In the present monograph we study in detail the primordial gravitational waves in cosmologies with a decaying vacuum. The decaying vacuum models are an alternative to solve the cosmological constant problem attributing a dynamic to the vacuum energy. The problem of primordial gravitational waves is discussed in the framework of an expanding, flat, spatially homogeneous and isotropic FLRW Universe described by General Relativity theory with decaying vacuum energy density of the type $\\Lambda \\equiv \\Lambda(H)$. Two particular interesting limits of a class of decaying vacuum models were investigated. A first-order tensor perturbation term was introduced to the FLRW metric, the evolution equation of the perturbations was derived and then expressed in terms of a Fourier expansion, the time-dependent part decouples from the spatial part. The resulting equation has the form of a damped harmonic oscillator which depends on the scale factor, which carries all the cosmological and decaying vacuum characteristics. In the first model studied, the decaying vacuum has the form $\\Lambda \\propto H^2$. The gravitational wave equation is established and its time-dependent part has analytically been solved for different epochs in the case of a flat geometry. The main result is unlike the standard $\\Lambda$CDM cosmology (no interacting vacuum): in this model there is gravitational wave amplification during the radiation era, which in quantum field theory means graviton production. This difference is a clear signature of the decaying vacuum models which a eventual observation could give empirical clues about it. However, high frequency modes are damped out even faster than in the standard cosmology, both in the radiation and matter-vacuum dominated epoch. The physical gravitational wave quantities like the modulus of the mode function, power and gravitational wave energy density spectra generated at different cosmological eras are also explicitly evaluated. The second model studied is a decaying vacuum of the form $\\Lambda \\propto H^3$. This model drives a nonsingular flat cosmology which is termed complete in the sense that the cosmic evolution occurs between two extreme de Sitter stages. The particularity which makes interesting this model is that the transition from the early de Sitter era to the radiation phase is smooth avoiding the graceful exit problem. The gravitational wave equation is derived and its time-dependent part numerically integrated in a relevant period previously delimited. The gravitational wave solutions for the other eras were calculates analytically. Today\'s gravitational wave spectra were calculated and compared with the standard result where an abrupt transition is assumed. It is found that the stochastic background of gravitational waves is very similar to the one predicted by the cosmic concordance model plus inflation except for the higher frequencies. / Na presente monografia foi estudado em detalhe as ondas gravitacionais primordiais em cosmologias com decaimento do vácuo. Os modelos de decaimento do vácuo são uma alternativa para resolver o problema da constante cosmológica atribuindo uma dinâmica à energia do vácuo. O problema de ondas gravitacionais primordiais é discutida no âmbito de um Universo FLRW em expansão, plano, espacialmente homogêneo e isotrópico descrito pela teoria da Relatividade Geral com decaimento da densidade de energia do vácuo do tipo $\\Lambda \\equiv \\Lambda(H)$. Dois limites particularmente interessantes de uma classe de modelos de decaimento do vácuo foram trabalhados. Um termo tensorial perturbativo a primeira ordem foi introduzido na métrica de FLRW, a equação de evolução das perturbações foi derivada e depois expressada em termos de uma expansão de Fourier, a parte dependente do tempo desacopla-se da parte espacial. A equação resultante tem a forma de um oscilador harmônico amortecido que depende do fator de escala que carrega todas as características cosmológicos e do decaimento do vácuo. No primeiro modelo estudado, o decaimento do vácuo tem a forma $\\Lambda \\propto H^2$. A equação da onda gravitacional é estabelecida e a sua parte dependente do tempo foi resolvida analiticamente para diferentes épocas no caso de uma geometria plana. O resultado principal é que a diferença da cosmologia $\\Lambda$CDM padrão (sem decaimento do vácuo), neste modelo ocorre amplificação de ondas gravitacionais durante a era de radiação, que em mecânica quântica significa produção gráviton. Esta diferença é uma assinatura clara dos modelos de decaimento do vácuo que uma eventual observação poderia dar pistas empíricas sobre o assunto. No entanto, os modos de alta frequência são amortecidos ainda mais rápido do que na cosmologia padrão, tanto na era da radiação e da matéria-vácuo. As quantidades físicas das ondas gravitacionais, como o módulo da função de modos, espectros de potência e de densidade de energia de onda gravitacional geradas em diferentes eras cosmológicas também foram avaliadas explicitamente. O segundo modelo estudado é um decaimento do vácuo da forma $\\Lambda \\propto H^3$. Este modelo leva uma cosmologia plana não singular que é denominado completo no sentido de que a evolução cósmica ocorre entre duas eras de Sitter extremas. A particularidade que torna interessante este modelo é que a transição do início da era de Sitter era para a fase da radiação é suave evitando o graceful exit problem. A equação gravitacional é derivada e sua parte dependente do tempo foi integrada numericamente num período relevante previamente delimitado, as soluções das ondas gravitacionais para as outras eras foram calculadas analiticamente. Os espectros de hoje das ondas gravitacionais foram calculados e comparados com os cálculos padrão onde é assumida uma transição abrupta. Verificou-se que o fundo estocástico de ondas gravitacionais é muito semelhante ao previsto pelo modelo de concordância cósmica mais a inflação, exceto para as frequências mais altas.

In the present monograph we study in detail the primordial gravitational waves in cosmologies with a decaying vacuum. The decaying vacuum models are an alternative to solve the cosmological constant problem attributing a dynamic to the vacuum energy. The problem of primordial gravitational waves is discussed in the framework of an expanding, flat, spatially homogeneous and isotropic FLRW Universe described by General Relativity theory with decaying vacuum energy density of the type $\\Lambda \\equiv \\Lambda(H)$. Two particular interesting limits of a class of decaying vacuum models were investigated. A first-order tensor perturbation term was introduced to the FLRW metric, the evolution equation of the perturbations was derived and then expressed in terms of a Fourier expansion, the time-dependent part decouples from the spatial part. The resulting equation has the form of a damped harmonic oscillator which depends on the scale factor, which carries all the cosmological and decaying vacuum characteristics. In the first model studied, the decaying vacuum has the form $\\Lambda \\propto H^2$. The gravitational wave equation is established and its time-dependent part has analytically been solved for different epochs in the case of a flat geometry. The main result is unlike the standard $\\Lambda$CDM cosmology (no interacting vacuum): in this model there is gravitational wave amplification during the radiation era, which in quantum field theory means graviton production. This difference is a clear signature of the decaying vacuum models which a eventual observation could give empirical clues about it. However, high frequency modes are damped out even faster than in the standard cosmology, both in the radiation and matter-vacuum dominated epoch. The physical gravitational wave quantities like the modulus of the mode function, power and gravitational wave energy density spectra generated at different cosmological eras are also explicitly evaluated. The second model studied is a decaying vacuum of the form $\\Lambda \\propto H^3$. This model drives a nonsingular flat cosmology which is termed complete in the sense that the cosmic evolution occurs between two extreme de Sitter stages. The particularity which makes interesting this model is that the transition from the early de Sitter era to the radiation phase is smooth avoiding the graceful exit problem. The gravitational wave equation is derived and its time-dependent part numerically integrated in a relevant period previously delimited. The gravitational wave solutions for the other eras were calculates analytically. Today\'s gravitational wave spectra were calculated and compared with the standard result where an abrupt transition is assumed. It is found that the stochastic background of gravitational waves is very similar to the one predicted by the cosmic concordance model plus inflation except for the higher frequencies. / Na presente monografia foi estudado em detalhe as ondas gravitacionais primordiais em cosmologias com decaimento do vácuo. Os modelos de decaimento do vácuo são uma alternativa para resolver o problema da constante cosmológica atribuindo uma dinâmica à energia do vácuo. O problema de ondas gravitacionais primordiais é discutida no âmbito de um Universo FLRW em expansão, plano, espacialmente homogêneo e isotrópico descrito pela teoria da Relatividade Geral com decaimento da densidade de energia do vácuo do tipo $\\Lambda \\equiv \\Lambda(H)$. Dois limites particularmente interessantes de uma classe de modelos de decaimento do vácuo foram trabalhados. Um termo tensorial perturbativo a primeira ordem foi introduzido na métrica de FLRW, a equação de evolução das perturbações foi derivada e depois expressada em termos de uma expansão de Fourier, a parte dependente do tempo desacopla-se da parte espacial. A equação resultante tem a forma de um oscilador harmônico amortecido que depende do fator de escala que carrega todas as características cosmológicos e do decaimento do vácuo. No primeiro modelo estudado, o decaimento do vácuo tem a forma $\\Lambda \\propto H^2$. A equação da onda gravitacional é estabelecida e a sua parte dependente do tempo foi resolvida analiticamente para diferentes épocas no caso de uma geometria plana. O resultado principal é que a diferença da cosmologia $\\Lambda$CDM padrão (sem decaimento do vácuo), neste modelo ocorre amplificação de ondas gravitacionais durante a era de radiação, que em mecânica quântica significa produção gráviton. Esta diferença é uma assinatura clara dos modelos de decaimento do vácuo que uma eventual observação poderia dar pistas empíricas sobre o assunto. No entanto, os modos de alta frequência são amortecidos ainda mais rápido do que na cosmologia padrão, tanto na era da radiação e da matéria-vácuo. As quantidades físicas das ondas gravitacionais, como o módulo da função de modos, espectros de potência e de densidade de energia de onda gravitacional geradas em diferentes eras cosmológicas também foram avaliadas explicitamente. O segundo modelo estudado é um decaimento do vácuo da forma $\\Lambda \\propto H^3$. Este modelo leva uma cosmologia plana não singular que é denominado completo no sentido de que a evolução cósmica ocorre entre duas eras de Sitter extremas. A particularidade que torna interessante este modelo é que a transição do início da era de Sitter era para a fase da radiação é suave evitando o graceful exit problem. A equação gravitacional é derivada e sua parte dependente do tempo foi integrada numericamente num período relevante previamente delimitado, as soluções das ondas gravitacionais para as outras eras foram calculadas analiticamente. Os espectros de hoje das ondas gravitacionais foram calculados e comparados com os cálculos padrão onde é assumida uma transição abrupta. Verificou-se que o fundo estocástico de ondas gravitacionais é muito semelhante ao previsto pelo modelo de concordância cósmica mais a inflação, exceto para as frequências mais altas.

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Mammalian females form their germ cells (oocytes) before or shortly after birth. The oocytes interact with somatic cells to form primordial follicles, creating the quiescent population from which oocytes will be recruited to grow throughout life. A female’s fertility life span is therefore, dependant on the size of this pool and the rate at which primordial follicle are activated to grow. However, there is still much we do not know about the quiescent follicle population and the mechanisms that control their recruitment into the growing follicle population are still unclear. There is evidence that the phosphoinositide-3-kinase (PI3K) pathway is key to activation of follicle growth. The role of the PI3K pathway has been primarily explored in the rodent model and has highlighted this pathway’s importance both in the activation of quiescent follicle growth and maintaining dormancy of the quiescent follicle population. This thesis aimed to explore if the PI3K pathway played a similar role in a large mono-ovulatory species as it does in the small polyovulatory rodent species. Bovine is a mono-ovulate species, which has similar attributes in its reproduction and folliculogenesis to the human in vivo; therefore using an in vitro bovine model might be a valuable indication of the role of the PI3K pathway in the human. Initial experiments tested if the bovine was a good model for human primordial follicle activation in an in vitro environment. It was observed that the bovine and human had comparative levels of activation and subsequent increases in both the primary and secondary follicle populations within an in vitro culture system. These similarities indicate that the bovine is a relevant model for the human in vitro. It is not possible to culture the entire bovine ovary. Therefore knowing the location of the primordial follicles is important to establishing what region(s) of the ovary to use. The overall concentration of ovarian follicles was higher in the cortex and gradually declined through the consecutive inner layers of the ovary. The distribution of the ovarian follicle populations were different in each distinctive region of the ovary with the quiescent follicles representing a much larger proportion of the ovarian follicle population in the cortex compared to the inner regions of the ovary. The location an ovarian follicle in the ovary was seen to influence its health in both the quiescent and growing follicle populations, with reduced health seen in the IV inner layers of the ovary compared to the cortex. This resulted in very few healthy quiescent follicles outside of the cortex region making it the more favourable region to culture in functional studies. The role of the PI3K pathway was therefore explored using an in vitro bovine model using the pharmacological compounds bpV (HOpic) and 740Y-P, both of which caused an up-regulation of the PI3K-pathway. It was observed that up-regulation of the PI3K pathway caused an increase in the activation of the quiescent follicle population, and the resulting primary follicles were larger in size. However, there was reduced health in both the growing and quiescent follicle populations. The ill health appears to be due to a disruption in the co-ordination of growth between oocyte and granulosa cells in the ovarian follicles, leading to enlarged oocytes in both the primary follicles and quiescent follicles. Although the PI3K pathway caused an increase in quiescent follicle activation and larger primary follicles there was no increase in the number of viable large secondary follicles obtained. The growth of the secondary follicles was unaltered by the initial activation of the quiescent follicles via the PI3K pathway. These experiments show that the PI3K pathway plays a role in primordial follicle activation in large mono-ovulate species. However, up-regulating the PI3K pathway results in a decrease in health of the quiescent and primary follicle populations, thus limiting its immediate value as a therapeutic target. This study has improved our understanding of the role of the PI3K pathway in primordial follicle activation in a large mono-ovulate species. It has highlighted that the up-regulation of the PI3K pathway using both bpV (HOpic) and 740Y-P increases the activation of the bovine ovarian follicles in vitro. However, up-regulating the PI3K pathway disrupts the development of the ovarian follicles resulting in retarded growth and thereby a decrease in the survival of both the quiescent and growing follicle populations. The similarities in activation, growth and development between the bovine and the human in vitro indicate that the results observed in the bovine are a good indication of what would occur in the human. This study has also improved our understanding of the location, distribution and viability of the ovarian follicle population within the ovary.

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>Magister Scientiae - MSc / Next-generation surveys of the large-scale structure of the Universe will be of great importance in allowing us to extract invaluable information about the nature of the Universe and the physical laws that govern it, at a higher precision than previously possible. In particular, they will allow us to more closely study primordial non-Gaussianity, a feature which leaves an imprint on the power spectrum of galaxies on the ultra-large scales and which acts as a powerful probe of the physics of the early Universe. To investigate the extent to which upcoming surveys will be able to improve our knowledge of primordial non-Gaussianity, we perform a forecast to predict the observational constraints on local-type primordial non-Gaussianity, as well as an extension that includes a scale dependence. We study the constraining power of a multi-tracer approach, where information from different surveys is combined to help suppress cosmic variance and break parameter degeneracies. More specifically, we consider the combination of a 21cm intensity mapping survey with each of two different photometric galaxy surveys, and also examine the effect of including CMB lensing as an additional probe. The forecast constraint from a combination of SKA1, a Euclid-like (LSST-like) survey and a CMB Stage 4 lensing experiment is (fNL) ' 0:9 (1:4) which displays a factor of 2 improvement over the case without CMB lensing, indicating that the surveys considered are indeed complementary. The constraints on the running index of the scale-dependent model are forecast as (nNL) ' 0:12 (0:22) from the same combination of surveys.

The primordial follicle pool is the main source of developing follicles in the ovary. The length of reproductive life and the onset of menopause are governed by the amount of primordial follicles in the ovary. The genetic factors and molecular mechanisms that maintain the primordial follicles in a dormant and surviving state for the whole of reproductive life are not well understood. The phosphatidylinositol 3 kinase (PI3K) signaling pathways in the oocyte that control oocyte growth and early follicular development are largely unknown. The major aim of this thesis was to investigate the functional role of the intra-oocyte PI3K pathway in the regulation of primordial follicle activation and survival.  Phosphatase and tensin homolog deleted on chromosome ten (PTEN) is a major negative regulator of PI3K. The conditional deletion of Pten in the oocytes of primordial follicles led to the overgrowth of oocytes and activation of the entire pool of primordial follicles. There were higher numbers of activated primordial follicles at postnatal day 8 (PD8) in ovaries lacking PTEN in oocytes; by PD35 all the primordial follicles were activated and all the follicles were depleted by 12 weeks, causing premature ovarian failure (POF). In addition, the rate of follicular death that occurs during sexual maturity is reduced in ovaries that lack PTEN in oocytes. Further mechanistic studies revealed that loss of Pten in oocytes resulted in elevated Akt signaling and upregulation of both expression and activation of ribosomal protein S6 (rpS6). The overactivation of primordial follicles in ovaries that lack PTEN in oocytes is believed to be due to elevated expression and activation of rpS6. PTEN in oocytes is indispensable for the maintenance of primordial follicles in dormancy.  To study the role of the intra-oocyte PI3K signaling pathway in controlling the survival and maintenance of primordial follicles, 3-phosphoinositide-dependent protein kinase-1 (PDK1) was deleted in oocytes of primordial follicle. The loss of Pdk1 in oocytes led to the depletion of most primordial follicles around the onset of sexual maturity, causing POF during early adulthood. Furthermore, the activation of Akt, p70 S6 kinase 1 (S6K1), and rpS6 was impaired in oocytes that lacked PDK1. The suppressed PDK1–Akt–S6K1–rpS6 signaling in oocytes appears to be responsible for the loss of primordial follicles. The excessive activation of primordial follicles seen in the absence of Pten in oocytes could be reversed by concurrent deletion of Pdk1. In addition, the elevated activation of Akt and S6K1 in the absence of PTEN in oocytes was not observed in PTEN and PDK1 double mutant mice. Similarly, the hyperphosphorylation of rpS6 in oocytes that lack PTEN was prevented in double mutant mice, which was most likely due to downregulation of S6K1 activation. Thus, inactivation of rpS6 in double mutant mice might be the reason for the prevention of excessive primordial follicular activation and survival.  PTEN and PDK1 in oocytes are essential for the maintenance of quiescence and survival of primordial follicles. The molecular network involving PI3K/PTEN–PDK1 signaling in oocyte controls the survival, loss, and activation of primordial follicles, which together govern reproductive aging and determine the length of reproductive life in females. The results of the above studies indicate that the mammalian oocyte serves as the seat of programming of follicular activation and survival.

京都大学 / 0048 / 新制・課程博士 / 博士(理学) / 甲第20900号 / 理博第4352号 / 新制||理||1625(附属図書館) / 京都大学大学院理学研究科物理学・宇宙物理学専攻 / (主査)教授 田中 貴浩, 教授 向山 信治, 教授 川合 光 / 学位規則第4条第1項該当 / Doctor of Science / Kyoto University / DFAM

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