Endosomes are dynamic vesicular structures which transport cargo molecules internalized into the cell via endocytosis. Endosomal trafficking of cargo involves a large number of individual endosomes that regularly interact with each other via fusion and fission and thus form a dynamic network wherein endocytosed cargo is sorted and transported to various other intracellular compartments. In this study we present a general theoretical framework that takes into account individual endosomes and several key microscopic interaction processes among them. By combining theory with quantitative experiments, we seek to address the fundamental question of how the behaviour of the endosomal network emerges from the interactions among many individual endosomes of different sizes and cargo contents. Our theory is based on distributions of endosomes of various sizes and cargo amount. We compare our theory to experimental time course distributions of LDL, a degradative cargo, in a population of early endosomes. Early endosomes display a broad distribution of cargo with a characteristic power law, which we show is a consequence of stochastic fusion events of cargo carrying early endosomes. A simple model can quantitatively describe time-dependent statistics of LDL distributions in individual early endosomes. From fits of the theory to experimental data we can determine key parameters of endosomal trafficking such as the endosome fusion rate and the fluxes of cargo into and out of the network. Our theory predicts several experimentally confirmed scaling behaviours, which arise as a result of endosome fusion. Our theory provides a link between the dynamics at individual endosome level and average properties of the endosomal network. We show from our theory that some features of the endosomal distributions, which arise from interactions among individual endosomes, are sensitive to alterations in chosen parameters. This provides a direct means to study perturbation experiments wherein the cargo distribution can vary in response to changes of the endocytic system. Our analysis provides a powerful tool for the study of genetic and chemical perturbations that may alter specific systems properties and for extracting various kinetic rates involved in endosomal trafficking from only still images at different points.

Made available in DSpace on 2014-12-17T14:20:13Z (GMT). No. of bitstreams: 1 ElizaMAV.pdf: 1730672 bytes, checksum: 35e40a54bb83db5cd0a3a5dcdde9994a (MD5) Previous issue date: 2009-06-15 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / The study made in this thesis analyzes the new form of work organization at the urban collective transportation sector, so called Altemative Transportation which is a new form of public transportation that appears in the Brazilian urban context by the mid ninety' s, this work is made by independent or sub-contracted workers, usually organized in cooperatives . It reflects the investigation of new forms of precarious work, unformal which has been expanding in the urban transportation sector. Thus, discusses non regulation of the services sector problem the ways of survival of exc1uded workers from the formal work market mainly afier the capital productive restructure. It has as privileged area of investigation, the sector policy of urban transportation that make field of the main nets of political articulations that define the dynamic of the urban space. It is known that the urban collective transportation allows the access to the production, circulation and general consumption being necessary to the mobility of the resident population, mainly to those with low purchasing capacity. It becomes a field of empirical investigation at the Belem municipal, located at the Amazonic region - north Brazil. The main points dealed on this research start from concrete relations from the daily life of workers that deve1op their activity on the altemative transport mediated with theoretical references needed for understanding and interpretation of the studied reality. The investigation strategies were built from the abstract (theorical knowledge produced for the reality analyze) in concrete by the investigation quantitative-qualitative from this area of urban policy, making up possible the formation of a references chart to the analyses of the studied subject. Rescue his historicity, from characterization of the urban space of the metropolitan region of Belem passing true the forms of organization and urban services performances while essential production and reproduction element of the social relations. Identifies the main individuals that historically have been participating in the construction of the municipality transport policy and the ways of expression of the local political strength relations. Outstand the State paper on the net of established relations near the local power, as well as outstand the importance of social sciences in the understanding of urban policies in the transportation area, trying to bring input to the academicals -scientific debate .The above e1ected and mentioned points in this study are crucial for a critical reflection of the transportation policies. That relation is not given, but historically built at the power relation chart that makes up this unique area of the urban policies / O estudo realizado nesta tese analisa as novas formas de organiza??o do trabalho no setor de transporte coletivo urbano, o chamado Transporte Alternativo que ? uma nova modalidade de transporte p?blico que surge nos contextos urbanos brasileiro nos meados da d?cada de noventa, cuja presta??o do servi?o ? operacionalizado por trabalhadores aut?nomos ou subcontratado, em geral organizado em cooperativas. Trata-se de investiga??o das novas formas de trabalho prec?rio, informal que vem se expandindo no setor de transporte urbano. Portanto, discute a desregulamenta??o do setor de servi?os e problematiza as formas de sobreviv?ncia de trabalhadores exclu?dos do mercado formal de trabalho principalmente a partir da reestrutura??o produtiva do capital. Tem como ?rea privilegiada de investiga??o, a pol?tica setorial de transporte urbano que constitu? campo das principais redes de articula??es pol?ticas definidoras da din?mica do espa?o urbano. Sabe-se que o transporte coletivo urbano possibilita o acesso ? produ??o, circula??o e consumo em geral, sendo necess?rio ? mobilidade da popula??o residente, principalmente aquela de baixo poder aquisitivo. Toma-se como campo de investiga??o emp?rica o Munic?pio de Bel?m, localizado na Regi?o Amaz?nica - Norte do Brasil. Os pontos principais tratados nesta pesquisa partem das rela??es concretas do cotidiano de trabalhadores que desenvolvem sua atividade no Transporte Alternativo mediados com referenciais te?ricos necess?rios ? compreens?o e interpreta??o da realidade estudada. As estrat?gias de investiga??o foram constru?das do abstrato (conhecimentos te?rico produzidos para an?lise da realidade) ao concreto atrav?s da investiga??o quantitativo-qualitativa desta ?rea das pol?ticas urbanas, possibilitando a forma??o de um quadro de referencias para a an?lise do objeto estudado. Resgata a sua historicidade, a partir da caracteriza??o do espa?o urbano da Regi?o Metropolitana de Bel?m perpassando pelas formas de organiza??o e presta??o de servi?o de transporte enquanto elemento essencial de produ??o e reprodu??o das rela??es sociais. Identifica os principais sujeitos que historicamente vem participando da constru??o da pol?tica de transporte municipal e a formas de express?o das rela??es de for?as pol?ticas local. Destaca o papel do Estado na rede de rela??es estabelecidas junto ao poder local, bem como destaca a import?ncia das Ci?ncias Sociais no entendimento das pol?ticas urbanas na ?rea de transporte, buscando trazer contribui??es para pra o debate acad?mico-cient?fico. Os pontos mencionados e elegidos neste estudo s?o fundamentais a uma reflex?o cr?tica da pol?tica de transporte. Essa rela??o n?o ? dada, mas constru?da historicamente no quadro de rela??es de for?as que comp?em esta ?rea privilegiada das pol?ticas urbanas

In Germany, many universities have student tickets that are bargained for between student representatives and public transport companies, approved by referendum, and mandatory for all students. They allow the use of public transport at no additional cost. I analyze such a scenario in a theoretical model as an example of a flat-rate ticket for public transport which is implemented by majority decision. The mandatory character of the ticket reduces transaction costs like marketing and ticket inspection, reducing the ticket price and thus the students’ commuting expenses. However, there is a countervailing effect. Students face and rationally expect zero marginal monetary commuting costs, so that new students choose a place of residence which is relatively far from the university. This in turn raises the equilibrium ticket price. It may even be the case that students would be better off if such a ticket had never existed. Nonetheless, they always vote for it in referenda, because accepting the high price is optimal given their place of residence. After laying out the model, I analyze an optimal policy, which consists, for example, of subsidizing student dorms at an efficient distance to the city center.