15 resultados para James G McDonald

em Aston University Research Archive


Relevância:

80.00% 80.00%

Publicador:

Resumo:

The election on 6 May 2007 of Nicolas Sarkozy as President of the Republic ushered in the promise of a new era in France. Sarkozy’s presidency follows those of the Socialist François Mitterrand (1981-95) and the neo-Gaullist Jacques Chirac (1995-2007), who together occupied France’s highest political office for more than a quarter-century. From the outset, Sarkozy’s presidential campaign was predicated on the need for change in France, for a “rupture” with the past; and his emphatic victory against the Socialist Ségolène Royal gave him a mandate to effect this. The legislative elections of June 2007, by assuring a strong majority in the National Assembly for Sarkozy’s centre-right Union pour un Mouvement Populaire (UMP), left the way clear for implementing the new President’s reform agenda over the next five years. This article examines the political context within which Sarkozy was elected to power, the main proposals of his presidential program, the challenges he faces, and his prospects for bringing real change to France.

Relevância:

80.00% 80.00%

Publicador:

Resumo:

The Front National has for some years been France's third political party and the most notable far-right force in Europe; its leader, Jean-Marie Le Pen, contested the 2002 presidential election run-off with 5.5 million votes. What do Le Pen and the FN represent? What are their historical roots, their values and their policies? Who votes for them and why? And what has been their impact on the political agenda in France? Adopting an essentially chronological approach, the book traces the political lineage of Le Pen and the FN through key figures, movements and events on the French extreme right from the Vichy regime to the present, providing a detailed historical perspective for understanding the FN today. Part I provides a historical study of the extreme right in France since 1940, examining • the Vichy regime, collaboration and ‘collaborationism’, • the aftermath of Liberation and the post-war extreme right, • the Poujadist movement and the politics of populism, • the Algerian War as a catalyst for change, • the ‘Nouvelle Droite’ and the search for doctrinal renewal, • old and new forms of extreme-right ideology and activism. Part II undertakes a comprehensive study of the FN, analysing • the party’s early development and electoral rise, • its evolving programme and strategy, • the factors underlying its popular appeal, • the geography and composition of its electorate, • its exercise of local power and regional influence, • and its defining impact on the national political agenda. The FN, it is argued, represents both the latest manifestation of a long tradition of authoritarian nationalism and a complex new phenomenon within the changing social and political dynamics of contemporary France.

Relevância:

80.00% 80.00%

Publicador:

Resumo:

Military collaboration is one of the least acknowledged aspects of France under the Occupation. Yet from summer 1941 France raised a number of fighting units for Hitler’s armies, each with its distinctive mission and each drawing the Vichy regime deeper into collaboration with Nazi Germany. This article discusses that process and its diverse implications. It shows how the Paris collaborationists used military engagement to pressure the Vichy government into more activist collaboration and explores the divergent perspectives in which this was viewed from Berlin, Paris and Vichy; it considers the mobilising myths, motivations and misapprehensions behind military collaboration; and it identifies some of the anomalies of that collaboration, with its reconceptualising of France and Other, friend and foe, belonging and alienation. Those French ‘patriots’ who fought in German uniform would become effective exiles from a homeland they departed to ‘defend’ only to see it ‘liberated’ by their ‘enemies’. Exposing the divisions and the delusions underlying military collaboration, the article sheds light on conflicting political calculations and shifting allegiances in occupied France.

Relevância:

80.00% 80.00%

Publicador:

Resumo:

The past two decades have witnessed growing political disaffection and a widening mass/elite disjuncture in France, reflected in opinion polls, rising abstentionism, electoral volatility and fragmentation, with sustained voting against incumbent governments. Though the electoral system has preserved the duopoly of the mainstream coalitions, they have suffered loss of public confidence and swings in electoral support. Stable parliamentary majorities conceal a political landscape of assorted anti-system parties and growing support for far right and far left. The picture is paradoxical: the French express alienation from political parties yet relate positively to their political institutions; they berate national politicians but retain strong bonds with those elected locally; they appear increasingly disengaged from politics yet forms of ‘direct democracy’ are finding new vigour. While the electoral, attitudinal and systemic factors reviewed here may not signal a crisis of democracy, they point to serious problems of political representation in contemporary France.

Relevância:

80.00% 80.00%

Publicador:

Resumo:

Few names resonate more loudly from the French Fourth Republic than that of Pierre Poujade, and few terms exude such a sulfurous odour as le poujadisme. Between 1953 and 1958, the Poujadists secured their place in modern French history, winning 52 seats in the National Assembly and inscribing a lasting entry in the lexicon of political protest. Taking as its starting point the fiftieth anniversary of Poujade’s movement held in its birthplace of Saint-Céré in July 2003, this article reassesses Poujadism fifty years on from its heyday. It considers Poujadism as the first important anti-globalisation movement in post-war France, a locus for the conflict between ‘stalemate’ traditionalism and socio-economic modernisation. It examines the trajectory of the Poujadists from anti-tax movement to political party, arguing the difficulty of defining Poujadism in classic political terms. In particular, the article takes issue with the perception of Poujadism as an extreme-right ideology and interprets it instead as a form of populist protest lacking a solid doctrinal core and opportunistic in its exploitation of political issues and allies. As such, it is argued, Poujadism represents a complex synthesis of both right-wing and left-wing values and discourses, as impervious to definition today as it was fifty years ago. The article considers the brief alliance of convenience between Poujade and Le Pen, and locates in Le Pen’s early Poujadist experience some of the methods and even some of the arguments used by the FN today. It concludes by discussing Poujade’s political activities after 1958, tracing his long-term conversion from violent opposition to the State under the Fourth Republic to co-operation under the Fifth. The author draws here on correspondence with Pierre Poujade up until his death in August 2003.

Relevância:

80.00% 80.00%

Publicador:

Resumo:

Stanley Hoffmann is one of the most eminent political scholars of our age—a renowned authority in the study of French, European, and world politics over half a century, an influential theorist of international relations, a critical analyst of US foreign policy, and a voice of moral conscience in many public debates of his time. Hoffmann has always asked big questions—and to those questions he brings an encyclopedic mind that crosses boundaries between politics, history, sociology, law, philosophy, ethics, and literature. This brief article highlights some aspects of his life and work, and introduces a symposium in his honor bringing together five leading scholars on France, Europe, international relations, and international law—each with an enduring debt to the teaching, writings and example of Stanley Hoffmann.

Relevância:

80.00% 80.00%

Publicador:

Resumo:

The presidential and legislative elections of 2007 are widely seen to have marked the end of the far right as a major political force in France. How could this occur only five years after Le Pen’s qualification for the presidential run-off, and with his party seemingly in the ascendant? This article discusses recent fluctuations in far-right electoral performance in France. It focuses largely on the presidential elections of 2002 and 2007, re-examining the (supposed) upswell of far-right support in 2002 and its (supposed) subsidence in 2007. Both elections require nuanced interpretation. Both confounded poll predictions, which in 2007 failed to measure the effect of Sarkozy’s hard-right campaign and, crucially, the extent to which the border between “mainstream right” and “far right” had shifted since 2002. This allowed Sarkozy to drain part of Le Pen’s electorate, and raises questions over the longer-term impact of Le Pen and the FN on the political agenda in France.

Relevância:

80.00% 80.00%

Publicador:

Resumo:

There is a comforting consensus among political commentators that the 2007 presidential election marked the end of Jean-Marie Le Pen as a force in French politics. The shock election of the Front National leader to the presidential run-off in 2002, by contrast, is explained as a surge in the Le Pen vote specific to the prevailing electoral conditions. This article challenges that interpretation of both elections. It shows that, despite Le Pen’s unforeseen success in 2002, there was no surge of support for him, and that despite Le Pen’s supposed collapse in 2007, he won close to 4 million votes while popular agreement with his ideas rose to its highest recorded level. The article concludes that Le Pen remains a powerful presence in French politics and that his supporters continue to constitute a large and highly influential constituency.

Relevância:

80.00% 80.00%

Publicador:

Resumo:

The surface epithelial cells of the stomach represent a major component of the gastric barrier. A cell culture model of the gastric epithelial cell surface would prove useful for biopharmaceutical screening of new chemical entities and dosage forms. Primary cultures of guinea pig gastric mucous epithelial cells were grown on filter inserts (Transwells®) for 3 days. Tight-junction formation, assessed by transepithelial electrical resistance (TEER) and permeability of mannitol and fluorescein, was enhanced when collagen IV rather than collagen I was used to coat the polycarbonate filter. TEER for cells grown on collagen IV was close to that obtained with intact guinea pig gastric epithelium in vitro. Differentiation was assessed by incorporation of [ 3H]glucosamine into glycoprotein and by activity of NADPH oxidase, which produces superoxide. Both of these measures were greater for cells grown on filters coated with collagen I than for cells grown on plastic culture plates, but no major difference was found between cells grown on collagens I and IV. The proportion of cells, which stained positively for mucin with periodic acid Schiff reagent, was greater than 95% for all culture conditions. Monolayers grown on membranes coated with collagen IV exhibited apically polarized secretion of mucin and superoxide, and were resistant to acidification of the apical medium to pH 3.0 for 30 min. A screen of nonsteroidal anti-inflammatory drugs revealed a novel effect of diclofenac and niflumic acid in reversibly reducing permeability by the paracellular route. In conclusion, the mucous cell preparation grown on collagen IV represents a good model of the gastric surface epithelium suitable for screening procedures. © 2005 The Society for Biomolecular Screening.

Relevância:

80.00% 80.00%

Publicador:

Resumo:

The 'ion-trapping' hypothesis suggests that the intracellular concentration of acidic non-steroidal anti-inflammatory drugs in gastric epithelial cells could be much higher than in the gastric lumen, and that such accumulation could contribute to their gastrotoxicity. Our aim was to examine the effect of the pH of the apical medium on the apical to basal transfer of the acidic drug indomethacin (pK a 4.5) across a gastric mucous epithelial cell monolayer, and to determine whether indomethacin accumulated in cells exposed to a low apical pH. Guinea-pig gastric mucous epithelial cells were grown on porous membrane culture inserts (Transwells®) for 72 h. Transfer and accumulation of [ 14C] indomethacin were assessed by scintillation counting. Transfer of [ 3H]mannitol and measurement of trans-epithelial electrical resistance were used to assess integrity of the monolayer. Distribution of [ 14C] urea was used to estimate the intracellular volume of the monolayer. The monolayer was not disrupted by exposure of the apical face to media of pH ≥ 3, or by indomethacin. Transfer of indomethacin (12 μM) to the basal medium increased with decreasing apical medium pH. The apparent permeability of the undissociated acid was estimated to be five times that of the anion. The intracellular concentration of indomethacin was respectively 5.3, 4.1 and 4.3 times that in the apical medium at pH 5.5, 4.5 and 3.0. In conclusion, this study represents the first direct demonstration that indomethacin accumulates in gastric epithelial cells exposed to low apical pH. However, accumulation of indomethacin was moderate and the predictions of the ion-trapping hypothesis were not met, probably due to the substantial permeability of anionic indomethacin across membranes. © 2006 Elsevier B.V. All rights reserved.

Relevância:

80.00% 80.00%

Publicador:

Resumo:

As optical coherence tomography (OCT) becomes widespread, validation and characterization of systems becomes important. Reference standards are required to qualitatively and quantitatively measure the performance between difference systems. This would allow the performance degradation of the system over time to be monitored. In this report, the properties of the femtosecond inscribed structures from three different systems for making suitable OCT characterization artefacts (phantoms) are analyzed. The parameter test samples are directly inscribed inside transparent materials. The structures are characterized using an optical microscope and a swept-source OCT. The high reproducibility of the inscribed structures shows high potential for producing multi-modality OCT calibration and characterization phantoms. Such that a single artefact can be used to characterize multiple performance parameters such the resolution, linearity, distortion, and imaging depths. © 2012 SPIE.

Relevância:

80.00% 80.00%

Publicador:

Relevância:

30.00% 30.00%

Publicador:

Resumo:

Orexins A and B (ORA and ORB) are neuropeptide hormones found throughout the central nervous system and periphery. They are required for a host of physiological processes including mitogen-activated protein kinase (MAPK) regulation, steroidogenesis, appetite control and energy regulation. While some signalling mechanisms have been proposed for individual recombinant orexin receptors in generic mammalian cell types, it is clear that the peripheral effects of orexin are spatially and temporally complex. This study dissects the different G-protein signalling and MAPK pathways activated in a pluripotent human adrenal H295R cell line capable of all the physiological steps involved in steroidogenesis. Both extracellular receptor kinase 1/2 (ERK1/2) and p38 were phosphorylated rapidly with a subsequent decline, in a time- and dose-dependent manner, in response to both ORA and ORB. Conversely, there was little or no direct activation of the ERK5 or JNK pathway. Analysis using signalling and MAPK inhibitors as well as receptor-specific antagonists determined the precise mediators of the orexin response in these cells. Both ERK1/2 and p38 activation were predominantly Gq- and to a lesser extent Gs-mediated; p38 activation even had a small Gi-component. Effects were broadly comparable for both orexin sub-types ORA and ORB and although most of the effects were transmitted through the orexin receptor-1 subtype, we did observe a role for orexin receptor-2-mediated activation of both ERK1/2 and p38. Cortisol secretion also differed in response to ORA and ORB. These data suggest multiple roles for orexin-mediated MAPK activation in an adrenal cell-line, this complexity may help to explain the diverse biological actions of orexins with wide-ranging consequences for our understanding of the mechanisms initiated by these steroidogenic molecules.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

Modelling class B G-protein-coupled receptors (GPCRs) using class A GPCR structural templates is difficult due to lack of homology. The plant GPCR, GCR1, has homology to both class A and class B GPCRs. We have used this to generate a class A-class B alignment, and by incorporating maximum lagged correlation of entropy and hydrophobicity into a consensus score, we have been able to align receptor transmembrane regions. We have applied this analysis to generate active and inactive homology models of the class B calcitonin gene-related peptide (CGRP) receptor, and have supported it with site-directed mutagenesis data using 122 CGRP receptor residues and 144 published mutagenesis results on other class B GPCRs. The variation of sequence variability with structure, the analysis of polarity violations, the alignment of group-conserved residues and the mutagenesis results at 27 key positions were particularly informative in distinguishing between the proposed and plausible alternative alignments. Furthermore, we have been able to associate the key molecular features of the class B GPCR signalling machinery with their class A counterparts for the first time. These include the [K/R]KLH motif in intracellular loop 1, [I/L]xxxL and KxxK at the intracellular end of TM5 and TM6, the NPXXY/VAVLY motif on TM7 and small group-conserved residues in TM1, TM2, TM3 and TM7. The equivalent of the class A DRY motif is proposed to involve Arg(2.39), His(2.43) and Glu(3.46), which makes a polar lock with T(6.37). These alignments and models provide useful tools for understanding class B GPCR function.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

Association of receptor activity-modifying proteins (RAMP1-3) with the G protein-coupled receptor (GPCR) calcitonin receptor-like receptor (CLR) enables selective recognition of the peptides calcitonin gene-related peptide (CGRP) and adrenomedullin (AM) that have diverse functions in the cardiovascular and lymphatic systems. How peptides selectively bind GPCR:RAMP complexes is unknown. We report crystal structures of CGRP analog-bound CLR:RAMP1 and AM-bound CLR:RAMP2 extracellular domain heterodimers at 2.5 and 1.8 Å resolutions, respectively. The peptides similarly occupy a shared binding site on CLR with conformations characterized by a β-turn structure near their C termini rather than the α-helical structure common to peptides that bind related GPCRs. The RAMPs augment the binding site with distinct contacts to the variable C-terminal peptide residues and elicit subtly different CLR conformations. The structures and accompanying pharmacology data reveal how a class of accessory membrane proteins modulate ligand binding of a GPCR and may inform drug development targeting CLR:RAMP complexes.