiana. A indução da carcinogênese mamária foi através de administração intragástrica de DMBA em 39 ratas Sprague-dawley entre 41 e 46 dias. Os animais foram randomizados em 04 grupos, Sincronizados sem tratamento, Dessincronizados sem tratamento, Sincronizados com melatonina e Dessincronizados com melatonina. Os grupos Sincronizados foram mantidos em ciclo claro/escuro de 12/12 horas e os dessincronizados a ciclo claro/escuro de 11/11 horas, durante 8 semanas. O desenvolvimento tumoral ocorreu em 32 animais (82,05%), totalizando 73 tumores. A melatonina apresentou efeitos benéficos quanto a multiplicidade tumoral, grau histológico, tamanho dos tumores e peso dos animais, enquanto que a dessincronização não interferiu de forma significativa na carcinogênese mamária. / Breast cancer is the type of cancer that most affects women and the leading cause of death in the age between 40 and 55 years. Despite presenting international variation, their rates continue to increase worldwide, with up to five times more common in developed countries. The industrialization generates increased exposure to light at night, which causes suppression of melatonin. Melatonin is the main hormone secreted by the pineal gland and has oncostatic and antioxidant activity, interferes with cell cycle control, immune function and steroid hormones. The aim of this dissertation and present the rationale and development of the study whose objective was to evaluate the effect of melatonin therapy on the development of mammary tumors in rats exposed or not the circadian desynchronization. Induction of mammary carcinogenesis was via intragastric administration of DMBA in 39 Sprague- Dawley rats between 41 and 46 days. The animals were randomized into 04 groups, Synchronized and untreated, desynchronized and untreated, synchronized and with melatonin, desynchronized and with melatonin. Synchronized Groups were kept in a light / dark cycle of 12/12 hours and the desynchronized in a light / dark cycle of 11/11 hours for 8 weeks. The tumor development occurred in 32 animals (82.05%), totaling 73 tumors. Melatonin showed beneficial effects on tumor multiplicity, histological grade, tumor size and weight of the animals, while desynchronization did not interfere significantly in breast carcinogenesis.

Orientador: Eliana Ayoub / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Educação / Made available in DSpace on 2018-08-07T01:03:53Z (GMT). No. of bitstreams: 1 Presta_MichelleGuidiGargantini_M.pdf: 952428 bytes, checksum: bda8c1c50f5294474224adad3415353e (MD5) Previous issue date: 2006 / Mestrado / Educação, Conhecimento, Linguagem e Arte / Mestre em Educação