Changements guidés par les buts en argumentation : Cadre théorique et outil

National audienceCet article définit un cadre théorique pour étudier le changement en argumentation. Ce cadre permet de prendre en compte le raisonnement d’un agent qui désire modifier un système d’argumentation cible afin d’atteindre certains buts. Les modifications sont des ajouts/retraits d’arguments ou d’attaques. L’agent est contraint par ses propres connaissances représentées par un deuxième système d’argumentation. Nous présentons un logiciel capable de calculer les opérations exécutables par un agent pour atteindre ses buts sur une cible donnée

Goal-driven Changes in Argumentation: A theoretical framework and a tool

International audienceThis paper defines a new framework for dynamics in argumentation. In this framework, an agent can change an argumentation system (the target system) in order to achieve some desired goal. Changes consist in addition/removal of arguments or attacks between arguments and are constrained by the agent’s knowledge encoded by another argumentation system. We present a software that computes the possible change operations for a given agent on a given target argumentation system in order to achieve some given goal

Argumentation update in YALLA (Yet Another Logic Language for Argumentation)

International audienceThis article proposes a complete framework for handling the dynamics of an abstract argumentation system. This frame can encompass several belief bases under the form of several argumentation systems, more precisely it is possible to express and study how an agent who has her own argumentation system can interact on a target argumentation system (that may represent a state of knowledge at a given stage of a debate). The two argumentation systems are defined inside a reference argumentation system called the universe which constitutes a kind of “common language”. This paper establishes three main results. First, we show that change in argumentation in such a framework can be seen as a particular case of belief update. Second, we have introduced a new logical language called YALLA in which the structure of an argumentation system can be encoded, enabling to express all the basic notions of argumentation theory (defense, conflict-freeness, extensions) by formulae of YALLA. Third, due to previous works about dynamics in argumentation we have been in position to provide a set of new properties that are specific for argumentation update

À propos de l’article de Alain-Marie Bassy, un point de vue québécois

Alain-Marie Bassy présente une analyse systémique susceptible de répondre aux interrogations de leaders éducatifs sur la lenteur que connaît l’adoption de l’innovation, reflet de nombre de résistances au changement non-perçu comme nécessaire ou, plutôt, de l’absence de conditions favorables, s’agisse-t-il des outils numériques ou des pratiques pédagogiques et organisationnelles qu’ils servent ou entraînent, dans les systèmes éducatifs francophones et autres. Nous retenons les cinq pistes de réflexion suivantes soumises par Bassy car elles trouvent écho au Québec : a) le modèle industriel (technologies, coûts de production) en évolution rapide ; b) le modèle de gouvernance : prééminence de l’État, centralisation et prescription ; c) le modèle social de l'École : de Jules Ferry au numérique, la mise en cause des dogmes ; d) le modèle pédagogique : les missions et le service de l'enseignant, immuables? e) le modèle éditorial et commercial : de l'imprimé au numérique, continuité ou rupture ? Notre réaction est ancrée dans les travaux que nous menons en tant que membres du Centre de recherche et d’intervention sur la réussite scolaire (CRIRES, crires.ulaval.ca) dont l’activité vise l’innovation sous l’éclairage, entre autres, du modèle d’Engeström (Engeström, 1987) ; (Engeström, 2010), en tant que membres du CEFRIO (cefrio.qc.ca), centre facilitant la recherche et l’innovation dans les organisations à l’aide des TIC, ou du CTREQ (ctreq.qc.ca), centre qui a pour mission de promouvoir l'innovation et le transfert de connaissances en vue d’accroître la réussite éducative du Québec

Abasic and oxidized ribonucleotides embedded in DNA are processed by human APE1 and not by RNase H2

Ribonucleoside 5'-monophosphates (rNMPs) are the most common non-standard nucleotides found in DNA of eukaryotic cells, with over 100 million rNMPs transiently incorporated in the mammalian genome per cell cycle. Human ribonuclease (RNase) H2 is the principal enzyme able to cleave rNMPs in DNA. Whether RNase H2 may process abasic or oxidized rNMPs incorporated in DNA is unknown. The base excision repair (BER) pathway is mainly responsible for repairing oxidized and abasic sites into DNA. Here we show that human RNase H2 is unable to process an abasic rNMP (rAP site) or a ribose 8oxoG (r8oxoG) site embedded in DNA. On the contrary, we found that recombinant purified human apurinic/apyrimidinic endonuclease-1 (APE1) and APE1 from human cell extracts efficiently process an rAP site in DNA and have weak endoribonuclease and 3'-exonuclease activities on r8oxoG substrate. Using biochemical assays, our results provide evidence of a human enzyme able to recognize and process abasic and oxidized ribonucleotides embedded in DNA

NMR structure and ion channel activity of the p7 protein from hepatitis C virus

The small membrane protein p7 of hepatitis C virus forms oligomers and exhibits ion channel activity essential for virus infectivity. These viroporin features render p7 an attractive target for antiviral drug development. In this study, p7 from strain HCV-J (genotype 1b) was chemically synthesized and purified for ion channel activity measurements and structure analyses. p7 forms cation-selective ion channels in planar lipid bilayers and at the single-channel level by the patch clamp technique. Ion channel activity was shown to be inhibited by hexamethylene amiloride but not by amantadine. Circular dichroism analyses revealed that the structure of p7 is mainly α-helical, irrespective of the membrane mimetic medium (e.g. lysolipids, detergents, or organic solvent/water mixtures). The secondary structure elements of the monomeric form of p7 were determined by 1H and 13C NMR in trifluoroethanol/water mixtures. Molecular dynamics simulations in a model membrane were combined synergistically with structural data obtained from NMR experiments. This approach allowed us to determine the secondary structure elements of p7, which significantly differ from predictions, and to propose a three-dimensional model of the monomeric form of p7 associated with the phospholipid bilayer. These studies revealed the presence of a turn connecting an unexpected N-terminal α-helix to the first transmembrane helix, TM1, and a long cytosolic loop bearing the dibasic motif and connecting TM1 to TM2. These results provide the first detailed experimental structural framework for a better understanding of p7 processing, oligomerization, and ion channel gating mechanism.Instituto de Física La Plat

Rab27A and its effector MyRIP link secretory granules to F-actin and control their motion towards release sites

The GTPase Rab27A interacts with myosin-VIIa and myosin-Va via MyRIP or melanophilin and mediates melanosome binding to actin. Here we show that Rab27A and MyRIP are associated with secretory granules (SGs) in adrenal chromaffin cells and PC12 cells. Overexpression of Rab27A, GTPase-deficient Rab27A-Q78L, or MyRIP reduced secretory responses of PC12 cells. Amperometric recordings of single adrenal chromaffin cells revealed that Rab27A-Q78L and MyRIP reduced the sustained component of release. Moreover, these effects on secretion were partly suppressed by the actin-depolymerizing drug latrunculin but strengthened by jasplakinolide, which stabilizes the actin cortex. Finally, MyRIP and Rab27A-Q78L restricted the motion of SGs in the subplasmalemmal region of PC12 cells, as measured by evanescent-wave fluorescence microscopy. In contrast, the Rab27A-binding domain of MyRIP and a MyRIP construct that interacts with myosin-Va but not with actin increased the mobility of SGs. We propose that Rab27A and MyRIP link SGs to F-actin and control their motion toward release sites through the actin cortex

NMR structure and ion channel activity of the p7 protein from hepatitis C virus

The small membrane protein p7 of hepatitis C virus forms oligomers and exhibits ion channel activity essential for virus infectivity. These viroporin features render p7 an attractive target for antiviral drug development. In this study, p7 from strain HCV-J (genotype 1b) was chemically synthesized and purified for ion channel activity measurements and structure analyses. p7 forms cation-selective ion channels in planar lipid bilayers and at the single-channel level by the patch clamp technique. Ion channel activity was shown to be inhibited by hexamethylene amiloride but not by amantadine. Circular dichroism analyses revealed that the structure of p7 is mainly α-helical, irrespective of the membrane mimetic medium (e.g. lysolipids, detergents, or organic solvent/water mixtures). The secondary structure elements of the monomeric form of p7 were determined by 1H and 13C NMR in trifluoroethanol/water mixtures. Molecular dynamics simulations in a model membrane were combined synergistically with structural data obtained from NMR experiments. This approach allowed us to determine the secondary structure elements of p7, which significantly differ from predictions, and to propose a three-dimensional model of the monomeric form of p7 associated with the phospholipid bilayer. These studies revealed the presence of a turn connecting an unexpected N-terminal α-helix to the first transmembrane helix, TM1, and a long cytosolic loop bearing the dibasic motif and connecting TM1 to TM2. These results provide the first detailed experimental structural framework for a better understanding of p7 processing, oligomerization, and ion channel gating mechanism.Instituto de Física La Plat

A collaborative model to implement flexible, accessible and efficient oncogenetic services for hereditary breast and ovarian cancer : the C-MOnGene study

Medical genetic services are facing an unprecedented demand for counseling and testing for hereditary breast and ovarian cancer (HBOC) in a context of limited resources. To help resolve this issue, a collaborative oncogenetic model was recently developed and implemented at the CHU de Québec-Université Laval; Quebec; Canada. Here, we present the protocol of the C-MOnGene (Collaborative Model in OncoGenetics) study, funded to examine the context in which the model was implemented and document the lessons that can be learned to optimize the delivery of oncogenetic services. Within three years of implementation, the model allowed researchers to double the annual number of patients seen in genetic counseling. The average number of days between genetic counseling and disclosure of test results significantly decreased. Group counseling sessions improved participants' understanding of breast cancer risk and increased knowledge of breast cancer and genetics and a large majority of them reported to be overwhelmingly satisfied with the process. These quality and performance indicators suggest this oncogenetic model offers a flexible, patient-centered and efficient genetic counseling and testing for HBOC. By identifying the critical facilitating factors and barriers, our study will provide an evidence base for organizations interested in transitioning to an oncogenetic model integrated into oncology care; including teams that are not specialized but are trained in genetics

Lesion-induced DNA weak structural changes detected by pulsed EPR spectroscopy combined with site-directed spin labelling

Double electron-electron resonance (DEER) was applied to determine nanometre spin–spin distances on DNA duplexes that contain selected structural alterations. The present approach to evaluate the structural features of DNA damages is thus related to the interspin distance changes, as well as to the flexibility of the overall structure deduced from the distance distribution. A set of site-directed nitroxide-labelled double-stranded DNA fragments containing defined lesions, namely an 8-oxoguanine, an abasic site or abasic site analogues, a nick, a gap and a bulge structure were prepared and then analysed by the DEER spectroscopic technique. New insights into the application of 4-pulse DEER sequence are also provided, in particular with respect to the spin probes’ positions and the rigidity of selected systems. The lesion-induced conformational changes observed, which were supported by molecular dynamics studies, confirm the results obtained by other, more conventional, spectroscopic techniques. Thus, the experimental approaches described herein provide an efficient method for probing lesion-induced structural changes of nucleic acids