13 resultados para 060309 Phylogeny and Comparative Analysis

em Helda - Digital Repository of University of Helsinki


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Democratic Legitimacy and the Politics of Rights is a research in normative political theory, based on comparative analysis of contemporary democratic theories, classified roughly as conventional liberal, deliberative democratic and radical democratic. Its focus is on the conceptual relationship between alternative sources of democratic legitimacy: democratic inclusion and liberal rights. The relationship between rights and democracy is studied through the following questions: are rights to be seen as external constraints to democracy or as objects of democratic decision making processes? Are individual rights threatened by public participation in politics; do constitutionally protected rights limit the inclusiveness of democratic processes? Are liberal values such as individuality, autonomy and liberty; and democratic values such as equality, inclusion and popular sovereignty mutually conflictual or supportive? Analyzing feminist critique of liberal discourse, the dissertation also raises the question about Enlightenment ideals in current political debates: are the universal norms of liberal democracy inherently dependent on the rationalist grand narratives of modernity and incompatible with the ideal of diversity? Part I of the thesis introduces the sources of democratic legitimacy as presented in the alternative democratic models. Part II analyses how the relationship between rights and democracy is theorized in them. Part III contains arguments by feminists and radical democrats against the tenets of universalist liberal democratic models and responds to that critique by partly endorsing, partly rejecting it. The central argument promoted in the thesis is that while the deconstruction of modern rationalism indicates that rights are political constructions as opposed to externally given moral constraints to politics, this insight does not delegitimize the politics of universal rights as an inherent part of democratic institutions. The research indicates that democracy and universal individual rights are mutually interdependent rather than oppositional; and that democracy is more dependent on an unconditional protection of universal individual rights when it is conceived as inclusive, participatory and plural; as opposed to robust majoritarian rule. The central concepts are: liberalism, democracy, legitimacy, deliberation, inclusion, equality, diversity, conflict, public sphere, rights, individualism, universalism and contextuality. The authors discussed are e.g. John Rawls, Jürgen Habermas, Seyla Benhabib, Iris Young, Chantal Mouffe and Stephen Holmes. The research focuses on contemporary political theory, but the more classical work of John S. Mill, Benjamin Constant, Isaiah Berlin and Hannah Arendt is also included.

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This work is concerned with presenting a modified theoretical approach to the study of centre-periphery relations in the Russian Federation. In the widely accepted scientific discourse, the Russian federal system under the Yeltsin Administration (1991-2000) was asymmetrical; largely owing to the varying amount of structural autonomy distributed among the federation s 89 constituent units. While providing an improved understanding as to which political and socio-economic structures contributed to federal asymmetry, it is felt that associated large N-studies have underemphasised the role played by actor agency in re-shaping Russian federal institutions. It is the main task of this thesis to reintroduce /re-emphasise the importance of actor agency as a major contributing element of institutional change in the Russian federal system. By focusing on the strategic agency of regional elites simultaneously within regional and federal contexts, the thesis adopts the position that political, ethnic and socio-economic structural factors alone cannot fully determine the extent to which regional leaders were successful in their pursuit of economic and political pay-offs from the institutionally weakened federal centre. Furthermore, this work hypothesises that under conditions of federal institutional uncertainty, it is the ability of regional leaders to simultaneously interpret various mutable structural conditions then translate them into plausible strategies which accounts for the regions ability to extract variable amounts of economic and political pay-offs from the Russian federal system. The thesis finds that while the hypothesis is accurate in its theoretical assumptions, several key conclusions provide paths for further inquiry posed by the initial research question. First, without reliable information or stable institutions to guide their actions, both regional and federal elites were forced into ad-hoc decision-making in order to maintain their core strategic focus: political survival. Second, instead of attributing asymmetry to either actor agency or structural factors exclusively, the empirical data shows that both agency and structures interact symbiotically in the strategic formulation process, thus accounting for the sub-optimal nature of several of the actions taken in the adopted cases. Third, as actor agency and structural factors mutate over time, so, too do the perceived payoffs from elite competition. In the case of the Russian federal system, the stronger the federal centre became, the less likely it was that regional leaders could extract the high degree of economic and political pay-offs that they clamoured for earlier in the Yeltsin period. Finally, traditional approaches to the study of federal systems which focus on institutions as measures of federalism are not fully applicable in the Russian case precisely because the institutions themselves were a secondary point of contention between competing elites. Institutional equilibriums between the regions and Moscow were struck only when highly personalised elite preferences were satisfied. Therefore the Russian federal system is the product of short-term, institutional solutions suited to elite survival strategies developed under conditions of economic, political and social uncertainty.

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We investigate methods for recommending multimedia items suitable for an online multimedia sharing community and introduce a novel algorithm called UserRank for ranking multimedia items based on link analysis. We also take the initiative of applying EigenRumor from the domain of blogosphere to multimedia. Furthermore, we present a strategy for making personalized recommendation that combines UserRank with collaborative filtering. We evaluate our method with an informal user study and show that results obtained are promising.

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Autoimmune diseases are a major health problem. Usually autoimmune disorders are multifactorial and their pathogenesis involves a combination of predisposing variations in the genome and other factors such as environmental triggers. APECED (autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy) is a rare, recessively inherited, autoimmune disease caused by mutations in a single gene. Patients with APECED suffer from several organ-specific autoimmune disorders, often affecting the endocrine glands. The defective gene, AIRE, codes for a transcriptional regulator. The AIRE (autoimmune regulator) protein controls the expression of hundreds of genes, representing a substantial subset of tissue-specific antigens which are presented to developing T cells in the thymus and has proven to be a key molecule in the establishment of immunological tolerance. However, the molecular mechanisms by which AIRE mediates its functions are still largely obscure. The aim of this thesis has been to elucidate the functions of AIRE by studying the molecular interactions it is involved in by utilizing different cultured cell models. A potential molecular mechanism for exceptional, dominant, inheritance of APECED in one family, carrying a glycine 228 to tryptophan (G228W) mutation, was described in this thesis. It was shown that the AIRE polypeptide with G228W mutation has a dominant negative effect by binding the wild type AIRE and inhibiting its transactivation capacity in vitro. The data also emphasizes the importance of homomultimerization of AIRE in vivo. Furthermore, two novel protein families interacting with AIRE were identified. The importin alpha molecules regulate the nuclear import of AIRE by binding to the nuclear localization signal of AIRE, delineated as a classical monopartite signal sequence. The interaction of AIRE with PIAS E3 SUMO ligases, indicates a link to the sumoylation pathway, which plays an important role in the regulation of nuclear architecture. It was shown that AIRE is not a target for SUMO modification but enhances the localization of SUMO1 and PIAS1 proteins to nuclear bodies. Additional support for the suggestion that AIRE would preferably up-regulate genes with tissue-specific expression pattern and down-regulate housekeeping genes was obtained from transactivation studies performed with two models: human insulin and cystatin B promoters. Furthermore, AIRE and PIAS activate the insulin promoter concurrently in a transactivation assay, indicating that their interaction is biologically relevant. Identification of novel interaction partners for AIRE provides us information about the molecular pathways involved in the establishment of immunological tolerance and deepens our understanding of the role played by AIRE not only in APECED but possibly also in several other autoimmune diseases.

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Increasing concern about global climate warming has accelerated research into renewable energy sources that could replace fossil petroleum-based fuels and materials. Bioethanol production from cellulosic biomass by fermentation with baker s yeast Saccharomyces cerevisiae is one of the most studied areas in this field. The focus has been on metabolic engineering of S. cerevisiae for utilisation of the pentose sugars, in particular D-xylose that is abundant in the hemicellulose fraction of biomass. Introduction of a heterologous xylose-utilisation pathway into S. cerevisiae enables xylose fermentation, but ethanol yield and productivity do not reach the theoretical level. In the present study, transcription, proteome and metabolic flux analyses of recombinant xylose-utilising S. cerevisiae expressing the genes encoding xylose reductase (XR) and xylitol dehydrogenase (XDH) from Pichia stipitis and the endogenous xylulokinase were carried out to characterise the global cellular responses to metabolism of xylose. The aim of these studies was to find novel ways to engineer cells for improved xylose fermentation. The analyses were carried out from cells grown on xylose and glucose both in batch and chemostat cultures. A particularly interesting observation was that several proteins had post-translationally modified forms with different abundance in cells grown on xylose and glucose. Hexokinase 2, glucokinase and both enolase isoenzymes 1 and 2 were phosphorylated differently on the two different carbon sources studied. This suggests that phosphorylation of glycolytic enzymes may be a yet poorly understood means to modulate their activity or function. The results also showed that metabolism of xylose affected the gene expression and abundance of proteins in pathways leading to acetyl-CoA synthesis and altered the metabolic fluxes in these pathways. Additionally, the analyses showed increased expression and abundance of several other genes and proteins involved in cellular redox reactions (e.g. aldo-ketoreductase Gcy1p and 6-phosphogluconate dehydrogenase) in cells grown on xylose. Metabolic flux analysis indicated increased NADPH-generating flux through the oxidative part of the pentose phosphate pathway in cells grown on xylose. The most importantly, results indicated that xylose was not able to repress to the same extent as glucose the genes of the tricarboxylic acid and glyoxylate cycles, gluconeogenesis and some other genes involved in the metabolism of respiratory carbon sources. This suggests that xylose is not recognised as a fully fermentative carbon source by the recombinant S. cerevisiae that may be one of the major reasons for the suboptimal fermentation of xylose. The regulatory network for carbon source recognition and catabolite repression is complex and its functions are only partly known. Consequently, multiple genetic modifications and also random approaches would probably be required if these pathways were to be modified for further improvement of xylose fermentation by recombinant S. cerevisiae strains.

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In the present study, we identified a novel asthma susceptibility gene, NPSR1 (neuropeptide S receptor 1) on chromosome 7p14.3 by the positional cloning strategy. An earlier significant linkage mapping result among Finnish Kainuu asthma families was confirmed in two independent cohorts: in asthma families from Quebec, Canada and in allergy families from North Karelia, Finland. The linkage region was narrowed down to a 133-kb segment by a hierarchial genotyping method. The observed 77-kb haplotype block showed 7 haplotypes and a similar risk and nonrisk pattern in all three populations studied. All seven haplotypes occur in all three populations at frequences > 2%. Significant elevated relative risks were detected for elevated total IgE (immunoglobulin E) or asthma. Risk effects of the gene variants varied from 1.4 to 2.5. NPSR1 belongs to the G protein-coupled receptor (GPCR) family with a topology of seven transmembrane domains. NPSR1 has 9 exons, with the two main transcripts, A and B, encoding proteins of 371 and 377 amino acids, respectively. We detected a low but ubiquitous expression level of NPSR1-B in various tissues and endogenous cell lines while NPSR1-A has a more restricted expression pattern. Both isoforms were expressed in the lung epithelium. We observed aberrant expression levels of NPSR1-B in smooth muscle in asthmatic bronchi as compared to healthy. In an experimental mouse model, the induced lung inflammation resulted in elevated Npsr1 levels. Furthermore, we demonstrated that the activation of NPSR1 with its endogenous agonist, neuropeptide S (NPS), resulted in a significant inhibition of the growth of NPSR1-A overexpressing stable cell lines (NPSR1-A cells). To determine which target genes were regulated by the NPS-NPSR1 pathway, NPSR1-A cells were stimulated with NPS, and differentially expressed genes were identified using the Affymetrix HGU133Plus2 GeneChip. A total of 104 genes were found significantly up-regulated and 42 down-regulated 6 h after NPS administration. The up-regulated genes included many neuronal genes and some putative susceptibility genes for respiratory disorders. By Gene Ontology enrichment analysis, the biological process terms, cell proliferation, morphogenesis and immune response were among the most altered. The expression of four up-regulated genes, matrix metallopeptidase 10 (MMP10), INHBA (activin A), interleukin 8 (IL8) and EPH receptor A2 (EPHA2), were verified and confirmed by quantitative reverse-transcriptase-PCR. In conclusion, we identified a novel asthma susceptibility gene, NPSR1, on chromosome 7p14.3. NPS-NPSR1 represents a novel pathway that regulates cell proliferation and immune responses, and thus may have functional relevance in the pathogenesis of asthma.

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Central and East European countries have faced a difficult process of transition since the dissolution of the Soviet bloc. Ten transition countries (Hungary, Poland, teh Czech Republic, Slovakia, Slovenia, Lithuania, Latvia, Estonia, Bulgaria and Romania have chosen to join the EU and have moulded their transition reforms to ensure the compliance of their legal and institutional framework with EU requirements. The high levels of FDI attracted by the candidate countries for EU membership had been attributed to rapid transition of the countries aiming to join the European Union and the fact that favourable evaluations by EU authorities of the progress made by the candidates had a large impact on improving investor confidence. The aim of this paper is to investigate the reform strategies of the Czech Republic and Slovakia undertaken when the countries were preparing for EU membership and the dynamics of FDI inflows into these economies. Subsequently a comparative analysis of FDI stocks in these countries is conducted. We find that both countries faced similar economic challenges in implementing structural and institutional reforms. In accordance with EU requirements the Czech Republic and Slovakia have perfected their legal and institutional framework, increased the authority of regulatory and supervisory bodies and focused on implementation of new or amended legislation. During the period of the analysis (1998 - 2007) the Czech Republic and Slovakia have attracted increasing amounts of FDI. Comparative analysis in terms of important determinants of FDI reveals further similar features: macroeconomic stability; an open and liberalised market; low labour costs compared to EU-15 and a similar breakdown of FDI inflows by investor country. Consequently, the fact that the Czech Republic received much larger volumes of net FDI inflows could be attributed to the difference in market size between the two states. This conclusion is consistent with previous empirical studies that list market size among the main determinants of FDI. However, when we look at FDI as a percentage of GDP the evidence is more mixed. In 2004 - 2007, Slovakia has surpassed the Czech Republic twice. Whether this tendency will persist remains to be seen. The analysis in this paper based on empirical data. However, the choice of the method, namely case studies and comparative analysis, means that the conclusions of this study are theoretical and remain to be further tested in quantitative models.