Le vrai est-il un objet? Remarques sur l'analogie entre nom propre et énoncé dans la théorie de la signification de Frege.

12 pagesThis article is meant as an introduction to some problems raised by Frege's conception of truth. We are mainly concerned with the motivations of the thesis that considers truth-values as objects. We question the analogy principle that guides Frege as he sets up his semantics. With the sole criterium of insaturation, Frege classifies linguistic expressions and their corresponding entities. This criterium furthers the analogy between proper noun and sentence, that is pushed to identification. In a first step, we expound the general features of the fregean semantics, before scrutinising the role played by the true in the exposition of the formalism of Basic laws of arithmetics.Cet article se veut une introduction à quelques-uns des problèmes soulevés par la conception frégéenne de la vérité. Notre intérêt se porte principalement sur les motivations de la thèse des valeurs de vérité comme objets. Nous questionnons le principe d'analogie qui guide Frege dans l' établissement de sa sémantique. A l' aide d'un critère unique, l'insaturation, Frege classe les expressions linguistiques et les entités qui leur correspondent. Ce critère favorise l' analogie entre nom propre et énoncé, analogie qui est poussée jusqu'à l' assimilation. Dans un premier temps, nous exposons les traits généraux de la sémantique frégéenne, puis nous étudions le rôle que joue le vrai dans l'exposition du formalisme des Lois fondamentales de l' arithmétique

Regulation of fibroblast migration by tenascin-C

Abstract Synthesis of new tissue by fibroblasts is required for tissue rebuilding in response to injury. Fibroblast migration from surrounding healthy tissue into the fibrin-fibronectin provisional matrix deposited upon injury is a key rate-limiting step of this stage of tissue repair. These events must be tightly regulated. Excessive deposition of scar tissue is the major hallmark of fibrotic disease. Tenascin-C is an extracellular matrix glycoprotein that is transiently expressed upon tissue injury, where it is specifically localized to the wound edge, and persistently up-regulated in fibrotic disease. We have shown that full-length tenascin-C promotes fibroblast migration within fibrin-fibronectin matrices and we have mapped the domains within the molecule critical for enhancing migration. We also demonstrated that specific fragments of tenascin-C inhibit fibroblast migration. These results suggest that transient expression of tenascin-C at the wound boundary is key to tissue repair: its induction recruits fibroblasts into the wound and fragments resulting from its breakdown prevent excessive fibroblast infiltration. Our results demonstrate how fibroblast migration in three-dimensional provisional matrices may be differentially regulated by proteolysis of matrix molecules and could explain how persistent expression of tenascin-C contributes to the progression of fibrotic disease

Probabilistic functional tractography of the human cortex revisited

In patients with pharmaco-resistant focal epilepsies investigated with intracranial electroencephalography (iEEG), direct electrical stimulations of a cortical region induce cortico-cortical evoked potentials (CCEP) in distant cerebral cortex, which properties can be used to infer large scale brain connectivity. In 2013, we proposed a new probabilistic functional tractography methodology to study human brain connectivity. We have now been revisiting this method in the F-TRACT project (f-tract.eu) by developing a large multicenter CCEP database of several thousand stimulation runs performed in several hundred patients, and associated processing tools to create a probabilistic atlas of human cortico-cortical connections. Here, we wish to present a snapshot of the methods and data of F-TRACT using a pool of 213 epilepsy patients, all studied by stereo-encephalography with intracerebral depth electrodes. The CCEPs were processed using an automated pipeline with the following consecutive steps: detection of each stimulation run from stimulation artifacts in raw intracranial EEG (iEEG) files, bad channels detection with a machine learning approach, model-based stimulation artifact correction, robust averaging over stimulation pulses. Effective connectivity between the stimulated and recording areas is then inferred from the properties of the first CCEP component, i.e. onset and peak latency, amplitude, duration and integral of the significant part. Finally, group statistics of CCEP features are implemented for each brain parcel explored by iEEG electrodes. The localization (coordinates, white/gray matter relative positioning) of electrode contacts were obtained from imaging data (anatomical MRI or CT scans before and after electrodes implantation). The iEEG contacts were repositioned in different brain parcellations from the segmentation of patients' anatomical MRI or from templates in the MNI coordinate system. The F-TRACT database using the first pool of 213 patients provided connectivity probability values for 95% of possible intrahemispheric and 56% of interhemispheric connections and CCEP features for 78% of intrahemisheric and 14% of interhemispheric connections. In this report, we show some examples of anatomo-functional connectivity matrices, and associated directional maps. We also indicate how CCEP features, especially latencies, are related to spatial distances, and allow estimating the velocity distribution of neuronal signals at a large scale. Finally, we describe the impact on the estimated connectivity of the stimulation charge and of the contact localization according to the white or gray matter. The most relevant maps for the scientific community are available for download on f-tract. eu (David et al., 2017) and will be regularly updated during the following months with the addition of more data in the F-TRACT database. This will provide an unprecedented knowledge on the dynamical properties of large fiber tracts in human.Peer reviewe

The role of tenascin-C in tissue injury and tumorigenesis

The extracellular matrix molecule tenascin-C is highly expressed during embryonic development, tissue repair and in pathological situations such as chronic inflammation and cancer. Tenascin-C interacts with several other extracellular matrix molecules and cell-surface receptors, thus affecting tissue architecture, tissue resilience and cell responses. Tenascin-C modulates cell migration, proliferation and cellular signaling through induction of pro-inflammatory cytokines and oncogenic signaling molecules amongst other mechanisms. Given the causal role of inflammation in cancer progression, common mechanisms might be controlled by tenascin-C during both events. Drugs targeting the expression or function of tenascin-C or the tenascin-C protein itself are currently being developed and some drugs have already reached advanced clinical trials. This generates hope that increased knowledge about tenascin-C will further improve management of diseases with high tenascin-C expression such as chronic inflammation, heart failure, artheriosclerosis and cancer

Développement d'outils de traitement du signal et statistiques pour l'analyse de groupe des réponses induites par des stimulations électriques corticales directes chez l'humain

Introduction: Low-frequency direct electrical stimulation is performed in drug-resistant epileptic patients, implanted with depth electrodes. It induces cortico-cortical evoked potentials (CCEP) that allow in vivo connectivity mapping of local networks. The multicentric project F-TRACT aims at gathering data of several hundred patients in a database to build a propabilistic functional tractography atlas that estimates connectivity at the cortex level.Methods: Semi-automatic processing pipelines have been developed to handle the amount of stereo-electroencephalography (SEEG) and imaging data and store them in a database. New signal processing and machine-learning methods have been developed and included in the pipelines, in order to automatically identify bad channels and correct the stimulation artifact. Group analyses have been performed using CCEP features and time-frequency maps of the stimulation responses.Results: The new methods performance has been assessed on heterogeneous data, coming from different hospital center recording and stimulating using variable parameters. The atlas was generated from a sample of 173 patients, providing a connectivity probability value for 79% of the possible connections and estimating biophysical properties of fibers for 46% of them. The methodology was applied on patients who experienced auditory symptoms that allowed the identification of different networks involved in hallucination or illusion generation. Oscillatory group analysis showed that anatomy was driving the stimulation response pattern.Discussion: A methodology for CCEP study at the cerebral cortex scale is presented in this thesis. Heterogeneous data in terms of acquisition and stimulation parameters and spatially were used and handled. An increasing number of patients’ data will allow the maximization of the statistical power of the atlas in order to study causal cortico-cortical interactions.Introduction : La stimulation électrique directe basse fréquence est pratiquée sur des patients épileptiques pharmaco-résistants implantés avec des électrodes profondes. Elle induit de potentiels évoqués cortico-corticaux (PECC) qui permettent d’estimer la connectivité in vivo et ont permis de caractériser des réseaux locaux. Pour estimer la connectivité à l’échelle du cortex, le projet multicentrique F-TRACT vise à rassembler plusieurs centaines de patients dans une base de données pour proposer un atlas probabiliste de tractographie fonctionnelle.Méthodes : La construction de la base de données à nécessité la mise en place technique de pipelines de traitement semi-automatiques pour faciliter la gestion du nombre important de données de stéréo-électroencéphalographie (SEEG) et d’imagerie. Ces pipelines incluent des nouvelles méthodes de traitement du signal et d’apprentissage automatique, qui ont été développées pour identifier automatiquement les mauvais contacts et corriger l’artefact induit par la stimulation. Les analyses de groupe se sont basées sur des métriques des PECC et des cartes temps-fréquences des réponses à la stimulation.Résultats : La performance des méthodes développées pour le projet a été validée sur des données hétérogènes, en termes de paramètres d’acquisition et de stimulation, provenant de différents centres hospitaliers. L’atlas a été généré à partir d’un échantillon de 173 patients, fournissant une mesure de probabilité de connectivité pour 79% des connexions et d’estimer des propriétés biophysiques des fibres pour 46% d’entre elles. Son application à une sous-population de patients a permis d’étudier les réseaux impliqués dans la génération de symptômes auditifs. L’analyse de groupe oscillatoire a mis en avant l’influence de l’anatomie sur la réponse à la stimulation.Discussion : Cette thèse présente une méthodologie d’étude des PECC à l’échelle du cortex cérébral, utilisant des données hétérogènes en termes d’acquisition, de paramètres de stimulation et spatialement. L’incrémentation du nombre de patients dans l’atlas généré permettra d’étudier les interactions cortico-corticales de manière causale

Sense, reference, conceptual script : studies on Frege

Notre travail de thèse aborde la question suivante : quel est le thème de l'idéographie frégéenne ? Nous y répondons en questionnant l'emploi de la terminologie modèle-théorique ordinairement employée. Notre méthode consiste en un examen détaillé des Grundgesetze, ainsi qu'en une approche comparative avec les œuvres de deux objecteurs contemporains de Frege, le Tractatus-logico philosophicus de Wittgenstein et les Fondements de la géométrie de Hilbert. Pour déterminer ce dont traite l'idéographie, il faut envisager la manière dont sont rendues signifiantes les expressions qu'elle contient. En vue de répondre à cette question, un examen du statut des notions de sens et de référence est accompli, au niveau épistémique, correspondant à la compréhension par un locuteur, ainsi qu'au niveau théorique, concernant leur place précise dans le compte-rendu des démonstrations en langage idéographique. Les notions de sens et de référence sont expliquées par des éclaircissements : leur introduction est déjà leur mise en œuvre. Nous privilégions une lecture interne de ces notions. Au centre de notre travail se trouve le défi formaliste : peut-on conjuguer l'idéal d'une corrélation bi-univoque entre signes et sens et l'exigence d'une pluralité de signes de même sens, nécessaire aux définitions ? Nous montrons que la distinction entre sens et référence conserve un rôle opératoire dans l'idéographie, qu'elle illustre la fécondité démonstrative du système, ce qui a peu été souligné jusqu'à présent dans les études frégéennes. Ainsi il est possible de défendre Frege face à ce défi en soutenant que la diversité des sens, même corrélée à la diversité des signes, ne lui est pas réductible.Our doctoral thesis addresses the following question : what is the theme of the fregean conceptual script? We answer it in questioning the model-theoretical framework currently used. Our method consists in a close study of the fregean texts, especially the Grundgesetze, and in a comparative approach with the works of two contemporary critics of Frege, the Tractatus logico-philosophicus by Wittgenstein and the Foundations of geometry by Hilbert. To determine what the fregean conceptual script is about, we have to consider how the expressions it contains are made significant. For that purpose, a close examination of the notions of sense and reference is carried out, at the epistemic level, that corresponds to the understanding by a speaker, and at the theoretic level, that concerns the role it plays in the account of proofs in the conceptual script. Frege explains the notions of sense and reference through elucidations: their introduction is already part of their use. We favour an internal reading of these notions.Crucial in our work is what we reconstruct as a formalist challenge addressed to Frege: is it possible to combine the ideal of a one-one correlation between signs and senses with the demand of a plurality of signs with the same sense, necessary for the purpose of definitions? We show that the distinction between sense and reference retains an operative role in the conceptual script, that it highlights the fecundity of the system, which has seldom been underlined in the fregean studies. Thus we argue that Frege can face that formalist challenge, because the plurality of senses, even when it is correlated with the plurality of signs, cannot be reduced to it