Enforced covalent trimerisation of soluble feline CD134 (OX40)-ligand generates a functional antagonist of feline immunodeficiency virus.

The feline immunodeficiency virus (FIV) targets activated CD4-positive helper T cells preferentially, inducing an AIDS-like immunodeficiency in its natural host species, the domestic cat. The primary receptor for FIV is CD134, a member of the tumour necrosis factor receptor superfamily (TNFRSF) and all primary viral strains tested to date use CD134 for infection. To investigate the effect of the natural ligand for CD134 on FIV infection, feline CD134L was cloned and expressed in soluble forms. However, in contrast to murine or human CD134L, soluble feline CD134L (sCD134L) did not bind to CD134. Receptor-binding activity was restored by enforced covalent trimerisation following the introduction of a synthetic trimerisation domain from tenascin (TNC). Feline and human TNC-CD134Ls retained the species-specificity of the membrane-bound forms of the ligand while murine TNC-CD134L displayed promiscuous binding to feline, human or murine CD134. Feline and murine TNC-CD134Ls were antagonists of FIV infection; however, potency was both strain-specific and substrate-dependent, indicating that the modulatory effects of endogenous sCD134L, or exogenous CD134Lbased therapeutics, may vary depending on the viral strain.

After Satan : Essays in Honour of Neil Forsyth

This volume is the result of a collective desire to pay homage to Neil Forsyth, whose work has significantly contributed to scholarship on Satan. This volume is "after" Satan in more ways than one, tracing the afterlife of both the satanic figure in literature and of Neil Forsyth's contribution to the field, particularly in his major books The Old Enemy: Satan and the Combat Myth (Princeton University Press, 1987, revised 1990) and The Satanic Epic (Princeton University Press, 2003). The essays in this volume draw on Forsyth's work as a focus for their analyses of literary encounters with evil or with the Devil himself, reflecting the richness and variety of contemporary approaches to the age-old question of how to represent evil. All the contributors acknowledge Neil Forsyth's influence in the study of both the Satan-figure and Milton's Paradise Lost. But beyond simply paying homage to Neil Forsyth, the articles collected here trace the lineage of the Satan figure through literary history, showing how evil can function as a necessary other against which a community may define itself. They chart the demonised other through biblical history and medieval chronicle, Shakespeare and Milton, to nineteenth-century fiction and the contemporary novel. Many of the contributors find that literary evil is mediated through the lens of the Satan of Paradise Lost, and their articles address the notion, raised by Neil Forsyth in The Satanic Epic, that the literary Devil-figures under consideration are particularly interested in linguistic ambivalence and the twisted texture of literary works themselves. The multiple responses to evil and the continuous reinvention of the devil figure through the centuries all reaffirm the textual presence of the Devil, his changing forms necessarily inscribed in the shifting history of western literary culture. These essays are a tribute to the work of Neil Forsyth, whose scholarship has illuminated and guided the study of the Devil in English and other literatures.

Devenir parent : divergences et convergences interindividuelles dans une transition de vie

RésuméLa naissance du premier enfant est un événement normatif à l'origine de nombreux changements dans le parcours de vie des hommes et des femmes. La présente recherche s'intéresse à la transition à la parentalité en tant que moment à l'origine d'un processus de stratification sociale. Trois dimensions dépendantes sont étudiées du point de vue de leur changement: l'insertion professionnelle, le travail domestique et la qualité de la relation conjugale. Les concepts de divergence et de convergence interindividuelle, élaborés à partir de l'hypothèse des dés/avantages cumulatifs et de l'hypothèse alternative des effets compensatoires, sont utilisés pour opérationnaliser le changement qui se produit dans ces trois dimensions lors de la naissance du premier enfant.Les résultats montrent, dans un premier moment, la présence de divergences entre les hommes et les femmes dans chacune de ces trois dimensions. Ces divergences inter-sexe sont associées à des convergences entre les individus de même sexe. Les analyses se focalisent dans un deuxième moment, sur les divergences et convergences ultérieures qui se produisent entre individus du même sexe en fonction des ressources sociales, culturelles et économiques initiales. Quelles sont ainsi, par exemple, les mères qui ne diminuent pas leur taux d'occupation initial? Quels sont les pères qui réduisent moins que les autres leur investissement dans le travail domestique? Quels sont les parents qui connaissent une moindre diminution de la qualité de leur relation conjugale? Les réponses données à ces questions montrent comment le processus de stratification sociale au sein d'une cohorte doit être expliqué en relation avec le changement qui se produit lors d'une transition spécifique et non seulement en tant que résultat du simple passage du temps.AbstractThe birth of the first child is a normative event creating important changes in the life course of men and women. This research analyzes the transition to parenthood as a moment creating social stratification. Three dependent dimensions are studied in their change: the occupational career, the domestic labour and the conjugal relationship's quality. The concepts of interindividual divergences and convergence, conceived from the cumulative dis/advantage hypothesis and the alternative hypothesis of compensatory effects, are used to operationalize the change in these three dimensions after the birth of the first child.Results show that, firstly, divergences take place between men and women becoming parents in the three dependent dimensions. Inter-sex divergences are associated to convergence between same-sex individuals. Secondly, the analyses focus on further di/convergences taking place between same-sex individuals, in relation with the initial social, cultural and economical resources. Who are the mothers who will not reduce their initial occupational rates? Who are the fathers who will reduce less than the others their involvement in the domestic tasks? Who are the parents who will experience a less important reduction in their conjugal relationship's quality? The answers to these questions show how the process of social stratification within a cohort has to be explained in relation with the change taking place during a specific transition and not only as a result of the simple passage of time.

Character Networks and Centrality

A character network represents relations between characters from a text; the relations are based on text proximity, shared scenes/events, quoted speech, etc. Our project sketches a theoretical framework for character network analysis, bringing together narratology, both close and distant reading approaches, and social network analysis. It is in line with recent attempts to automatise the extraction of literary social networks (Elson, 2012; Sack, 2013) and other studies stressing the importance of character- systems (Woloch, 2003; Moretti, 2011). The method we use to build the network is direct and simple. First, we extract co-occurrences from a book index, without the need for text analysis. We then describe the narrative roles of the characters, which we deduce from their respective positions in the network, i.e. the discourse. As a case study, we use the autobiographical novel Les Confessions by Jean-Jacques Rousseau. We start by identifying co-occurrences of characters in the book index of our edition (Slatkine, 2012). Subsequently, we compute four types of centrality: degree, closeness, betweenness, eigenvector. We then use these measures to propose a typology of narrative roles for the characters. We show that the two parts of Les Confessions, written years apart, are structured around mirroring central figures that bear similar centrality scores. The first part revolves around the mentor of Rousseau; a figure of openness. The second part centres on a group of schemers, depicting a period of deep paranoia. We also highlight characters with intermediary roles: they provide narrative links between the societies in the life of the author. The method we detail in this complete case study of character network analysis can be applied to any work documented by an index. Un réseau de personnages modélise les relations entre les personnages d'un récit : les relations sont basées sur une forme de proximité dans le texte, l'apparition commune dans des événements, des citations dans des dialogues, etc. Notre travail propose un cadre théorique pour l'analyse des réseaux de personnages, rassemblant narratologie, close et distant reading, et analyse des réseaux sociaux. Ce travail prolonge les tentatives récentes d'automatisation de l'extraction de réseaux sociaux tirés de la littérature (Elson, 2012; Sack, 2013), ainsi que les études portant sur l'importance des systèmes de personnages (Woloch, 2003; Moretti, 2011). La méthode que nous utilisons pour construire le réseau est directe et simple. Nous extrayons les co-occurrences d'un index sans avoir recours à l'analyse textuelle. Nous décrivons les rôles narratifs des personnages en les déduisant de leurs positions relatives dans le réseau, donc du discours. Comme étude de cas, nous avons choisi le roman autobiographique Les Confessions, de Jean- Jacques Rousseau. Nous déduisons les co-occurrences entre personnages de l'index présent dans l'édition Slatkine (Rousseau et al., 2012). Sur le réseau obtenu, nous calculons quatre types de centralité : le degré, la proximité, l'intermédiarité et la centralité par vecteur propre. Nous utilisons ces mesures pour proposer une typologie des rôles narratifs des personnages. Nous montrons que les deux parties des Confessions, écrites à deux époques différentes, sont structurées autour de deux figures centrales, qui obtiennent des mesures de centralité similaires. La première partie est construite autour du mentor de Rousseau, qui a symbolisé une grande ouverture. La seconde partie se focalise sur un groupe de comploteurs, et retrace une période marquée par la paranoïa chez l'auteur. Nous mettons également en évidence des personnages jouant des rôles intermédiaires, et de fait procurant un lien narratif entre les différentes sociétés couvrant la vie de l'auteur. La méthode d'analyse des réseaux de personnages que nous décrivons peut être appliquée à tout texte de fiction comportant un index.

After Satan: Essays in Honour of Neil Forsyth

This volume is the result of a collective desire to pay homage to Neil Forsyth, whose work has significantly contributed to scholarship on Satan. This volume is "after" Satan in more ways than one, tracing the afterlife of both the satanic figure in literature and of Neil Forsyth's contribution to the field, particularly in his major books The Old Enemy: Satan and the Combat Myth (Princeton University Press, 1987, revised 1990) and The Satanic Epic (Princeton University Press, 2003). The essays in this volume draw on Forsyth's work as a focus for their analyses of literary encounters with evil or with the Devil himself, reflecting the richness and variety of contemporary approaches to the age-old question of how to represent evil. All the contributors acknowledge Neil Forsyth's influence in the study of both the Satan-figure and Milton's Paradise Lost. But beyond simply paying homage to Neil Forsyth, the articles collected here trace the lineage of the Satan figure through literary history, showing how evil can function as a necessary other against which a community may define itself. They chart the demonised other through biblical history and medieval chronicle, Shakespeare and Milton, to nineteenth-century fiction and the contemporary novel. Many of the contributors find that literary evil is mediated through the lens of the Satan of Paradise Lost, and their articles address the notion, raised by Neil Forsyth in The Satanic Epic, that the literary Devil-figures under consideration are particularly interested in linguistic ambivalence and the twisted texture of literary works themselves. The multiple responses to evil and the continuous reinvention of the devil figure through the centuries all reaffirm the textual presence of the Devil, his changing forms necessarily inscribed in the shifting history of western literary culture. These essays are a tribute to the work of Neil Forsyth, whose scholarship has illuminated and guided the study of the Devil in English and other literatures.

Prominent use of distal 5' transcription start sites and discovery of a large number of additional exons in ENCODE regions.

This report presents systematic empirical annotation of transcript products from 399 annotated protein-coding loci across the 1% of the human genome targeted by the Encyclopedia of DNA elements (ENCODE) pilot project using a combination of 5' rapid amplification of cDNA ends (RACE) and high-density resolution tiling arrays. We identified previously unannotated and often tissue- or cell-line-specific transcribed fragments (RACEfrags), both 5' distal to the annotated 5' terminus and internal to the annotated gene bounds for the vast majority (81.5%) of the tested genes. Half of the distal RACEfrags span large segments of genomic sequences away from the main portion of the coding transcript and often overlap with the upstream-annotated gene(s). Notably, at least 20% of the resultant novel transcripts have changes in their open reading frames (ORFs), most of them fusing ORFs of adjacent transcripts. A significant fraction of distal RACEfrags show expression levels comparable to those of known exons of the same locus, suggesting that they are not part of very minority splice forms. These results have significant implications concerning (1) our current understanding of the architecture of protein-coding genes; (2) our views on locations of regulatory regions in the genome; and (3) the interpretation of sequence polymorphisms mapping to regions hitherto considered to be "noncoding," ultimately relating to the identification of disease-related sequence alterations.

Political Emotions: Civil Religion and Melodrama in Spielberg's Lincoln

This essay focuses on how Spielberg's film engages with and contributes to the myth of Lincoln as a super-natural figure, a saint more than a hero or great statesman, while anchoring his moral authority in the sentimental rhetoric of the domestic sphere. It is this use of the melodramatic mode, linking the familial space with the national through the trope of the victim-hero, which is the essay's main concern. With Tony Kushner, author of Angels in America, as scriptwriter, it is perhaps not surprising that melodrama is the operative mode in the film. One of the issues that emerge from this analysis is how the film updates melodrama for a contemporary audience in order to minimize what could be perceived as manipulative sentimental devices, observing for most of the film an aesthetic of relative sobriety and realism. In the last hour, and especially the final minutes of the film, melodramatic conventions are deployed in full force and infused with hagiographic iconography to produce a series of emotionally charged moments that create a perfect union of American Civil Religion and classical melodrama. The cornerstone of both cultural paradigms, as deployed in this film, is death: Lincoln's at the hands of an assassin, and the Civil War soldiers', poignantly depicted at key moments of the film. Finally, the essay shows how film melodrama as a genre weaves together the private and the public, the domestic with the national, the familial with the military, and links pathos to politics in a carefully choreographed narrative of sentimentalized mythopoesis.

Monnaie, citoyenneté et globalisation financière. Les citoyens entre protection sociale et promesses de la capitalisation boursière

La monnaie a été étudiée par des économistes hétérodoxes, des sociologues et des historiens qui ont souligné ses rapports à l'ordre collectif, mais elle n'est que rarement analysée sous l'angle de la citoyenneté. Notre thèse propose une réflexion théorique sur quatre types de fonctions (politique, symbolique, socioéconomique et psychoaffective) qui permettent à la monnaie de jouer un rôle de médiation de la citoyenneté. A partir d'une perspective qui combine les apports de l'économie politique internationale et de l'école de la régulation, nous montrons que cette médiation ne mobilise pas seulement des mécanismes sociopolitiques nationaux, mais aussi des mécanismes internationaux qui rétroagissent sur la sphère domestique des États et affectent leur capacité à définir leur régime de citoyenneté. Cette relation est analysée dans le contexte de l'institutionnalisation du système monétaire international de Bretton Woods (1944) et du développement de la globalisation financière depuis les années 1970. Si la monnaie a été mise au service d'un principe de protection des droits sociaux des citoyens contre les pressions financières extérieures après la Seconde guerre mondiale, elle contribue aujourd'hui à l'ouverture de la sphère domestique des Etats aux flux de capitaux transnationaux et à la création d'un ordre politique et juridique favorable aux droits des investisseurs. Cette dynamique est impulsée par l'essor de nouveaux intermédiaires financiers (notamment les agences de notation et les investisseurs institutionnels) et l'émergence concomitante d'une nouvelle forme d'Etat légitimée à partir d'un discours politique néolibéral insistant sur la quête de compétitivité, la réduction de la protection sociale et la responsabilisation individuelle. Elle se traduit par la privatisation des régimes de retraite et le développement des politiques d'éducation financière qui incitent les citoyens à se comporter en « preneurs de risques » actifs et responsables, assurant eux-mêmes leur sécurité économique à travers le placement de leur épargne retraite sur les marchés financiers. Nous soulignons toutefois les difficultés institutionnelles, cognitives et socioéconomiques qui rendent cette transformation de la citoyenneté contradictoire et problématique. Money has been studied by heterodox economists, sociologists and historians who stressed its relationship to collective order. However, it has hardly been analysed from the viewpoint of its relationship to citizenship. We propose a theoretical account of four types of functions (political, symbolic, socioeconomic and psychoaffective) enabling money to operate as a mediation of citizenship. From a perspective that combines the contributions of international political economy and the regulation school, we show that this mediation mobilises not only national sociopolitical mechanisms, but also international mechanisms which feed back on the domestic sphere of states and affect their capacity to define their regime of citizenship. This relationship is analysed in the context of the institutionalisation of the international monetary system of Bretton Woods (1944) and the development of financial globalization since the 1970s. If money has served to protect the social rights of citizens against external financial pressures after the Second World War, today it contributes to the opening of the domestic sphere of states to transnational capital flows and to the creation of a political and legal order favorable to the rights of investors. This dynamic is driven by the rise of new financial intermediaries (in particular rating agencies and institutional investisors) and the simultaneous emergence of a new form of state legitimized from a neoliberal political discourse emphasizing the quest for competitiveness, reduced social protection and individual responsibilization. It results in the privatization of pension systems and the development of policies of financial education that encourage citizens to behave as active and responsible « risk takers », ensuring their own economic security through the investment of their savings retirement on financial markets. However, we emphasize the institutional, cognitive and socioeconomic difficulties that make this transformation of citizenship contradictory and problematic. - Money has been studied by heterodox economists, sociologists and historians who stressed its relationship to collective order. However, it has hardly been analysed from the viewpoint of its relationship to citizenship. We propose a theoretical account of four types of functions (political, symbolic, socioeconomic and psychoaffective) enabling money to operate as a mediation of citizenship. From a perspective that combines the contributions of international political economy and the regulation school, we show that this mediation mobilises not only national sociopolitical mechanisms, but also international mechanisms which feed back on the domestic sphere of states and affect their capacity to define their regime of citizenship. This relationship is analysed in the context of the institutionalisation of the international monetary system of Bretton Woods (1944) and the development of financial globalization since the 1970s. If money has served to protect the social rights of citizens against external financial pressures after the Second World War, today it contributes to the opening of the domestic sphere of states to transnational capital flows and to the creation of a political and legal order favorable to the rights of investors. This dynamic is driven by the rise of new financial intermediaries (in particular rating agencies and institutional investisors) and the simultaneous emergence of a new form of state legitimized from a neoliberal political discourse emphasizing the quest for competitiveness, reduced social protection and individual responsibilization. It results in the privatization of pension systems and the development of policies of financial education that encourage citizens to behave as active and responsible « risk takers », ensuring their own economic security through the investment of their savings retirement on financial markets. However, we emphasize the institutional, cognitive and socioeconomic difficulties that make this transformation of citizenship problematic.

Evolution of Genetic Techniques: Past, Present, and Beyond.

Genetics is the study of heredity, which means the study of genes and factors related to all aspects of genes. The scientific history of genetics began with the works of Gregor Mendel in the mid-19th century. Prior to Mendel, genetics was primarily theoretical whilst, after Mendel, the science of genetics was broadened to include experimental genetics. Developments in all fields of genetics and genetic technology in the first half of the 20th century provided a basis for the later developments. In the second half of the 20th century, the molecular background of genetics has become more understandable. Rapid technological advancements, followed by the completion of Human Genome Project, have contributed a great deal to the knowledge of genetic factors and their impact on human life and diseases. Currently, more than 1800 disease genes have been identified, more than 2000 genetic tests have become available, and in conjunction with this at least 350 biotechnology-based products have been released onto the market. Novel technologies, particularly next generation sequencing, have dramatically accelerated the pace of biological research, while at the same time increasing expectations. In this paper, a brief summary of genetic history with short explanations of most popular genetic techniques is given.

Capital Controls with International Reserve Accumulation: Can this Be Optimal ?

Motivated by the Chinese experience, we analyze a semi-open economy where the central bank has access to international capital markets, but the private sector has not. This enables the central bank to choose an interest rate different from the international rate. We examine the optimal policy of the central bank by modelling it as a Ramsey planner who can choose the level of domestic public debt and of international reserves. The central bank can improve savings opportunities of credit-constrained consumers modelled as in Woodford (1990). We find that in a steady state it is optimal for the central bank to replicate the open economy, i.e., to issue debt financed by the accumulation of reserves so that the domestic interest rate equals the foreign rate. When the economy is in transition, however, a rapidly growing economy has a higher welfare without capital mobility and the optimal interest rate differs from the international rate. We argue that the domestic interest rate should be temporarily above the international rate. We also find that capital controls can still help reach the first best when the planner has more fiscal instruments.