166 research outputs found
Altération du voisement dans l'aphasie : analyses acoustiques des substitutions d'un aphasique de Broca
International audienceDe nombreuses Ă©tudes ont montrĂ© des tendances prĂ©fĂ©rentielles quant aux substitutions produites par des aphasiques de Broca, de Conduction et de Wernicke dans diffĂ©rentes langues ([8], [3], [9], [7], [12], [6]). Le dĂ©voisement des obstruantes par exemple est trĂšs frĂ©quent et peut indiquer une perte du contraste phonologique du voisement. Cependant, dans ces Ă©tudes les substitutions ont Ă©tĂ© relevĂ©es sur une base perceptive. Or, l'analyse perceptive Ă©tant biaisĂ©e par le systĂšme perceptif du transcripteur, certains auteurs l'ont complĂ©tĂ©e avec des analyses acoustiques, notamment avec les valeurs du Voice Onset Time (VOT), principalement en anglais et en espagnol ([4], [2], [10], [11]). Il semblerait qu'il n'existe que trĂšs peu d'Ă©tudes similaires portant sur le français Ă notre connaissance ([1], [14], [16]). Les analyses acoustiques permettent de prĂ©ciser le niveau du dĂ©voisement : cette perte de contraste peut ĂȘtre due Ă une atteinte du systĂšme phonologique, ou Ă des rĂ©alisations phonĂ©tiques non standard des sons. La prĂ©sente Ă©tude cherche Ă approfondir cette question en apportant de nouvelles analyses acoustiques sur de nouvelles donnĂ©es d'aphasiques en français Ă la suite d'analyses phonologiques. Les premiers rĂ©sultats portent sur les productions d'un patient aphasique de Broca francophone monolingue de 65 ans, enregistrĂ© au sein d'un centre de soins de suite et rĂ©adaptation en rĂ©gion parisienne. Le protocole est composĂ© d'une tĂąche de rĂ©pĂ©tition et de dĂ©nomination d'images de 64 mots bi-et uni-syllabiques de formes CVC(V)(C) pour lesquels l'effet de frĂ©quence lexicale a Ă©tĂ© neutralisĂ©. Les obstruantes se trouvent en position d'attaque suivies des voyelles cardinales /a, i, u/ et de /ÉÌ /, puis en position de coda prĂ©cĂ©dĂ©es d'une de ces voyelles. Nous prĂ©sentons ici les analyses acoustiques pour la tĂąche de rĂ©pĂ©tition, celles concernant la tĂąche de dĂ©nomination Ă©tant en cours d'analyse. Une transcription perceptive de ces donnĂ©es a Ă©tĂ© effectuĂ©e sous PHON [13] par l'auteur, puis vĂ©rifiĂ©e par une double transcription. En cas de dĂ©saccord, le spectrogramme et le signal acoustique ont Ă©tĂ© visualisĂ©s afin de dĂ©cider de la transcription adĂ©quate. Enfin, une segmentation manuelle du signal a permis d'extraire, Ă l'aide d'un script Praat [5] : la durĂ©e du burst des occlusives, la durĂ©e totale des occlusives voisĂ©es et des fricatives et la durĂ©e de la voyelle prĂ©cĂ©dente le cas Ă©chĂ©ant. Nos premiĂšres analyses sur la durĂ©e des fricatives cibles montrent une diffĂ©rence selon le voisement de la consonne cible : les sourdes (NV) sont en moyenne bien plus longues que les sonores (V). Le tableau 1 montre les durĂ©es des consonnes cibles (//) et leur rĂ©alisation perçue ([]). La durĂ©e du bruit de friction ne semble pas dĂ©terminĂ©e par sa rĂ©alisation phonĂ©tique : /V/ â [NV] 149 ms /NV/ â [NV] 211 ms /V/ â [V] 116 ms /NV/ â [V] 193 ms Tableau 1 : DurĂ©e moyenne des fricatives 94 Posters-Session 02 | Vendredi 30 juin | JPC Paris 201
Quelles donnĂ©es pour lâanalyse phonologique de la parole aphasique ?
Cette Ă©tude se focalise sur diffĂ©rentes mĂ©thodes utilisĂ©es pour lâanalyse phonologique de la parole aphasique. Nous comparons des tĂąches expĂ©rimentales de rĂ©pĂ©tition et de dĂ©nomination dâimage, des tĂąches dâĂ©licitation semi-structurĂ©es et de la parole naturelle. Nous montrons que le type de mots rencontrĂ©s, le type de consonnes ou encore le nombre de productions diffĂšrent selon la tĂąche. Si les protocoles expĂ©rimentaux permettent dâobtenir toutes les cibles voulues, les tĂąches dâĂ©licitation semi-structurĂ©e permettent dâavoir un plus grand nombre dâoccurrences de sons et de mots et des productions subissant des transformations diffĂ©rentes.This study focuses on different methods used for the phonological analysis of aphasic speech. We compare experimental tasks (repetition and picture naming), semi-structured elicitation tasks and natural speech. We show that word types, consonant types and the number of production occurrences vary according to the task. Experimental protocols allow obtaining all wanted targets and semi-structured elicitation tasks allow having a greater number of occurrences of sounds and words, and different segmental transformations
A New Generation of Peptide-based Inhibitors Targeting HIV-1 Reverse Transcriptase Conformational Flexibility.
International audienceThe biologically active form of human immunodeficiency virus (HIV) type 1 reverse transcriptase (RT) is a heterodimer. The formation of RT is a two-step mechanism, including a rapid protein-protein interaction "the dimerization step," followed by conformational changes "the maturation step," yielding the biologically active form of the enzyme. We have previously proposed that the heterodimeric organization of RT constitutes an interesting target for the design of new inhibitors. Here, we propose a new class of RT inhibitors that targets protein-protein interactions and conformational changes involved in the maturation of heterodimeric reverse transcriptase. Based on a screen of peptides derived from the thumb domain of this enzyme, we have identified a short peptide P(AW) that inhibits the maturation step and blocks viral replication at subnanomolar concentrations. P(AW) only binds dimeric RT and stabilizes it in an inactive/non-processive conformation. From a mechanistic point of view, P(AW) prevents proper binding of primer/template by affecting the structural dynamics of the thumb/fingers of p66 subunit. Taken together, these results demonstrate that HIV-1 RT maturation constitutes an attractive target for AIDS chemotherapeutics
Effect of Type-I Interferon on Retroviruses
Type-I interferons (IFN-I) play an important role in the innate immune response to several retroviruses. They seem to be effective in controlling the in vivo infection, though many of the clinical signs of retroviral infection may be due to their continual presence which over-stimulates the immune system and activates apoptosis. IFN-I not only affect the immune system, but also operate directly on virus replication. Most data suggest that the in vitro treatment with IFN-I of retrovirus infected cells inhibits the final stages of virogenesis, avoiding the correct assembly of viral particles and their budding, even though the mechanism is not well understood. However, in some retroviruses IFN-I may also act at a previous stage as some retroviral LTRs posses sequences homologous to the IFN-stimulated response element (ISRE). When stimulated, ISREs control viral transcription. HIV-1 displays several mechanisms for evading IFN-I, such as through Tat and Nef. Besides IFN-α and IFN-ÎČ, some other type I IFN, such as IFN-Ï and IFN-Ï, have potent antiviral activity and are promising treatment drugs
Transient dsDNA breaks during pre-replication complex assembly
Initiation of DNA replication involves the ordered assembly of the multi-protein pre-replicative complex (pre-RC) during G1 phase. Previously, DNA topoisomerase II (topo II) was shown to associate with the DNA replication origin located in the lamin B2 gene locus in a cell-cycle-modulated manner. Here we report that activation of both the early-firing lamin B2 and the late-firing hOrs8 human replication origins involves DNA topo II-dependent, transient, site-specific dsDNA-break formation. Topo IIÎČ in complex with the DNA repair protein Ku associates in vivo and in vitro with the pre-RC region, introducing dsDNA breaks in a biphasic manner, during early and mid-G1 phase. Inhibition of topo II activity interferes with the pre-RC assembly resulting in prolonged G1 phase. The data mechanistically link DNA topo IIÎČ-dependent dsDNA breaks and the components of the DNA repair machinery with the initiation of DNA replication and suggest an important role for DNA topology in origin activation
Inhibitors of retrograde trafficking active against ricin and Shiga toxins also protect cells from several viruses, Chlamydiales and Leishmania
Medical countermeasures to treat biothreat agent infections require broad-spectrum therapeutics that do not induce agent resistance. A cell-based high-throughput screen (HTS) against ricin toxin combined with hit optimization allowed selection of a family of compounds that meet these requirements. The hit compound Retro-2 and its derivatives have been demonstrated to be safe in vivo in mice even at high doses. Moreover, Retro-2 is an inhibitor of retrograde transport that affects syntaxin-5- dependent toxins and pathogens. As a consequence, it has a broad-spectrum activity that has been demonstrated both in vitro and in vivo against ricin, Shiga toxin-producing O104:H4 enterohemorrhagic E. coli and Leishmania sp. and in vitro against Ebola, Marburg and poxviruses and Chlamydiales. An effect is anticipated on other toxins or pathogens that use retrograde trafficking and syntaxin-5. Since Retro-2 targets cell components of the host and not directly the pathogen, no selection of resistant pathogens is expected. These lead compounds need now to be developed as drugs for human use
Aider les étudiants entrant du supérieur à améliorer leurs compétences en français académique
International audienc
Training program for the improvement of writing capabilities in academic environment : major issues and impact on representations and practices : an example with Ă©cri+ project
Cette thĂšse de doctorat sâinscrit dans le cadre du projet Ă©cri+, projet national, sĂ©lectionnĂ© comme Plan dâInvestissement dâAvenir 3 (PIA3), volet Nouveaux Cursus Universitaires (NCU). Ce dispositif mutualisĂ© a pour but dâaider les Ă©tudiants Ă dĂ©velopper leurs compĂ©tences en français Ă©crit Ă lâuniversitĂ©, tant en comprĂ©hension quâen production. Nos recherches sâintĂšgrent plus prĂ©cisĂ©ment dans lâaction numĂ©ro 5 du projet, en charge de lâanalyse dâimpact du dispositif, Ă la croisĂ©e du champ de la didactique du français et de lâusage du numĂ©rique. La pĂ©dagogie universitaire, et plus particuliĂšrement, les dispositifs de formation en lien avec lâamĂ©lioration des compĂ©tences Ă©crites en tant que facteurs de rĂ©ussite Ă lâuniversitĂ© sont au coeur de notre Ă©tude. Nous explorons deux grands axes Ă travers les questions suivantes : quâelles sont les reprĂ©sentations des acteurs impliquĂ©s dans ces dispositifs dâaccompagnement pour lâamĂ©lioration des compĂ©tences Ă©crites en contexte universitaire ? Quelles scĂ©narisations pĂ©dagogiques sont-elles mises en place et quelle rĂ©ception cela entraine-t-il chez les Ă©tudiants ?Notre corpus est constituĂ© de questionnaires Ă destination des enseignants et des Ă©tudiants impliquĂ©s dans lâensemble des dispositifs de Le Mans UniversitĂ©, dâentretiens collectifs menĂ©s avec les enseignants et des traces informatiques extraites de la plateforme de formation en ligne de type Moodle utilisĂ©e dans le cadre de ces enseignements.Nous tentons de proposer, dâaprĂšs les diffĂ©rents rĂ©sultats et analyses obtenus, des pistes didactiques en termes dâingĂ©nierie pĂ©dagogique et dâaccompagnement des enseignants dans ces dispositifs de renforcement des compĂ©tences Ă©crites.This doctoral thesis is part of the Ă©cri+ initiative, a national project selected for the Plan d'Investissement d'Avenir 3 (PIA3), Nouveaux Cursus Universitaires (NCU). This programme is co-produced to help students at University improve their written competencies in French both in their understanding and elaboration. Our research forms part of the section 5 of that project that deep dives the impact of this initiative at the crossroads between French didactics and the use of digital tools and new technologies. University pedagogy and more specifically the ones dedicated to the improvement of writing skills as a factor of success at university, are at the heart of our study.This research answers the following questions : what are the representations of the actors involved in the definition of those support programmes? Which learning scenarios are in place and what is their impact on students ? Our corpus is made of multiple questionnaires developed and addressed to teachers and students participating in this initiative, collective interviews conducted with teachers, and digital records extracted from the Moodle-type online training platform. Based on the various outcomes and analyses achieved, we are recommending pedagogical engineering and supporting didactical guidelines for teachers part of those programmes
- âŠ