163 research outputs found
A self-consistent approach to the simulation of ionic motion in open ion channels
No full textIn this thesis, we develop the theoretical and numerical foundations for a self-consistent model for the simulation of the properties of ion channels - their conductivity and selectivity - from their structure. We begin by revising the one-dimensional theory of the ionic current by setting up the self-consistent coupled Langevin Poisson equations in one-dimension, as a prototype of the three dimensional simulations. The solution of a one-dimensional approximation of the Poisson's equation for a channel modelled as a long and narrow cylindrical tube is derived. Using this solution, we calculate the ion trajectory as it traverses the channel.EThOS - Electronic Theses Online ServiceGBUnited Kingdo
Estimating selection pressures on HIV-1 using phylogenetic likelihood models
No full textHuman immunodeficiency virus (HIV-1) can rapidly evolve due to selection pressures exerted by HIV-specific immune responses, antiviral agents, and to allow the virus to establish infection in different compartments in the body. Statistical models applied to HIV-1 sequence data can help to elucidate the nature of these selection pressures through comparisons of non-synonymous (or amino acid changing) and synonymous (or amino acid preserving) substitution rates. These models also need to take into account the non-independence of sequences due to their shared evolutionary history. We review how we have developed these methods and have applied them to characterize the evolution of HIV-1 in vivo. To illustrate our methods, we present an analysis of compartment-specific evolution of HIV-1 em) in blood and cerebrospinal fluid and of site-to-site variation in the gag gene of subtype C HIV-1. Copyright (C) 2008 John Wiley & Sons, Ltd
Non-equilibrium stochastic dynamics of open ion channels
No full textWe present and discuss a modified version of reaction rate theory (RRT) to describe the passage of a positive ion through a biological ion channel. It takes explicit account of the non-equilibrium nature of the permeation process. Unlike traditional RRT, it allows for the non-constant transition rates that arise naturally in an archetypal model of an ion channel. In particular, we allow for the fact that the average escape time of an ion trapped at the selectivity filter (SF) can be reduced substantially by the pair correlations between ions: the arrival of a second ion at the channel entrance significantly reduces the potential barrier impeding the escape of the ion from the SF. The effects of this rate modulation on the current- voltage and current-concentration characteristics of the channel are studied parametrically. Stochastic amplification of the channel conductivity by charge fluctuations is demonstrated and compared with the results of Brownian dynamics simulations
The heroic illusion : Rodrigue and the tragic hero representation in the early 17th century
No full textLe point de départ de ce travail réside d’une part dans la découverte d’une différence considérable de nature entre le héros du Cid et les protagonistes du théâtre contemporain ; et d’autre part sur l’intuition que l’analyse littéraire utilise presque exclusivement Rodrigue comme personnage représentatif du premier XVIIe siècle. Notre première démarche a été de chercher à confirmer ces impressions en démontrant le statut particulier de ce personnage. Nous avons étudié la réception du Cid et de son héros au fil des siècles dans cette optique, jugeant que les réactions des spectateurs, des lecteurs et des critiques construisaient progressivement notre image actuelle de Rodrigue. Nous avons cherché à voir comment depuis janvier 1637 jusqu’au début du XXIe siècle la pièce et son héros ont été accueillis. Nous avons ainsi établi la longévité du texte, ainsi que les exceptionnelles réactions d’engouement qu’il a pu rencontrer. Cela nous a permis d’établir la mythification de la pièce et de dégager sa portée universelle. Ces premières conclusions nous ont invité à rechercher les causes d’un tel succès. C’est à nouveau l’étude de la réception qui nous a permis de découvrir que cette unanimité tenait essentiellement au personnage de Rodrigue. C’est lui qui semble d’abord retenir l’intérêt des lecteurs et des spectateurs. Nous avons donc cherché dans une deuxième partie à comprendre ce qui fascinait tant en Rodrigue. Pour cette raison, nous l’avons confronté à l’idée de héros. La coïncidence saisissante que les réactions publiques révèlent entre ce personnage archétypal et le protagoniste du Cid nous a permis d’aboutir à un premier stade de compréhension : la pièce est accueillie avec enthousiasme au XVIIe siècle parce que son personnage principal actualise l’idéal humain tel que l’époque se le représente. Cependant, l’engouement des siècles suivants repose sur le même motif : c’est parce que Rodrigue incarne le héros du XVIIe siècle que le spectateur du siècle des Lumières, du Romantisme, de la Troisième République ou de l’entre-deux-guerres l’apprécie. Le protagoniste du Cid apparaît comme un héros révéré mais regretté car appartenant à une époque révolue. Au sein de l’œuvre de Corneille, il est également envisagé comme un paradigme héroïque et incarne le modèle dont tous les personnages masculins du théâtre cornélien ne seraient que la déclinaison. Il est l’élément fondateur du mythe du « héros cornélien ». Cependant, l’unanimité de réception face à Rodrigue pose question : Le Cid a-t-il réellement eu une place à part sur le théâtre du premier XVIIe siècle ? À l’ouverture de notre troisième partie, une brève étude de ce théâtre permet de révéler l’écart entre l’image de Rodrigue façonnée par la réception et la réalité dramaturgique des années 1630-1650. La tragi-comédie de Corneille n’est pas la seule pièce à connaître le succès et son héros n’est pas l’unique incarnation sur scène de l’homme tel qu’on se le représente alors. De nombreux autres dramaturges connaissent de réelles réussites. Toutefois, la réception critique les oublie. L’histoire littéraire semble ne vouloir retenir que Corneille pour la postérité. Elle impose Le Cid comme pièce modèle ; mais, se faisant, elle fausse l’appréciation que nous nous faisons du théâtre et des mentalités du XVIIe siècle. Nombre de théories critiques se sont en effet élaborées sur l’idée d’un premier XVIIe siècle glorieux à l’image de Rodrigue et d’une seconde moitié de siècle déclinante et sombre. C’est le cas de Paul Bénichou et de sa « démolition du héros ». Mais peut-on en garantir la véracité si elles reposent pour affirmer la grandeur des premières décennies du siècle sur le seul exemple de Rodrigue ? Une relecture de la littérature de cette période permet pour finir de revenir sur des conceptions altérées notamment par l’éclat du succès incomparable du Cid et d’envisager le premier XVIIe siècle sous une autre lumière.The basis of this work lies primarily in the discovery of a huge nature difference between the hero in “Le Cid”, and the far less glorious contemporary drama protagonists. On the other hand, it is based upon the intuition that most literary analysis almost exclusively use Rodrigue as the character of the first decades of the17th century.The first step of our work was therefore to try to confirm these impressions by conveying the very special status of this character. We have studied the treatment of “Le Cid” and its hero throughout the centuries with this goal in mind, assessing that the way audiences, readers and critics reacted to the play steadily built our perception of Rodrigue. We have tried to understand how the play and its hero were welcomed from January 1637 to the outcome of the 21st century. We have thus established the longevity of the text as well as the outstanding praise reactions it met with. This enabled us to substantiate the mythification of the play and bring into light its universal scope.From these first conclusions, we then tried to find out the reasons why the success of the play has never been denied. Here again it is the study of the critic treatment that quickly showed us that the unanimous public feeling was essentially due to Rodrigue as a character. For it is he mainly who seems to captivate the audience and the readers’interest. In the second part, we therefore tried to understand why Rodrigue is so mesmerising. With this purpose in mind, we confronted our character to the very hero notion. The stiking coincidence that public reactions convey between this archetypal character and “Le Cid” protagonist brought us to a first conclusion: the play is enthusiastically welcomed in the 17th century because the main character updates the human ideal as it was viewed at the time. Yet, the passion that the play generated in later periods is based on the same principle: it is because Rodrigue embodies the 17th century hero that the public from the age of enlightenment, from the great romantic era, from the French 3rd Republic or the interwar period do feel fond of him. “Le Cid” protagonist appears both as a revered and missed hero because he belongs to days gone by, a past example of the ideal man. In Corneille’s entire works, he is also regarded as a heroic paradygm and is viewed as the Cornelian male reference from which other male characters are derived in the works of the playwright. He is the very source of “the Cornelian hero” myth.However, Rodrigue’s unanimous critic treatment brings forward another issue: does “Le Cid” really stand apart in the early 17th century drama? At the outset of our third part, a brief survey of the period drama reveals the gap between Rodrigue’s image as it was made by the critic treatment and the dramatic reality of the 1630-1650 era. Corneille’s tragicomedy is not the only successful play and its hero is not the only stage embodiment of the male figure as it was then represented. Several other playwrights were successful too. Yet, the critic treatment does not take them into account. It seems as if Corneille is the only author to be remembered in the history of literature. Thus, “Le Cid” is the play reference. But it alters our vision of the 17th century drama and mentalities.In fact, scores of critic theories were based on the idea of a glorious early 17th century (impersonated by Rodrigue) as opposed to a gloomier and declining period at the end of the century. But can one guarantee their truthfulness if they are only based on the character of Rodrigue to assert the grandeur of the early 17th century decades?To conclude, a precise and detailed reading of the period literature allows one to study many misinterpretations, particularly because of “Le Cid” unmatched success, and to consider the early 17th century with a brand new perspective
Stochastic dynamics of remote knock-on permeation in biological ion channels
No full textBrownian dynamics simulations provide evidence for a remote knock-on mechanism facilitating the permeation of a biological ion channel by an ion that is initially trapped at the selectivity filter (SF). Unlike the case of conventional direct knock-on, the second ion that instigates permeation does not need to enter the channel. Nor does it necessarily take the place of the permeating ion at the SF, and it can even be of a different ionic species. The study is based on the simultaneous, self-consistent, solution of the coupled Poisson and Langevin equations for a simple generic model, taking account of all the charges present. The new permeation mechanism involves electrostatic amplification attributable to the permittivity mismatch between water and protein: the arrival of the instigating ion at the channel entrance reduces the exit barrier for the ion trapped at the SF, facilitating escape
Dolores Turmel-Rodrigue, peintre de la vie populaire en Beauce
No full textDécédée en 2011 à l’âge de 82 ans, Dolores Turmel-Rodrigue, artiste peintre, s’était donné pour mission de faire revivre dans ses tableaux les personnes, les lieux et les pratiques de la société traditionnelle de sa région natale, la Beauce. Pour nous la présenter et commenter son oeuvre, Bernard Genest a ressorti ses notes de terrain et des enregistrements réalisés dans le cadre de recherches menées dans les années 1982-1985. Il commence par situer l’artiste dans ses contextes géographique, social et culturel, puis s’attarde à décrire la technique et les thématiques qui caractérisent la production de l’artiste. Sans avoir au départ de plan préconçu, celle-ci voyait comme un devoir de mémoire le fait de témoigner de pratiques et d’un mode de vie pour lesquels elle éprouvait un vif attachement et la conviction profonde d’un héritage à préserver et à transmettre. Son oeuvre, selon l’auteur de l’article, est une contribution importante au patrimoine culturel des Beaucerons et pour l’ensemble des Québécois.Passing away in 2011 at the age of 82 years old, Dolores Turmel-Rodrigue, a painter, had assigned herself the task to revive in her paintings the people, places and practices of the traditional society of her native region, Beauce. To represent her and to comment on her work, Bernard Genest took out his field notes and recordings conducted during his research carried out between 1982 and 1985. He begins by situating the artist in her geographical, social and cultural context, and lingers to describe the techniques and themes that characterize the artist’s creations. Departing without a preconceived plan, she saw it as her duty to remember and to testify of the practices and the lifestyle to which she felt a strong commitment, and held strong beliefs to preserve and transmit that legacy. Her work, according to the author of this article, is an important contribution to the cultural heritage of Beauce and for all Quebecers
Self-organized enhancement of conductivity in biological ion channels
No full textWe discuss an example of self-organization in a biological system. It arises from long-range ion–ion interactions, and it leads us to propose a new kind of enhanced conduction in ion channels. The underlying mechanism involves charge fluctuations near the channel mouth, amplified by the mismatch between the relative permittivities of water and the protein of the channel walls. We use Brownian dynamics simulations to show that, as in conventional 'knock on' permeation, these interactions can strongly enhance the channel current; but unlike the conventional mechanism, the enhancement occurs without the instigating bath ion entering the channel. The transition between these two mechanisms is clearly demonstrated, emphasizing their distinction. A simple model accurately reproduces the observed phenomena. We point out that electrolyte plus protein of low relative permittivity are universal in living systems, so that long-range ion–ion correlations of the kind considered must be common
Who wrote the Ladino Siddur for Women [French National Library, Hebr. 668]?
No full textLazar published Siddur Tefillot: A Woman's Ladino Prayer Book in 1995, based on a manuscript found in the French National Library [Hebr. 668]. He claimed that the text originated in 15th century Spain. Minervini reviewed the publication in 1998 and argued that the manuscript must have been written later, most likely in the latter years of the sixteenth or beginning of the seventeenth century. Both researchers agree that the Siddur is a literal, non-normative translation of a Hebrew Siddur written by an amateur author. The bibliographical description of the manuscript gives its origin as “Maroc?.” The manuscript is extremely interesting because it features linguistic characteristics of the languages spoken in Andalusia, Aragon, Portugal, Italy, and Judeo-Spanish from the Ottoman Empire. This paper examines various linguistic and textual aspects of the Siddur to determine the origin of the author. Even if the manuscript did reach Paris via Morocco, the linguistic data prove that the author's background is from Italy, probably of Portuguese ex-converso origin
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