557 research outputs found

    Girls’ and women’s education within Unesco and the World Bank, 1945–2000

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    By 2000, girls’ and women’s education was a priority for international development organisations. While studies have examined the impact of recent campaigns and programmes, there has been less exploration of ideas about girls’ and women’s education within development thought in the immediate post?colonial period, and the political mechanisms through which this came to be a global concern. Through a study of policy documents, this paper investigates how the education of girls and women came to be prioritised within the two principle UN agencies involved with education since 1945, the World Bank and Unesco. A shift in priorities is evident, from ensuring formal rights and improving the status of women, to expanding the productive capacities of women, fertility control and poverty reduction. While the ascendance of human capital theory provided a space for a new perception of the role of women’s education in development, in other policy arenas women’s education was central to exploring more substantive, rights?based notions of gender equality. Ultimately, the goal of improving girls’ and women’s education fitted into diverse development agendas, paving the way for it to become a global development priority

    Application of molecular dynamics techniques and luminescent probes to the study of glass structure: the SiO2–GeO2 case

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    In this paper, we report on the results obtained from molecular dynamic simulation of a Eu3+-doped germanosilicate glass. This simulation provides further information on the structure. In particular it reveals a homogeneous distribution of SiO4 and GeO4 units, a decrease of defects compared to SiO2 and GeO2 glasses, and a trend to clustering of the doping ions. Using the modified crystal-field theory, the luminescence spectroscopic properties have been computed and comparison with experimental data has allowed a correlation of the spectral features with two main types of local environment depending on the coordination number and on the medium-range arrangement around the doping ions

    Declining partisan representation at the sub-national level: assessing and explaining the strengthening of local lists in Italian municipalities (1995–2014)

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    In Western democracies political representation at the national level is still dominated by (old and new) political parties. This article shows that, instead, the representative role of parties may have declined at the local level. In Italy, for instance, the average share of municipal seats held by non-partisan councillors has almost tripled in the last 20 years. By using an original data set, this article classifies different types of Italian local lists, assesses their relationship with traditional parties and explains territorial variation in their success. The results suggest that local lists have become substantially stronger in small municipalities, in regions characterised by weak or declining political subcultures and where regionalist parties are absent or irrelevant. Finally, contrary to the expectation that declining partisanship is linked to modernisation processes and direct civic engagement, local lists have achieved their best results in the less developed areas of the country

    Group Incentives and Rational Voting

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    Our model describes competition between groups driven by the choices of self-interested voters within groups. Within a Poisson voting environment, parties observe aggregate support from groups and can allocate prizes or punishments to them. In a tournament style analysis, the model characterizes how contingent allocation of prizes based on relative levels of support affects equilibrium voting behavior. In addition to standard notions of pivotality, voters influence the distribution of prizes across groups. Such prize pivotality supports positive voter turnout even in non-competitive electoral settings. The analysis shows that competition for a prize awarded to the most supportive group is only stable when two groups actively support a party. However, competition among groups to avoid punishment is stable in environments with any number of groups. We conclude by examining implications for endogenous group formation and how politicians structure the allocation of rewards and punishments.Comment: 34 pages, 1 figur

    A Genome-Wide Collection of Mos1 Transposon Insertion Mutants for the C. elegans Research Community

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    Methods that use homologous recombination to engineer the genome of C. elegans commonly use strains carrying specific insertions of the heterologous transposon Mos1. A large collection of known Mos1 insertion alleles would therefore be of general interest to the C. elegans research community. We describe here the optimization of a semi-automated methodology for the construction of a substantial collection of Mos1 insertion mutant strains. At peak production, more than 5,000 strains were generated per month. These strains were then subject to molecular analysis, and more than 13,300 Mos1 insertions characterized. In addition to targeting directly more than 4,700 genes, these alleles represent the potential starting point for the engineered deletion of essentially all C. elegans genes and the modification of more than 40% of them. This collection of mutants, generated under the auspices of the European NEMAGENETAG consortium, is publicly available and represents an important research resource

    Opposite regulation of human versus mouse apolipoprotein A-I by fibrates in human apolipoprotein A-I transgenic mice

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    The regulation of liver apolipoprotein (apo) A-I gene expression by fibrates was studied in human apo A-I transgenic mice containing a human genomic DNA fragment driving apo A-I expression in liver. Treatment with fenofibrate (0.5% wt/wt) for 7 d increased plasma human apo A-I levels up to 750% and HDL-cholesterol levels up to 200% with a shift to larger particles. The increase in human apo A-I plasma levels was time and dose dependent and was already evident after 3 d at the highest dose (0.5% wt/wt) of fenofibrate. In contrast, plasma mouse apo A-I concentration was decreased after fenofibrate in nontransgenic mice. The increase in plasma human apo A-I levels after fenofibrate treatment was associated with a 97% increase in hepatic human apo A-I mRNA, whereas mouse apo A-I mRNA levels decreased to 51%. In nontransgenic mice, a similar down-regulation of hepatic apo A-I mRNA levels was observed. Nuclear run-on experiments demonstrated that the increase in human apo A-I and the decrease in mouse apo A-I gene expression after fenofibrate occurred at the transcriptional level. Since part of the effects of fibrates are mediated through the nuclear receptor PPAR (peroxisome proliferator-activated receptor), the expression of the acyl CoA oxidase (ACO) gene was measured as a control of PPAR activation. Both in transgenic and nontransgenic mice, fenofibrate induced ACO mRNA levels up to sixfold. When transgenic mice were treated with gemfibrozil (0.5% wt/wt) plasma human apo A-I and HDL-cholesterol levels increased 32 and 73%, respectively, above control levels. The weaker effect of this compound on human apo A-I and HDL-cholesterol levels correlated with a less pronounced impact on ACO mRNA levels (a threefold increase) suggesting that the level of induction of human apo A-I gene is related to the PPAR activating potency of the fibrate used. Treatment of human primary hepatocytes with fenofibric acid (500 microM) provoked an 83 and 50% increase in apo A-I secretion and mRNA levels, respectively, supporting that a direct action of fibrates on liver human apo A-I production leads to the observed increase in plasma apo A4 and HDL-cholesterol

    Homeostatic Proliferation Fails to Efficiently Reactivate HIV-1 Latently Infected Central Memory CD4+ T Cells

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    Homeostatic proliferation ensures the longevity of central memory T-cells by inducing cell proliferation in the absence of cellular differentiation or activation. This process is governed mainly by IL-7. Central memory T-cells can also be stimulated via engagement of the T-cell receptor, leading to cell proliferation but also activation and differentiation. Using an in vitro model of HIV-1 latency, we have examined in detail the effects of homeostatic proliferation on latently infected central memory T cells. We have also used antigenic stimulation via anti-CD3/anti-CD28 antibodies and established a comparison with a homeostatic proliferation stimulus, to evaluate potential differences in how either treatment affects the dynamics of latent virus populations. First, we show that homeostatic proliferation, as induced by a combination of IL-2 plus IL-7, leads to partial reactivation of latent HIV-1 but is unable to reduce the size of the reservoir in vitro. Second, latently infected cells are able to homeostatically proliferate in the absence of viral reactivation or cell differentiation. These results indicate that IL-2 plus IL-7 may induce a detrimental effect by favoring the maintenance of the latent HIV-1 reservoir. On the other hand, antigenic stimulation efficiently reactivated latent HIV-1 in cultured central memory cells and led to depletion of the latently infected cells via virus-induced cell death

    "Shock and kill" effects of class I-selective histone deacetylase inhibitors in combination with the glutathione synthesis inhibitor buthionine sulfoximine in cell line models for HIV-1 quiescence

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    Latently infected, resting memory CD4+ T cells and macrophages represent a major obstacle to the eradication of HIV-1. For this purpose, "shock and kill" strategies have been proposed (activation of HIV-1 followed by stimuli leading to cell death). Histone deacetylase inhibitors (HDACIs) induce HIV-1 activation from quiescence, yet class/isoform-selective HDACIs are needed to specifically target HIV-1 latency. We tested 32 small molecule HDACIs for their ability to induce HIV-1 activation in the ACH-2 and U1 cell line models. In general, potent activators of HIV-1 replication were found among non-class selective and class I-selective HDACIs. However, class I selectivity did not reduce the toxicity of most of the molecules for uninfected cells, which is a major concern for possible HDACI-based therapies. To overcome this problem, complementary strategies using lower HDACI concentrations have been explored. We added to class I HDACIs the glutathione-synthesis inhibitor buthionine sulfoximine (BSO), in an attempt to create an intracellular environment that would facilitate HIV-1 activation. The basis for this strategy was that HIV-1 replication decreases the intracellular levels of reduced glutathione, creating a pro-oxidant environment which in turn stimulates HIV-1 transcription. We found that BSO increased the ability of class I HDACIs to activate HIV-1. This interaction allowed the use of both types of drugs at concentrations that were non-toxic for uninfected cells, whereas the infected cell cultures succumbed more readily to the drug combination. These effects were associated with BSO-induced recruitment of HDACI-insensitive cells into the responding cell population, as shown in Jurkat cell models for HIV-1 quiescence. The results of the present study may contribute to the future design of class I HDACIs for treating HIV-1. Moreover, the combined effects of class I-selective HDACIs and the glutathione synthesis inhibitor BSO suggest the existence of an Achilles' heel that could be manipulated in order to facilitate the "kill" phase of experimental HIV-1 eradication strategies

    Identification of factors required for meristem function in Arabidopsis using a novel next generation sequencing fast forward genetics approach

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    <p>Abstract</p> <p>Background</p> <p>Phenotype-driven forward genetic experiments are powerful approaches for linking phenotypes to genomic elements but they still involve a laborious positional cloning process. Although sequencing of complete genomes now becomes available, discriminating causal mutations from the enormous amounts of background variation remains a major challenge.</p> <p>Method</p> <p>To improve this, we developed a universal two-step approach, named 'fast forward genetics', which combines traditional bulk segregant techniques with targeted genomic enrichment and next-generation sequencing technology</p> <p>Results</p> <p>As a proof of principle we successfully applied this approach to two Arabidopsis mutants and identified a novel factor required for stem cell activity.</p> <p>Conclusion</p> <p>We demonstrated that the 'fast forward genetics' procedure efficiently identifies a small number of testable candidate mutations. As the approach is independent of genome size, it can be applied to any model system of interest. Furthermore, we show that experiments can be multiplexed and easily scaled for the identification of multiple individual mutants in a single sequencing run.</p
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