Free trade and empire in the Anglo-Irish commercial propositions of 1785

William Pitt’s 1785 proposal for a free trade area between Britain and Ireland attempted to use free trade as a mechanism of imperial integration. It was a response to the agitation for political reform in Ireland and followed the attainment of legislative independence in 1782. The proposal aimed at co-ordinating economic and fiscal policy between the kingdoms without imposing explicit political controls. This article establishes that the measure failed because of the lack of consensus around the idea of free trade. Three contrasting ideas of free trade became apparent in the debates around the propositions of 1785: imperial or neo-Mercantilist free trade, Smithean free trade, and national or neo-Machiavellian free trade. Imperial free trade was critical of monopolies but sought to organise trade to the benefit of the imperial metropole; Smithean free trade saw open markets as a discipline that assured efficiency but required imperial institutional frameworks, legally secured, to function. Neo-Machiavellian free trade asserted the right of every political community to organise its trade according to its interests. The article establishes the genealogy of these three positions in pamphlet debates and political correspondence in Britain and Ireland from 1689 to 1785. It argues that majority political opinion in Ireland, with exceptions, understood free trade in a neo-Machiavellian sense while Pitt was committed to a Smithean ideal. The propositions collapsed because these internal tensions became more evident under the pressure of criticism. Liberal political economy did not of itself offer a route to a British exceptionality that finessed the tensions inherent in empire

Les réseaux de crédit en Languedoc au xviiie siècle et les origines sociales de la révolution

Alors que l’historiographie prête une attention croissante aux processus par les quels les nouvelles institutions sociales conduisent à la Révolution, l’application des interrogations déjà soulevées à propos de la famille ou de la consommation, au problème du crédit semble logique. Le Languedoc offre à cet égard un terrain intéressant en raison de ses institutions provinciales, de son système fiscal et des caractéristiques de ses élites. Effectivement, l’extension et le contrôle des pratiques du crédit, notamment en rapport avec les exigences financières de l’État monarchique et l’alourdissement de sa dette, sont des enjeux cruciaux autour desquels se nouent les tensions préliminaires à la Révolution. Parmi les enjeux figurent notamment la poursuite des investissements dans les équipements du développement économique de la région et la répartition des ressources entre les multiples acteurs sociaux, paysans et autres notamment. Cette contribution invite à des études sur la participation populaire à la transformation des institutions sociales et sur les figures régionales de ces transformations à la fi n du xviiie siècle.While the historiography has had its “Durkheimien Moment” in examining the process by which new social institutions led to the Revolution, questions already raised about the family or consumption, can be reasonably applied to the problem of credit. Languedoc is in this respect an interesting region given its provincial institutions, its fiscal system, and the characteristics of its elites. Indeed, the extension and control of the practices of credit, notably those related to the financial demands of the monarchical State and its increasing debt, are the crucial issues a round which the preliminary tensions of the Revolution developed. Prominent among the issues were the pursuit of investment in the equipment of the economic development of the region and the distribution of resources between multiple social groups, especially peasants. This article encourages further studies on the popular participation in the transformation of social institutions and on the regional personalities involved in these transformations at the end of the eighteenth century

Étienne Clavière, Jacques-Pierre Brissot et les fondations intellectuelles de la politique des girondins

Le but de cet article est de permettre une compréhension plus précise des origines de l’idéologie girondine à partir d’une analyse des écrits de deux personnages qui furent les premiers à formuler les idées politiques définissant celle-ci dans les années 1790  : Jacques-Pierre Brissot et Étienne Clavière. Cet article veut montrer que les idées girondines ne peuvent être comprises qu’avec en toile de fond la révolution de Genève de 1782, tandis que l’essai ultérieur de faire de la France une république moderne, plutôt qu’une monarchie civilisée défendue par Turgot ou une république radicale jacobine, ne peut être étudié qu’à la lumière de l’échec de cette révolution.Étienne Clavière, Jacques-Pierre Brissot and the intellectual origins of Girondin politics.The aim of this paper is a more precise understanding of the origins of Girondin ideology. Since it is not possible to provide an analysis of the writings of all of the members of the group attention focuses on two figures who were the first to formulate the political ideas that defined a Girondin in the early 1790s. The first is Jacques-Pierre Brissot and the second Étienne Clavière. The central claim of this paper is that Girondin ideas can only be understood against the background of the Genevan revolution of 1782 and the subsequent attempt, in the light of the failure of the Genevan revolution, to make France into a modern republic rather than a Jacobin classical republic or a civilized monarchy of the kind advocated by Turgot

Developing a National Design Scoreboard

Recognising the growing importance of design, this paper reports on the development of an approach to measuring design at a national level. A series of measures is proposed, that are based around a simplified model of design as a system at a national level. This model was developed though insights from literature and a workshop with government, industry and design sector representatives. Detailed data on design in the UK is presented to highlight the difficulties in collecting reliable and robust data. Evidence is compared with four countries (Spain, Canada, Korea and Sweden). This comparison highlights the inherent difficulties in comparing performance and a revised set of measures is proposed. Finally, an approach to capturing design spend at a firm level is proposed, based on insights from literature and case studies. Keywords: National Design System, Design Performance</p

Reversible Block of Mouse Neural Stem Cell Differentiation in the Absence of Dicer and MicroRNAs

BACKGROUND: To investigate the functions of Dicer and microRNAs in neural stem (NS) cell self-renewal and neurogenesis, we established neural stem cell lines from the embryonic mouse Dicer-null cerebral cortex, producing neural stem cell lines that lacked all microRNAs. PRINCIPAL FINDINGS: Dicer-null NS cells underwent normal self-renewal and could be maintained in vitro indefinitely, but had subtly altered cell cycle kinetics and abnormal heterochromatin organisation. In the absence of all microRNAs, Dicer-null NS cells were incapable of generating either glial or neuronal progeny and exhibited a marked dependency on exogenous EGF for survival. Dicer-null NS cells assumed complex differences in mRNA and protein expression under self-renewing conditions, upregulating transcripts indicative of self-renewing NS cells and expressing genes characteristic of differentiating neurons and glia. Underlining the growth-factor dependency of Dicer-null NS cells, many regulators of apoptosis were enriched in expression in these cells. Dicer-null NS cells initiate some of the same gene expression changes as wild-type cells under astrocyte differentiating conditions, but also show aberrant expression of large sets of genes and ultimately fail to complete the differentiation programme. Acute replacement of Dicer restored their ability to differentiate to both neurons and glia. CONCLUSIONS: The block in differentiation due to loss of Dicer and microRNAs is reversible and the significantly altered phenotype of Dicer-null NS cells does not constitute a permanent transformation. We conclude that Dicer and microRNAs function in this system to maintain the neural stem cell phenotype and to facilitate the completion of differentiation

MLS Measurements of Stratospheric Hydrogen Cyanide During the 2015-2016 El Niño Event

It is known from ground-based measurements made during the 1982-1983 and 1997-1998 El Niño events that atmospheric hydrogen cyanide (HCN) tends to be higher during such years than at other times. The Microwave Limb Sounder (MLS) on the Aura satellite has been measuring HCN mixing ratios since launch in 2004; the measurements are ongoing at the time of writing. The winter of 2015- 2016 saw the largest El Niño event since 1997-1998. We present MLS measurements of HCN in the lower stratosphere for the Aura mission to date, comparing the 2015- 2016 El Niño period to the rest of the mission. HCN in 2015- 2016 is higher than at any other time during the mission, but ground-based measurements suggest that it may have been even more elevated in 1997-1998. As the MLS HCN data are essentially unvalidated, we show them alongside data from the MIPAS and ACE-FTS instruments; the three instruments agree reasonably well in the tropical lower stratosphere. Global HCN emissions calculated from the Global Fire Emissions Database (GFED v4.1) database are much greater during large El Niño events and are greater in 1997- 1998 than in 2015-2016, thereby showing good qualitative agreement with the measurements. Correlation between El Niño-Southern Oscillation (ENSO) indices, measured HCN, and GFED HCN emissions is less clear if the 2015-2016 event is excluded. In particular, the 2009-2010 winter had fairly strong El Niño conditions and fairly large GFED HCN emissions, but very little effect is observed in the MLS HCN

PMC42, a breast progenitor cancer cell line, has normal-like mRNA and microRNA transcriptomes.

INTRODUCTION: The use of cultured cell lines as model systems for normal tissue is limited by the molecular alterations accompanying the immortalisation process, including changes in the mRNA and microRNA (miRNA) repertoire. Therefore, identification of cell lines with normal-like expression profiles is of paramount importance in studies of normal gene regulation. METHODS: The mRNA and miRNA expression profiles of several breast cell lines of cancerous or normal origin were measured using printed slide arrays, Luminex bead arrays, and real-time reverse transcription-polymerase chain reaction. RESULTS: We demonstrate that the mRNA expression profiles of two breast cell lines are similar to that of normal breast tissue: HB4a, immortalised normal breast epithelium, and PMC42, a breast cancer cell line that retains progenitor pluripotency allowing in-culture differentiation to both secretory and myoepithelial fates. In contrast, only PMC42 exhibits a normal-like miRNA expression profile. We identified a group of miRNAs that are highly expressed in normal breast tissue and PMC42 but are lost in all other cancerous and normal-origin breast cell lines and observed a similar loss in immortalised lymphoblastoid cell lines compared with healthy uncultured B cells. Moreover, like tumour suppressor genes, these miRNAs are lost in a variety of tumours. We show that the mechanism leading to the loss of these miRNAs in breast cancer cell lines has genomic, transcriptional, and post-transcriptional components. CONCLUSION: We propose that, despite its neoplastic origin, PMC42 is an excellent molecular model for normal breast epithelium, providing a unique tool to study breast differentiation and the function of key miRNAs that are typically lost in cancer.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are