Geopolitics, Global Governance and Crisis Narratives

The financial crisis demonstrated a new quality of interconnected vulnerabilities across the globe. Yet, increased interdependence may lead to increased friction rather than common problem?solving or a shared outlook. This article is concerned with the prospects for future reform of global economic governance, taking as a starting point the apparent shift from the G8 to the G20 as the focal forum for reform. We show that (1) the crisis both reflects and propels important geopolitical change and that (2) interpretations of the crisis differ widely, leading to diverging ideas of different actors about each other and about future reforms. We then consider some implications, notably with regard to the utility of summit?level diplomacy and the transfer of responsibilities to controversial institutions, all within an environment marked by ongoing uncertainty

Helical Chirality: a Link between Local Interactions and Global Topology in DNA

DNA supercoiling plays a major role in many cellular functions. The global DNA conformation is however intimately linked to local DNA-DNA interactions influencing both the physical properties and the biological functions of the supercoiled molecule. Juxtaposition of DNA double helices in ubiquitous crossover arrangements participates in multiple functions such as recombination, gene regulation and DNA packaging. However, little is currently known about how the structure and stability of direct DNA-DNA interactions influence the topological state of DNA. Here, a crystallographic analysis shows that due to the intrinsic helical chirality of DNA, crossovers of opposite handedness exhibit markedly different geometries. While right-handed crossovers are self-fitted by sequence-specific groove-backbone interaction and bridging Mg2+ sites, left-handed crossovers are juxtaposed by groove-groove interaction. Our previous calculations have shown that the different geometries result in differential stabilisation in solution, in the presence of divalent cations. The present study reveals that the various topological states of the cell are associated with different inter-segmental interactions. While the unstable left-handed crossovers are exclusively formed in negatively supercoiled DNA, stable right-handed crossovers constitute the local signature of an unusual topological state in the cell, such as the positively supercoiled or relaxed DNA. These findings not only provide a simple mechanism for locally sensing the DNA topology but also lead to the prediction that, due to their different tertiary intra-molecular interactions, supercoiled molecules of opposite signs must display markedly different physical properties. Sticky inter-segmental interactions in positively supercoiled or relaxed DNA are expected to greatly slow down the slithering dynamics of DNA. We therefore suggest that the intrinsic helical chirality of DNA may have oriented the early evolutionary choices for DNA topology

Molecular Prognostic Prediction for Locally Advanced Nasopharyngeal Carcinoma by Support Vector Machine Integrated Approach

BACKGROUND:Accurate prognostication of locally advanced nasopharyngeal carcinoma (NPC) will benefit patients for tailored therapy. Here, we addressed this issue by developing a mathematical algorithm based on support vector machine (SVM) through integrating the expression levels of multi-biomarkers. METHODOLOGY/PRINCIPAL FINDINGS:Ninety-seven locally advanced NPC patients in a randomized controlled trial (RCT), consisting of 48 cases serving as training set and 49 cases as testing set of SVM models, with 5-year follow-up were studied. We designed SVM models by selecting the variables from 38 tissue molecular biomarkers, which represent 6 tumorigenesis signaling pathways, and 3 EBV-related serological biomarkers. We designed 3 SVM models to refine prognosis of NPC with 5-year follow-up. The SVM1 displayed highly predictive sensitivity (sensitivity, specificity were 88.0% and 81.9%, respectively) by integrating the expression of 7 molecular biomarkers. The SVM2 model showed highly predictive specificity (sensitivity, specificity were 84.0% and 94.5%, respectively) by grouping the expression level of 12 molecular biomarkers and 3 EBV-related serological biomarkers. The SVM3 model, constructed by combination SVM1 with SVM2, displayed a high predictive capacity (sensitivity, specificity were 88.0% and 90.3%, respectively). We found that 3 SVM models had strong power in classification of prognosis. Moreover, Cox multivariate regression analysis confirmed these 3 SVM models were all the significant independent prognostic model for overall survival in testing set and overall patients. CONCLUSIONS/SIGNIFICANCE:Our SVM prognostic models designed in the RCT displayed strong power in refining patient prognosis for locally advanced NPC, potentially directing future target therapy against the related signaling pathways

Sensitivity of endorectal ecography in the staging of rectal chancre: correlation with pathological staging

Objectivo: Avaliar a sensibilidade da ecografia endorectal, em nossa experiência, no estadiamento do cancro do recto comparando com o resultado anatomopatológico. Material e métodos: Estudo retrospectivo, realizado entre Janeiro de 2005 e Agosto de 2009. Calculou-se a sensibilidade, a especificidade, o valor preditivo positivo e negativo para cada estadio T e N. Por meio da ela-boração de curvas ROC avaliou-se a precisão do estadiamento ecoendoscópico e por meio do teste de McNemar comparou-se com o resultado anatomopatológico. Resultados: Dos 112 doentes, 76 cumpriram os critérios de inclusão. Obtivemos uma eficácia de 75 a 97% para uT e de 75% para uN. Verificou-se sensibilidade, especificidade, valor preditivo positivo e negativo, respectivamente, de 63;98;92 e 89% para uT1; 71;76;54 e 88% para uT2; 67;81;73 e 76% para uT3; 100;97;60 e 100% para uT4; e 39;91;62 e 78% para uN. As curvas ROC indicaram que a ecografia endorectal é um bom teste para o estadiamento do T e razoável para o N. O teste de Mc-Nemar revelou que não há diferenças significativas entre o estadiamento ecoendoscópico e anatomopatológico (p>0,05). Conclusões: Conclui-se que a ecografia endorectal é uma importante ferramenta no estadiamento do cancro do recto, apresentando boa correlação com o resultado anatomopatológico.(undefined

Introduction to the Special Issue on 'Historical Perspectives on Punishment and Prisons: representations and realities'

In relation to the early American penal experiment, we might imagine an unbroken line of development that takes us from William Penn's code of 1682 through to the monumental structures of the Jacksonian era. These were to be sources of civic pride and would locate the penitentiary as a utopic site (Rothman). However, at each stage of this evolution of imprisonment, there was a Gothic undercurrent. In analysing these early penitentiaries, their architecture and the popular literature relating to them, we can begin to unpack the ongoing construction of the ‘place myth’ of the prison within the penal imagination