This diploma thesis is part of a project aiming for the development of low molecular compounds which would be capable to inhibit the interaction between human transcription factor FOXO3 and DNA. Main goal of this thesis is the characterization of the interaction between the low molecular inhibitor S9 and the DNA-binding domain of FOXO3 protein (FOXO3-DBD) by using variety of biophysical methods such as NMR, microscale thermophoresis and native electrophoresis. FOXO transcription factors are important and evolutionary conserved regulatory proteins, which are involved in many crucial cellular processes. The activity of FOXO proteins is regulated by posttranslational modifications, out of which the most important are phosphorylation, acetylation and ubiquitination. Forkhead transcription factors participate in a variety of different cellular functions and are part of several signaling pathways. Its expression might be tissue specific. They contain approximately 100 amino acids long DNA- binding domain composed of several parts. Among its main functions belong the regulation of cell cycle and apoptosis, proliferation and cell differentiation, metabolism control and stress- response regulation. Tumor cells of lymfoblastome have developed resistance against chemotherapy by increasing activity of FOXO3...

<p>The purpose of this study was to develop a recursive algorithm for computing a maximum a posteriori (MAP) estimate of a binary Markov random field (MRF) by using the MAP-MRF framework. We also discuss how to include an approximation in the recursive scheme, so that the algorithm becomes computationally feasible also for larger problems. In particular, we discuss how our algorithm can be used in an image analysis setting. We consider a situation where an unobserved latent field is assumed to follow a Markov random field prior model, a Gaussian noise-corrupted version of the latent field is observed, and we estimate the unobserved field by the MAP estimator.</p>

<p>Based on the tumor growth model of Harald Weedon-Fekjær et al.'s paper "Breast cancer tumor growth estimated through mammography screening data", a simulation of breast cancer occurrence and tumor growth in a large population of women was made. The simulation was made realistic by starting tumor growth according to a Poisson process, including a distribution for clinical detection size and a screening test sensitivity function, and using an individual growth rate, based on estimates of Weedon-Fekjær et al. After running the full simulation, parts of the simulation outcomes were compared to known data of breast cancer and the model was found to give realistic and expected results. The simulation was then used to look for other interesting results such as expected reduction in time to tumor detection due to screening and finding the size distribution of tumors before and after screening. For the age group 50 - 69 years, it was found that screening every year allows a reduction of 19.1 months, while screening every two, three, five and ten years allows for reductions of, respectively, 9.5, 8.3, 6.1 and 3.4 months. These results are based on the assumption that tumors are actually found at screening, i.e. the tumors are not found clinically before they are found on screening. When clinical findings are included, different results are obtained. For the age group 50 - 69 years, it was found that screening every year allows a reduction of 15 months, while screening every two, three, five and ten years allows for reductions of, respectively, 4.8, 1.4, -5.6 and -21.5 months. Negative numbers indicate that a tumor is found earlier clinically than at screening.</p>

Based on the tumor growth model of Harald Weedon-Fekjær et al.'s paper "Breast cancer tumor growth estimated through mammography screening data", a simulation of breast cancer occurrence and tumor growth in a large population of women was made. The simulation was made realistic by starting tumor growth according to a Poisson process, including a distribution for clinical detection size and a screening test sensitivity function, and using an individual growth rate, based on estimates of Weedon-Fekjær et al. After running the full simulation, parts of the simulation outcomes were compared to known data of breast cancer and the model was found to give realistic and expected results. The simulation was then used to look for other interesting results such as expected reduction in time to tumor detection due to screening and finding the size distribution of tumors before and after screening. For the age group 50 - 69 years, it was found that screening every year allows a reduction of 19.1 months, while screening every two, three, five and ten years allows for reductions of, respectively, 9.5, 8.3, 6.1 and 3.4 months. These results are based on the assumption that tumors are actually found at screening, i.e. the tumors are not found clinically before they are found on screening. When clinical findings are included, different results are obtained. For the age group 50 - 69 years, it was found that screening every year allows a reduction of 15 months, while screening every two, three, five and ten years allows for reductions of, respectively, 4.8, 1.4, -5.6 and -21.5 months. Negative numbers indicate that a tumor is found earlier clinically than at screening.

The purpose of this study was to develop a recursive algorithm for computing a maximum a posteriori (MAP) estimate of a binary Markov random field (MRF) by using the MAP-MRF framework. We also discuss how to include an approximation in the recursive scheme, so that the algorithm becomes computationally feasible also for larger problems. In particular, we discuss how our algorithm can be used in an image analysis setting. We consider a situation where an unobserved latent field is assumed to follow a Markov random field prior model, a Gaussian noise-corrupted version of the latent field is observed, and we estimate the unobserved field by the MAP estimator.

With the first generation of microarray experiments there were discussions and important arguments on how the samples should be treated. This included what kind of transformation and normalization procedures that the data should be subjected to before the actual analysis. With the new generation of microarray experiments, genome wide association studies, and more complicated experiments, new questions and standards arises. An important question is the appropriate use of controls, and what effect these controls have on the assessed behaviour of the genes.The main objective in this thesis was to analyse a data set and experimental procedure from an experiment done at IKM (NTNU, 2009), where the effect of a gastrin treatment was measured on a set of genes along with an unstimulated control sample over a time interval. The experiment was replicated once, giving two independent experiments. A natural extension of this is then; what is the gain in precision by adding additional replicas to the experiment? And what additional information is given in an unstimulated control sample?Our approach was to use the Linear Mixed Effects (LME) framework to fit a regression curve to each gene, for both the treated time series itself, and the treated adjusted for by the unstimulated control sample. Each replication was assumed to have a random offset from the common mean. The mean was modelled using basis expansion with the Legendre polynomials, thus allowing it to vary as a smooth function over the time interval.A computer simulation showed that an increase in the number of independent time series sampled would decrease the error in the estimated expression profile. Even when this causes the number of time points (measurements) within the time series to decrease.The analysis of the data showed that not using an unstimulated control gave many false positive results, however, always using such a control will also cause an increase in both false negative and false positive results, due to increase in stochastisity. However, having an unstimulated control sample will give the researcher an increased control when assessing the effect of the treatment.

In this thesis we have explored the very high prices that sometimes occurs in the Nord Pool electricity market Elspot. By applying AR-GARCH time series models, extreme value theory, and ACER estimation techniques, we have sought to estimate the probabilities of threshold exceedances related to electricity prices. Of particular concern was the heavy-tailed Fr&#233;chet distribution, which was the asymptotic distribution assumed in the ACER estimation.We have found that with extreme value theory we are better equipped to deal with the very high quantiles in the time series we have analyzed. We have also described a method that can give an assessment of the probability of exceeding a selected level in the electricity price.

Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Ciências Agrárias. Programa de Pós-Graduação em Agroecossistemas. / Made available in DSpace on 2012-10-22T18:46:52Z (GMT). No. of bitstreams: 1 241087.pdf: 286194 bytes, checksum: 4d5c466834dc94245c65a205df784d74 (MD5) / O trabalho se propõe a examinar o conteúdo das concepções e práticas de ensino vinculadas ao Movimento dos Trabalhadores Rurais Sem Terra, bem como seu efeito na formação de jovens agricultores que freqüentam um curso de ensino médio conduzido pelo MST comparativamente ao ensino oferecido por uma Escola Técnica Federal, ambos no estado do Rio Grande do Sul. Foram realizadas entrevistas para avaliar em que grau os dois grupos conhecem e estão comprometidos com um ensino orientado pela agroecologia, bem como se o ensino ao qual são submetidos são capazes de transformar sua visão de mundo em direção a práticas produtivas não agressivas ao ambiente e à sociedade. Conclui que a ação pedagógica levada pelo MST é bastante diferenciada do ensino convencional; sua concepção tende a dotar os estudantes de uma visão bem mais crítica quanto aos processos produtivos organizados em torno da Revolução Verde, bem como os induz a assumir uma postura igualmente crítica e transformadora da realidade.

Este estudo foi realizado junto a um grupo de nove famílias de um assentamento do Movimento dos Trabalhadores Rurais Sem Terra (MST), em Rondônia. Estas famílias organizam o trabalho e a vida de forma coletiva há mais de dez anos, em torno do Grupo Coletivo 14 de Agosto. Teve como objetivo compreender as vicissitudes do processo organizativo cotidiano desta experiência e os sentidos de trabalho e de vida que vem sendo construídos a partir dela. De inspiração etnográfica, essa pesquisa tomou o cotidiano como horizonte de visibilidade que permitiu entender o processo de coletivização. O cotidiano é entendido enquanto o espaço onde se dá a vida e a ação social (SATO & SOUZA, 2001; SPINK, 2008). Composto basicamente por militantes do MST e do Movimento dos Pequenos Agricultores (MPA), já nos primeiros anos de acampamento estas famílias começaram a desenvolver práticas de cooperação agrícola e reciprocidade. Depois de significativos experimentos, o grupo resolveu coletivizar definitivamente a terra e trabalhar em sistema de autogestão em todos os setores de produção agrícola. Para dar concretude a essa proposta, sentiram necessidade de coletivizar também parte do trabalho doméstico, passando a ter uma cozinha coletiva. Orientados por uma matriz camponesa e agroecológica, terras, trabalho e cozinha (enquanto espaço de sociabilidade e de trabalho) compõem o tripé que sustenta diariamente a existência do Grupo Coletivo 14 de Agosto. Terras para trabalhar, trabalho livre e associado e a reorganização da vida em torno de uma sociabilidade construída a partir de uma vivência coletiva anticapitalista. Trata-se, nesse sentido, de uma experiência contra-hegemônica que disputa os sentidos da vida e do trabalho na sociedade capitalista por meio de um projeto político profundamente enraizado no cotidiano / This study was carried out among a group of nine families of a settlement of the Movement of Landless Rural Workers (MST ), in Rondônia. These families organize work and life collectively for over ten years around the \"Group Collective August 14\". Aimed at understanding the vicissitudes of everyday organizational process this experience and ways of work and life has been built from it. Inspired in ethnography, this research took everyday life as a horizon of visibility that allowed to understand the process of collectivization. Everyday life is understood as the space where life and social action happens ( SATO & SOUZA , 2001; SPINK , 2008) . Composed primarily by MST militants and the Small Farmers Movement (MPA), since early in camp these families have begun to develop practical agricultural cooperation and reciprocity. After significant experimentations, the group decided definitely collectivize the land and work on self-management in all sectors of work. To give concreteness to this proposal, also felt the need to collectivize domestic work, going to have a collective kitchen. Guided by a matrix and agroecological peasant, land, work and kitchen (as a space of sociability and work) make up the tripod that supports the daily existence of the \"Group Collective August 14\". Lands to work, free and associated labor and the reorganization of life around a sociability constructed from an anti-capitalist collective experience. It is, accordingly, an experience counter-hegemonic that fights the way of life and work in capitalist society through a political project deeply rooted in the everyday life

Este estudo foi realizado junto a um grupo de nove famílias de um assentamento do Movimento dos Trabalhadores Rurais Sem Terra (MST), em Rondônia. Estas famílias organizam o trabalho e a vida de forma coletiva há mais de dez anos, em torno do Grupo Coletivo 14 de Agosto. Teve como objetivo compreender as vicissitudes do processo organizativo cotidiano desta experiência e os sentidos de trabalho e de vida que vem sendo construídos a partir dela. De inspiração etnográfica, essa pesquisa tomou o cotidiano como horizonte de visibilidade que permitiu entender o processo de coletivização. O cotidiano é entendido enquanto o espaço onde se dá a vida e a ação social (SATO & SOUZA, 2001; SPINK, 2008). Composto basicamente por militantes do MST e do Movimento dos Pequenos Agricultores (MPA), já nos primeiros anos de acampamento estas famílias começaram a desenvolver práticas de cooperação agrícola e reciprocidade. Depois de significativos experimentos, o grupo resolveu coletivizar definitivamente a terra e trabalhar em sistema de autogestão em todos os setores de produção agrícola. Para dar concretude a essa proposta, sentiram necessidade de coletivizar também parte do trabalho doméstico, passando a ter uma cozinha coletiva. Orientados por uma matriz camponesa e agroecológica, terras, trabalho e cozinha (enquanto espaço de sociabilidade e de trabalho) compõem o tripé que sustenta diariamente a existência do Grupo Coletivo 14 de Agosto. Terras para trabalhar, trabalho livre e associado e a reorganização da vida em torno de uma sociabilidade construída a partir de uma vivência coletiva anticapitalista. Trata-se, nesse sentido, de uma experiência contra-hegemônica que disputa os sentidos da vida e do trabalho na sociedade capitalista por meio de um projeto político profundamente enraizado no cotidiano / This study was carried out among a group of nine families of a settlement of the Movement of Landless Rural Workers (MST ), in Rondônia. These families organize work and life collectively for over ten years around the \"Group Collective August 14\". Aimed at understanding the vicissitudes of everyday organizational process this experience and ways of work and life has been built from it. Inspired in ethnography, this research took everyday life as a horizon of visibility that allowed to understand the process of collectivization. Everyday life is understood as the space where life and social action happens ( SATO & SOUZA , 2001; SPINK , 2008) . Composed primarily by MST militants and the Small Farmers Movement (MPA), since early in camp these families have begun to develop practical agricultural cooperation and reciprocity. After significant experimentations, the group decided definitely collectivize the land and work on self-management in all sectors of work. To give concreteness to this proposal, also felt the need to collectivize domestic work, going to have a collective kitchen. Guided by a matrix and agroecological peasant, land, work and kitchen (as a space of sociability and work) make up the tripod that supports the daily existence of the \"Group Collective August 14\". Lands to work, free and associated labor and the reorganization of life around a sociability constructed from an anti-capitalist collective experience. It is, accordingly, an experience counter-hegemonic that fights the way of life and work in capitalist society through a political project deeply rooted in the everyday life