29 resultados para tumor margins


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A robust pole assignment by linear state feedback is achieved in state-space representation by selecting a feedback which minimises the conditioning of the assigned eigenvalues of the closed-loop system. It is shown here that when this conditioning is minimised, a lower bound on the stability margin in the frequency domain is maximised.

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This article discusses the character of mineral resource governance at the margins of the state in Tanzania and the way artisanal gold miners are incorporated into mineral sector transformation. The landscape of mineral resource exploitation has changed dramatically over the past 20 years: processes of economic liberalisation have heralded massive foreign investment in large-scale gold mining, while also stimulating artisanal activities. Against this background, the article shows how artisanal gold miners are affected by contradictory processes: some have become integrated with state institutions and legal processes, while others, the large majority, are either further excluded or incorporated in ways that exacerbate insecurity and exploitation, underpinned by socio-economic inequalities. These processes are compounded by the actions of large-scale and medium-scale gold mining companies and by poor local governance. It is open to debate whether this will bring improved integration and welfare for artisanal mining communities or new forms of exclusion, although evidence suggests the latter.

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This paper examines the implications of using marketing margins in applied commodity price analysis. The marketing-margin concept has a long and distinguished history, but it has caused considerable controversy. This is particularly the case in the context of analyzing the distribution of research gains in multi-stage production systems. We derive optimal tax schemes for raising revenues to finance research and promotion in a downstream market, derive the rules for efficient allocation of the funds, and compare the rules with an without the marketing-margin assumption. Applying the methodology to quarterly time series on the Australian beef-cattle sector and, with several caveats, we conclude that, during the period 1978:2 - 1988:4, the Australian Meat and Livestock Corporation optimally allocated research resources.

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The crisis of the national project in the early 1990s, caused by a short-lived but disastrous government, led Brazilian art cinema, for the first time, to look at itself as periphery and re-approach the old colonial center, Portugal. Terra estrangeira/Foreign Land (Walter Salles & Daniela Thomas, Brazil/Portugal, 1995), a film about Brazilian exiles in Portugal, is the best illustration of this perspective shift which provides a new sense of Brazil’s scale and position within a global context. Shot mainly on location in São Paulo, Lisbon and Cape Verde, it promotes the encounter of Lusophone peoples who find a common ground in their marginal situation. Rather than as a former empire, Portugal is defined by its situation at the edge of Europe and by beliefs such as Sebastianism, whose origins go back to the time when the country was dominated by Spain. As a result, notions of “core” or “center” are devolved to the realm of myth. The film’s carefully crafted dialogue combines Brazilian, Portuguese and Creole linguistic peculiarities into a common dialect of exclusion, while language puns trigger visual rhymes which refer back to the Cinema Novo (the Brazilian New Wave) repertoire and restage the imaginary of the discovery turned into unfulfilled utopia. The main characters also acquire historical resonances, as they are depicted as descendants of Iberian conquistadors turned into smugglers of precious stones in the present. Their activities define a circuit of international exchange which resonates with that of globalized cinema, a realm in which Foreign Land, made up of citations and homage to other cinemas, tries to retrieve a sense of belonging.

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The crisis of the national project in the early 1990s, caused by a short-lived but disastrous government, led Brazilian art cinema, for the first time, to look at itself as periphery and re-approach the old colonial centre, Portugal. Terra estrangeira/Foreign Land (Walter Salles & Daniela Thomas, Brazil/Portugal, 1995), a film about Brazilian exiles in Portugal, is the best illustration of this perspective shift aimed at providing a new sense of Brazil’s scale and position within a global context. Shot mainly on location in São Paulo, Lisbon and Cape Verde, it promotes the encounter of Lusophone peoples who find a common ground in their marginal situation. Even Portugal is defined by its location at the edge of Europe and by beliefs such as Sebastianism, whose origins go back to the time when the country was dominated by Spain. As a result, notions of ‘core’ or ‘centre’ are devolved to the realm of myth. The film’s carefully crafted dialogues combine Brazilian, Portuguese and Creole linguistic peculiarities into a common dialect of exclusion, while language puns trigger visual rhymes which refer back to the Cinema Novo (the Brazilian New Wave) repertoire and restage the imaginary of the discovery turned into unfulfilled utopia. The main characters also acquire historical resonances, as they are depicted as descendants of Iberian conquistadors turned into smugglers of precious stones in the present. Their activities define a circuit of international exchange which resonates with that of globalized cinema, a realm in which Foreign Land, made up of citations and homage to other cinemas, tries to retrieve a sense of belonging.

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This article examines the marginal position of artisanal miners in sub-Saharan Africa, and considers how they are incorporated into mineral sector change in the context of institutional and legal integration. Taking the case of diamond and gold mining in Tanzania, the concept of social exclusion is used to explore the consequences of marginalization on people's access to mineral resources and ability to make a living from artisanal mining. Because existing inequalities and forms of discrimination are ignored by the Tanzanian state, the institutionalization of mineral titles conceals social and power relations that perpetuate highly unequal access to resources. The article highlights the complexity of these processes, and shows that while legal integration can benefit certain wealthier categories of people, who fit into the model of an 'entrepreneurial small-scale miner', for others adverse incorporation contributes to socio-economic dependence, exploitation and insecurity. For the issue of marginality to be addressed within integration processes, the existence of local forms of organization, institutions and relationships, which underpin inequalities and discrimination, need to be recognized.

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Multiple subclonal populations of tumor cells can coexist within the same tumor. This intra-tumor heterogeneity will have clinical implications and it is therefore important to identify factors that drive or suppress such heterogeneous tumor progression. Evolutionary biology can provide important insights into this process. In particular, experimental evolution studies of microbial populations, which exist as clonal populations that can diversify into multiple subclones, have revealed important evolutionary processes driving heterogeneity within a population. There are transferrable lessons that can be learnt from these studies that will help us to understand the process of intra-tumor heterogeneity in the clinical setting. In this review, we summarize drivers of microbial diversity that have been identified, such as mutation rate and environmental influences, and discuss how knowledge gained from microbial experimental evolution studies may guide us to identify and understand important selective factors that promote intra-tumor heterogeneity. Furthermore, we discuss how these factors could be used to direct and optimize research efforts to improve patient care, focusing on therapeutic resistance. Finally, we emphasize the need for longitudinal studies to address the impact of these potential tumor heterogeneity-promoting factors on drug resistance, metastatic potential and clinical outcome.

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BACKGROUND: Brain inflammation has been recognized as a complex phenomenon with numerous related aspects. In addition to the very well-described neurodegenerative effect of inflammation, several studies suggest that inflammatory signals exert a potentially positive influence on neural stem cell proliferation, migration and differentiation. Tumor necrosis factor alpha (TNF-alpha) is one of the best-characterized mediators of inflammation. To date, conclusions about the action of TNF on neural stem or progenitor cells (NSCs, NPCs) have been conflicting. TNF seems to activate NSC proliferation and to inhibit their differentiation into NPCs. The purpose of the present study was to analyze the molecular signal transduction mechanisms induced by TNF and resulting in NSC proliferation. RESULTS: Here we describe for the first time the TNF-mediated signal transduction cascade in neural stem cells (NSCs) that results in increased proliferation. Moreover, we demonstrate IKK-alpha/beta-dependent proliferation and markedly up-regulated cyclin D1 expression after TNF treatment. The significant increase in proliferation in TNF-treated cells was indicated by increased neurosphere volume, increased bromodeoxyuridin (BrdU) incorporation and a higher total cell number. Furthermore, TNF strongly activated nuclear factor-kappa B (NF-kappaB) as measured by reporter gene assays and by an activity-specific antibody. Proliferation of control and TNF-treated NSCs was strongly inhibited by expression of the NF-kappaB super-repressor IkappaB-AA1. Pharmacological blockade of IkappaB ubiquitin ligase activity led to comparable decreases in NF-kappaB activity and proliferation. In addition, IKK-beta gene product knock-down via siRNA led to diminished NF-kappaB activity, attenuated cyclin D1 expression and finally decreased proliferation. In contrast, TGFbeta-activated kinase 1 (TAK-1) is partially dispensable for TNF-mediated and endogenous proliferation. Understanding stem cell proliferation is crucial for future regenerative and anti-tumor medicine. CONCLUSION: TNF-mediated activation of IKK-beta resulted in activation of NF-kappaB and was followed by up-regulation of the bona-fide target gene cyclin D1. Activation of the canonical NF-kappaB pathway resulted in strongly increased proliferation of NSCs.

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Many species are extending their leading-edge (cool) range margins polewards in response to recent climate change. In the present study, we investigated range margin changes at the northern (cool) range margins of 1573 southerly-distributed species from 21 animal groups in Great Britain over the past four decades of climate change, updating previous work. Depending on data availability, range margin changes were examined over two time intervals during the past four decades. For four groups (birds, butterflies, macromoths, and dragonflies and damselflies), there were sufficient data available to examine range margin changes over both time intervals. We found that most taxa shifted their northern range margins polewards and this finding was not greatly influenced by changes in recorder effort. The mean northwards range margin change in the first time interval was 23 km per decade (N = 13 taxonomic groups) and, in the second interval, was 18 km per decade (N = 16 taxonomic groups) during periods when the British climate warmed by 0.21 and 0.28 °C per decade, respectively. For the four taxa examined over both intervals, there was evidence for higher rate of range margin change in the more recent time interval in the two Lepidoptera groups. Our analyses confirm a continued range margin shift polewards in a wide range of taxonomic groups.