No description available.

Hedgehog (Hh) proteins control animal development and tissue homeostasis. They activate gene expression by regulating processing, stability, and activation of Gli/Cubitus interruptus (Ci) transcription factors. Hh proteins are secreted and spread through tissue, despite becoming covalently linked to sterol during processing. Multiple mechanisms have been proposed to release Hh proteins in distinct forms; in Drosophila, lipoproteins facilitate long-range Hh mobilization but also contain lipids that repress the pathway. Here, we show that mammalian lipoproteins have conserved roles in Sonic Hedgehog (Shh) release and pathway repression. We demonstrate that lipoprotein-associated forms of Hh and Shh specifically block lipoprotein-mediated pathway inhibition. We also identify a second conserved release form that is not sterol-modified and can be released independently of lipoproteins (Hh-N*/Shh-N*). Lipoprotein-associated Hh/Shh and Hh-N*/Shh-N* have complementary and synergistic functions. In Drosophila wing imaginal discs, lipoprotein-associated Hh increases the amount of full-length Ci, but is insufficient for target gene activation. However, small amounts of non-sterol-modified Hh synergize with lipoprotein-associated Hh to fully activate the pathway and allow target gene expression. The existence of Hh secretion forms with distinct signaling activities suggests a novel mechanism for generating a diversity of Hh responses.

Distance sampling is one of the most commonly used methods for estimating density and abundance. Conventional methods are based on the distances of detected animals from the center of point transects or the center line of line transects. These distances are used to model a detection function: the probability of detecting an animal, given its distance from the line or point. The probability of detecting an animal in the covered area is given by the mean value of the detection function with respect to the available distances to be detected. Given this probability, a Horvitz-Thompson- like estimator of abundance for the covered area follows, hence using a model-based framework. Inferences for the wider survey region are justified using the survey design. Conventional distance sampling methods are based on a set of assumptions. In this thesis I present results that extend distance sampling on two fronts. Firstly, estimators are derived for situations in which there is measurement error in the distances. These estimators use information about the measurement error in two ways: (1) a biased estimator based on the contaminated distances is multiplied by an appropriate correction factor, which is a function of the errors (PDF approach), and (2) cast into a likelihood framework that allows parameter estimation in the presence of measurement error (likelihood approach). Secondly, methods are developed that relax the conventional assumption that the distribution of animals is independent of distance from the lines or points (usually guaranteed by appropriate survey design). In particular, the new methods deal with the case where animal density gradients are caused by the use of non-random sampler allocation, for example transects placed along linear features such as roads or streams. This is dealt with separately for line and point transects, and at a later stage an approach for combining the two is presented. A considerable number of simulations and example analysis illustrate the performance of the proposed methods.

Este trabalho teve por finalidade simular a hidrodinâmica da Plataforma Continental Interna do Estado de São Paulo (PCISP) e da Plataforma Continental Média do Estado de São Paulo (PCMSP) no período de verão, em resposta às forçantes do gradiente de densidade, do vento climatológico e das marés, através da implementação do modelo numérico hidrodinâmico tridimensional Regional Ocean Modeling System (ROMS). Os experimentos realizados mostraram que os efeitos da distribuição de densidade sobre o comportamento geral da circulação na PCISP e PCMSP são secundários quando comparados à circulação induzida pela tensão de cisalhamento do vento. Os resultados apontam que na PCISP e na PCMSP a componente de velocidade paralela à costa é dominada por forçantes de frequência subinercial, como o vento climatológico e o gradiente de densidade, enquanto que a componente normal, na direção normal à costa, é fortemente influenciada pela forçante de maré. / The aim of this study was simulate the hydrodynamic of the Inner Continental Shelf of the State of São Paulo (PCISP) and of the Mid Continental Shelf of the State of São Paulo (PCMSP) during summer, in response to the density gradient forcing, to the climatological wind shear stress forcing and to the tide forcing, applying the tridimensional hydrodynamic numeric model Regional Ocean Modeling System (ROMS). The experiments performed showed the effects of the density distribution over the general circulation behavior in the PCISP and PCMSP are secondary compared with the induced climatological wind shear stress circulation. The results indicate that in the PCISP and in the PCMSP the component velocity parallel to the coast is dominated by subinertial frequencies forcing, as the climatological wind and the density gradient, while the component velocity perpendicular to the coast is strongly influenced by the tide forcing.

Este trabalho teve por finalidade simular a hidrodinâmica da Plataforma Continental Interna do Estado de São Paulo (PCISP) e da Plataforma Continental Média do Estado de São Paulo (PCMSP) no período de verão, em resposta às forçantes do gradiente de densidade, do vento climatológico e das marés, através da implementação do modelo numérico hidrodinâmico tridimensional Regional Ocean Modeling System (ROMS). Os experimentos realizados mostraram que os efeitos da distribuição de densidade sobre o comportamento geral da circulação na PCISP e PCMSP são secundários quando comparados à circulação induzida pela tensão de cisalhamento do vento. Os resultados apontam que na PCISP e na PCMSP a componente de velocidade paralela à costa é dominada por forçantes de frequência subinercial, como o vento climatológico e o gradiente de densidade, enquanto que a componente normal, na direção normal à costa, é fortemente influenciada pela forçante de maré. / The aim of this study was simulate the hydrodynamic of the Inner Continental Shelf of the State of São Paulo (PCISP) and of the Mid Continental Shelf of the State of São Paulo (PCMSP) during summer, in response to the density gradient forcing, to the climatological wind shear stress forcing and to the tide forcing, applying the tridimensional hydrodynamic numeric model Regional Ocean Modeling System (ROMS). The experiments performed showed the effects of the density distribution over the general circulation behavior in the PCISP and PCMSP are secondary compared with the induced climatological wind shear stress circulation. The results indicate that in the PCISP and in the PCMSP the component velocity parallel to the coast is dominated by subinertial frequencies forcing, as the climatological wind and the density gradient, while the component velocity perpendicular to the coast is strongly influenced by the tide forcing.

人口在空間上分布的差異形成集中發展抑或分散發展型態，相對地對於地方財政的支出亦有不同程度的影響。在現今台灣省各地方政府普遍存在著財源短絀之情形下，農地釋出政策的實施所造成都市規模的擴張，是否會引發地方財政加重的趨勢，實有深究的必要。因此本研究的目的，乃在於探討都市空間結構的差異對公共支出的變化影響效果，並進一步提出土地發展政策涵義。 　　針對上述，本研究擬藉由人口密度斜率此變數，作為都市空間結構之指標，進而瞭解都市發展型態之差異對地方公共支出的影響。所謂人口密度斜率乃是隨著距離的增加，人口在空間上的變化情形。其次，以中位數投票模型理論及官僚模型理論為基礎，建立模型並進行測試，同時為因應農地釋出政策的實施，在台灣省各市鄉鎮都市計畫區農業區釋出的假設前題下，進行模擬分析。 　　經本研究結果發現，就總體而言，台灣省各市鄉鎮目前之都市空間結構有分散發展的趨勢，並有無效率的現象；次就農地釋出而言，在不考慮人口規模聚集經濟的情況下，過多的土地開發，將會有惡化現存地方財政不足之趨勢。 / The difference of population spreads in the spatial will result in the pattern of concentrated development or dispersed development. Oppo-sitely, the difference pattern will influence to local public expenditures. On the condition that the local government often exists short tag of finance in Taiwan, so to practice policy of agriculture land release which should result in the extension of urban scale whether will increase the final burden or not, has necessary to discuss. Thus, the propose of this study is to discuss that the difference of urban spatial structure has what effect of change influence to pubhc expenditure, and father want to propose the meaning of land development policy. 　　As above that, this study uses the population density gradient to be the guide of urban spatial structure, and then want to understand the difference of urban development pattern has what influence to local public ex-penditure. Population density describes how rapidly the density falls off with distance. Next, based on the median voter theory and bureaucracy theory to built the model and test it, then for to practice the policy of agriculture land release, this study on the assumption that all agriculture area of urban planned area will be released in Taiwan progresses simulation and analysis which wants to know the influence of agriculture land release. 　　According to the result of this study, we find, fister, the present con-dition of local public in Taiwan, urban spatial structure has the tend of dis-persed development, and cause to nonefficiency. Second, if the agriculture land release do not consider the agglomeration economics of population scale, then to development too many lands will worse present local final.

No description available.

No description available.

O trabalho tem como objetivo determinar a influencia da concentração de monoestearato de sorbitano, componente do núcleo oleoso das nanocápsulas, na cinética de liberação do éster etílico de indometacina a partir de nanocápsulas de poli(ε-caprolactona) (PCL). Com este propósito o éster etílico de indometacina foi associado a cada sistema e sua hidrólise alcalina foi realizada para simular uma condição sink. A velocidade de consumo do éster etílico de indometacina foi menor conforme o aumento da concentração do monoestearato de sorbitano. O tempo de meia-vida do consumo do éster etílico de indometacina associado as nanocápsulas foi relacionado com a concentração do monoestearato de sorbitano, sendo maior, enquanto maior a concentração do monoestearato. O mecanismo de liberação foi determinado como sendo transporte anômalo. Foi observada uma relação linear direta entre o aumento da concentração do monoestearato de sorbitano e a concentração de partículas nas suspensões de nanocápsulas (R2=0,9711). Mistura de outras nanopartículas que não as nanocápsulas, foram observadas e caracterizadas. O fluxo difusional do éster a partir das nanocápsulas foi determinado e diminuiu significativamente com o aumento da concentração do monoestearato, devido a mudanças na viscosidade do núcleo das nanocápsulas com o aumento da concentração do monoestearato de sorbitano. Por fim, os resultados demonstraram que o principal fator que contribui para o retardo no tempo para o consumo do éster etílico de indometacina é a relação direta entre a concentração do monoestearato de sorbitano e a permeabilidade das nanocápsulas (R=0,9894). / The aim of this work was to evaluate the influence of the sorbitan monoestearate concentration, one of the components of the oil core of the nanocapsules, in the release kinetic of the indomethacin ethyl ester-loaded poli(ε-caprolactone) nanocapsules. In this way, the indomethacin ethyl ester was entrapped within each system and its alkaline hydrolysis was carried out to simulate a sink condition. The rate for the indomethacin ethyl ester consumption decreased with the increase in sorbitan monostearate concentrations. The indomethacin ethyl ester half-live was related to the sorbitan monostearate concentration, increasing as the sorbitan monostearate concentration increased. The drug release mechanism was determined as anomalous transport. Linear correlations were obtained between the increase in the sorbitan monostearate concentration and the particles concentration in the suspensions (R2 = 0.9711). Mixture of different nanoparticles that are not nanocapsules were observed by density gradient and characterized. The indomethacin ethyl ester fluxes from the nanocapsules were determined and presented a decrease of the flux as the sorbitan monostearate concentration increased. This result was related to changes in the oil core viscosity caused by the variation of the sorbitan monostearate concentration. Finally, the results demonstrated that the main factor that contributes for the delaying in the time for the indometahcin ethyl ester consumption was the direct relation between the sorbitan monostearate concentration and the apparent permeability of the nanocapsules (R2 = 0.9894).

O trabalho tem como objetivo determinar a influencia da concentração de monoestearato de sorbitano, componente do núcleo oleoso das nanocápsulas, na cinética de liberação do éster etílico de indometacina a partir de nanocápsulas de poli(ε-caprolactona) (PCL). Com este propósito o éster etílico de indometacina foi associado a cada sistema e sua hidrólise alcalina foi realizada para simular uma condição sink. A velocidade de consumo do éster etílico de indometacina foi menor conforme o aumento da concentração do monoestearato de sorbitano. O tempo de meia-vida do consumo do éster etílico de indometacina associado as nanocápsulas foi relacionado com a concentração do monoestearato de sorbitano, sendo maior, enquanto maior a concentração do monoestearato. O mecanismo de liberação foi determinado como sendo transporte anômalo. Foi observada uma relação linear direta entre o aumento da concentração do monoestearato de sorbitano e a concentração de partículas nas suspensões de nanocápsulas (R2=0,9711). Mistura de outras nanopartículas que não as nanocápsulas, foram observadas e caracterizadas. O fluxo difusional do éster a partir das nanocápsulas foi determinado e diminuiu significativamente com o aumento da concentração do monoestearato, devido a mudanças na viscosidade do núcleo das nanocápsulas com o aumento da concentração do monoestearato de sorbitano. Por fim, os resultados demonstraram que o principal fator que contribui para o retardo no tempo para o consumo do éster etílico de indometacina é a relação direta entre a concentração do monoestearato de sorbitano e a permeabilidade das nanocápsulas (R=0,9894). / The aim of this work was to evaluate the influence of the sorbitan monoestearate concentration, one of the components of the oil core of the nanocapsules, in the release kinetic of the indomethacin ethyl ester-loaded poli(ε-caprolactone) nanocapsules. In this way, the indomethacin ethyl ester was entrapped within each system and its alkaline hydrolysis was carried out to simulate a sink condition. The rate for the indomethacin ethyl ester consumption decreased with the increase in sorbitan monostearate concentrations. The indomethacin ethyl ester half-live was related to the sorbitan monostearate concentration, increasing as the sorbitan monostearate concentration increased. The drug release mechanism was determined as anomalous transport. Linear correlations were obtained between the increase in the sorbitan monostearate concentration and the particles concentration in the suspensions (R2 = 0.9711). Mixture of different nanoparticles that are not nanocapsules were observed by density gradient and characterized. The indomethacin ethyl ester fluxes from the nanocapsules were determined and presented a decrease of the flux as the sorbitan monostearate concentration increased. This result was related to changes in the oil core viscosity caused by the variation of the sorbitan monostearate concentration. Finally, the results demonstrated that the main factor that contributes for the delaying in the time for the indometahcin ethyl ester consumption was the direct relation between the sorbitan monostearate concentration and the apparent permeability of the nanocapsules (R2 = 0.9894).