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The synthesis and characterization of a range of bis(iminophosphoranyl)phosphide (BIPP) group 4 and coinage metals complexes is reported. BIPP ligands bind group 4 metals in a pseudo fac-fashion, and the central phosphorus atom enables the formation of d0–d10 heterobimetallic complexes. Various DFT computational tools (including AIM, ELF and NCI) show that the phosphorus–metal interaction is either electrostatic (Ti) or dative (Au, Cu). A bridged homobimetallic Cu–Cu complex was also prepared and its spectroscopic properties were investigated. The theoretical analysis of the P–P bond in BIPP complexes reveals that (i) BIPP are closely related to ambiphilic triphosphenium (TP) cations; (ii) the P–P bonds are normal covalent (i.e. not dative) in both BIPP and TP., The synthesis, characterization and computational analysis of a range of bis(iminophosphoranyl)phosphide (BIPP) group 4 and coinage metals complexes is reported. White phosphorus was used to install the central phosphorus atom. more...

Cet article est un compte-rendu du livre : Léo Spitzer, Textes théoriques et méthodologiques, éd. Étienne Karabétian, Genève, Droz, coll. « Titre courant » n° 68, 2019, 400 p., EAN 9782600005685.

International audience; Levels of automation implemented in the railway domain are already high, especially with automated metro. Nevertheless, high levels of automation in the urban sector cannot be directly transposed to train control in mainline or freight sectors, since the train driving environment is more likely to face various unexpected events. The autonomous train is still the final objective; nevertheless, before reaching such a high level of automation, the first step will be to design intermediate levels where human operator is kept in the loop of train control. As for the scope of the TC-Rail project, presented in this paper, the design of remote driving is a necessary first stage that serves two objectives: the optimization of freight railway traffic and a way to recover from an autonomous train, as a degraded driving mode. Railway literature rarely addresses these topics as remote driving may lead to highly risky and complex situations. The goal of this paper is to identify how such risks can be addressed through a Human-machine cooperation approach. A first analysis has been conducted and some reflections are presented. The different steps proposed by this approach are illustrated by the use case stemming from the framework of the TC-Rail project. more...

Background Research in primary care is necessary to empower its role in health systems and improve population health. Objective The aim of this evaluation study was to assess the experiences of primary care physicians who participated as researchers in a multi-centre, mixed-methodology study on adult vaccination supported by a newly established practice-based research network. Methods Twenty-three physicians participated as researchers, operating in their own practices in 10 different prefectures of Greece. After the completion of the study, they were asked to reflect on their experiences in the research by providing written responses to the questions on the evaluation tool of the study. The open-ended questions were analyzed using thematic content analysis. Results Mean age of the researchers was 42.9 years old (±3.9, min 35, max 49) and 11 (47.8%) were male. Six themes emerged as beneficial for the participating researchers: (i) raised awareness of patients’ needs, (ii) enhancement of clinical practice and services offered, (iii) positive impact on the doctor–patient relationship, (iv) personal satisfaction, (v) enrichment of their curriculum vitae and (vi) improvement of research skills. All researchers were interested in participating in future studies. Conclusion The experience of conducting clinical research on adult vaccination in their own practices within a network was reported to be very rewarding. The benefits gained from their participation could be a valuable tool in promoting research and enhancing the quality of primary health care. more...

BACKGROUND Hemizygous mutations in GRIA3 encoding the GluA3 subunit of the amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor are known to be associated with neurodevelopmental disorders, including intellectual disability, hypotonia, an autism spectrum disorder, sleep disturbances, and epilepsy in males. OBJECTIVE To describe a new and consistent phenotype in 4 affected male patients associated with an undescribed deleterious variant in GRIA3. METHODS We evaluated a large French family in which segregate a singular phenotype according to an apparent X-linked mode of inheritance. Molecular analyses using next generation sequencing and in vitro functional studies using 2-electrode voltage clamp recordings on Xenopus laevis oocytes and a β-lactamase reporter assay in transfected human embryonic kidney (HEK293) cells were performed. RESULTS In addition to mild intellectual disability and dysarthria, affected patients presented a tightly consistent early-onset movement disorder combining an exaggerated startle reflex with generalized chorea and multifocal myoclonus. The unreported GRIA3 missense variant c.2477G > A; p.(Gly826Asp) affecting the fourth transmembrane domain of the protein was identified in index patients and their unaffected mothers. Functional studies revealed that variant receptors show decreased current response evoked by agonist (ie, kainic acid and glutamate) and reduced expression on the cell surface in favor of pathogenicity by a loss-of-function mechanism. CONCLUSIONS Taken together, our results suggest that apart from known GRIA3-related disorders, an undescribed mutation-specific singular movement disorder does exist. We thus advocate considering GRIA3 mutations in the differential diagnosis of hyperekplexia and generalized chorea with myoclonus. © 2020 International Parkinson and Movement Disorder Society. more...

International audience; Tame d0 phosphidotitanocene cations stabilized with a pendant tertiary phosphane arm are reported. These compounds were obtained by one-electron oxidation of d1 precursors with [Cp2Fe][BPh4]. The electronic structure of these compounds was studied experimentally (EPR, UV/Vis, and NMR spectroscopy, X-ray diffraction analysis) and through DFT calculations. The theoretical analysis of the bonding situation by using the electron localization function (ELF) shows the presence of π-interactions between the phosphido ligand and Ti in the d0 complexes, whereas dπ–pπ repulsion prevents such interactions in the d1 complexes. In addition, CH–π interactions were observed in several complexes, both in solution and in the solid state, between the phosphido ligand and the phosphane arm. The d0 complexes were found to be light sensitive, and decompose through Ti−P bond homolysis to give TiIII species. A naked d0 phosphidotitanocene cation has been trapped by reaction with diphenylacetylene, yielding a Ti/P frustrated Lewis pair (FLP), which was found to be less reactive than a previously reported Zr analog. more...

One of the fundamental limitations in assessing potential efficacy in Central Nervous System (CNS) transplantation of stem cells is the capacity for monitoring cell survival and migration noninvasively and longitudinally. Human glial-restricted progenitor (hGRP) cells (Q-Cells) have been investigated for their utility in providing neuroprotection following transplantation into models of amyotrophic lateral sclerosis (ALS) and have been granted a Food and Drug Administration (FDA) Investigational New Drug (IND) for intraspinal transplantation in ALS patients. Furthermore, clinical development of these cells for therapeutic use will rely on the ability to track the cells using noninvasive imaging methodologies as well as the verification that the transplanted GRPs have disease-relevant activity. As a first step in development, we investigated the use of a perfluorocarbon (PFC) dual-modal (19F magnetic resonance imaging [MRI] and fluorescence) tracer agent to label Q-Cells in culture and following spinal cord transplantation. PFCs have a number of potential benefits that make them appealing for clinical use. They are quantitative, noninvasive, biologically inert, and highly specific. In this study, we developed optimized PFC labeling protocols for Q-Cells and demonstrate that PFCs do not significantly alter the glial identity of Q-Cells. We also show that PFCs do not interfere with the capacity for differentiation into astrocytes either in vitro or following transplantation into the ventral horn of the mouse spinal cord, and can be visualized in vivo by hot spot 19F MRI. These studies provide a foundation for further preclinical development of PFCs within the context of evaluating Q-Cell transplantation in the brain and spinal cord of future ALS patients using 19F MRI. Stem Cells Translational Medicine 2019;8:355–365 more...

It has been shown that an inspiratory muscle warm-up (IMW) could enhance performance. IMW may also improve the near-infrared spectroscopy (NIRS)-derived tissue oxygen saturation index (TSI) during cycling. However, there exists contradictory data about the effect of this conditioning strategy on performance and muscle oxygenation. We examined the effect of IMW on speed skating performance and studied the underpinning physiological mechanisms related to muscle oxygenation. In a crossover, randomized, single-blind study, eight elite speed skaters performed 3000 m on-ice time trials, preceded by either IMW (2 × 30 breaths, 40% maximal inspiratory pressure) or SHAM (2 × 30 breaths, 15% maximal inspiratory pressure). Changes in TSI, oxyhemoglobin–oxymyoglobin ([O2HbMb]), deoxyhemoglobin–deoxymyoglobin ([HHbMb]), total hemoglobin–myoglobin ([THbMb]) and HHbMbdiff ([O2HbMb]–[HHbMb]) in the right vastus lateralis muscle were monitored by NIRS. All variables were compared at different time points of the race simulation with repeated-measures analysis of variance. Differences between IMW and SHAM were also analyzed using Cohen’s effect size (ES) ± 90% confidence limits, and magnitude-based inferences. Compared with SHAM, IMW had no clear impact on skating time (IMW 262.88 ± 17.62 s vs. SHAM 264.05 ± 21.12 s, effect size (ES) 0.05; 90% confidence limits, − 0.22, 0.32, p = 0.7366), TSI, HbMbdiff, [THbMb], [O2HbMb] and perceptual responses. IMW did not modify skating time during a 3000 m time trial in speed skaters, in the conditions of our study. The unchanged [THbMb] and TSI demonstrate that the mechanisms by which IMW could possibly exert an effect on performance were unaffected by this intervention. more...

Pressures on natural resources are increasing and a number of challenges need to be overcome to meet the needs of a growing population in a period of environmental variability. Some of these environmental issues can be monitored using remotely sensed Earth Observations (EO) data that are increasingly available from a number of freely and openly accessible repositories. However, the full information potential of EO data has not been yet realized. They remain still underutilized mainly because of their complexity, increasing volume, and the lack of e cient processing capabilities. EO Data Cubes (DC) are a new paradigm aiming to realize the full potential of EO data by lowering the barriers caused by these Big data challenges and providing access to large spatio-temporal data in an analysis ready form. Systematic and regular provision of Analysis Ready Data (ARD) will signi cantly reduce the burden on EO data users. Nevertheless, ARD are not commonly produced by data providers and therefore getting uniform and consistent ARD remains a challenging task. This paper presents an approach to enable rapid data access and pre-processing to generate ARD using interoperable services chains. The approach has been tested and validated generating Landsat ARD while building the Swiss Data Cube. more...

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder marked by the loss of motor neurons (MNs) in the brain and spinal cord, leading to fatally debilitating weakness. Because this disease predominantly affects MNs, we aimed to characterize the distinct expression profile of that cell type to elucidate underlying disease mechanisms and to identify novel targets that inform on MN health during ALS disease time course. microRNAs (miRNAs) are short, noncoding RNAs that can shape the expression profile of a cell and thus often exhibit cell-type-enriched expression. To determine MN-enriched miRNA expression, we used Cre recombinase-dependent miRNA tagging and affinity purification in mice. By defining thein vivomiRNA expression of MNs, all neurons, astrocytes, and microglia, we then focused on MN-enriched miRNAs via a comparative analysis and found that they may functionally distinguish MNs postnatally from other spinal neurons. Characterizing the levels of the MN-enriched miRNAs in CSF harvested from ALS models of MN disease demonstrated that one miRNA (miR-218) tracked with MN loss and was responsive to an ALS therapy in rodent models. Therefore, we have used cellular expression profiling tools to define the distinct miRNA expression of MNs, which is likely to enrich future studies of MN disease. This approach enabled the development of a novel, drug-responsive marker of MN disease in ALS rodents.SIGNIFICANCE STATEMENTAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disease in which motor neurons (MNs) in the brain and spinal cord are selectively lost. To develop tools to aid in our understanding of the distinct expression profiles of MNs and, ultimately, to monitor MN disease progression, we identified small regulatory microRNAs (miRNAs) that were highly enriched or exclusive in MNs. The signal for one of these MN-enriched miRNAs is detectable in spinal tap biofluid from an ALS rat model, where its levels change as disease progresses, suggesting that it may be a clinically useful marker of disease status. Furthermore, rats treated with ALS therapy have restored expression of this MN RNA marker, making it an MN-specific and drug-responsive marker for ALS rodents. more...

Connexin 43 (Cx43) gap junctions and hemichannels mediate astrocyte intercellular communication in the central nervous system under normal conditions and may contribute to astrocyte-mediated neurotoxicity in amyotrophic lateral sclerosis (ALS). Here we show that astrocyte-specific knockout of Cx43 in a mouse model of ALS slows disease progression both spatially and temporally, provides motor neuron (MN) protection, and improves survival. In human ALS tissues and biofluids, we observe that higher levels of Cx43 correlate with accelerated disease progression. Using human iPSC-derived astrocytes (hiPSC-A) from both familial and sporadic ALS, we show that Cx43 is upregulated and that Cx43-hemichannels are enriched at the astrocyte membrane. We then demonstrate that the pharmacological blockade of Cx43-hemichannels in ALS astrocytes, during a specific temporal window, provides neuroprotection of hiPSC-MN and reduces ALS astrocyte-mediated neuronal hyperexcitability. Our data identify Cx43 hemichannels as novel conduits of astrocyte-mediated disease progression and a pharmacological target for disease-modifying ALS therapies. more...

When working on intelligent tutor systems designed for mathematics education and its specificities, an interesting objective is to provide relevant help to the students by anticipating their next steps. This can only be done by knowing, beforehand, the possible ways to solve a problem. Hence the need for an automated theorem prover that provide proofs as they would be written by a student. To achieve this objective, logic programming is a natural tool due to the similarity of its reasoning with a mathematical proof by inference. In this paper, we present the core ideas we used to implement such a prover, from its encoding in Prolog to the generation of the complete set of proofs. However, when dealing with educational aspects, there are many challenges to overcome. We also present the main issues we encountered, as well as the chosen solutions., Comment: In Proceedings ThEdu'19, arXiv:2002.11895 more...

Aims. This study aims to (i) translate, culturally adapt, and validate the Jefferson Scale of Patient Perception of Physician Empathy questionnaire for the Greek population (Gr-JSPPPE) and (ii) estimate physicians’ self-assessed empathy and patients’ perceptions of physicians’ empathy, investigate their relationship, and assess their predictors.Methods. A total of 189 patients and 17 physicians from an internal medicine clinic took part in the study. A composite questionnaire was administered to the patients, consisting of (1) sociodemographic items, (2) hospitalization-related questions, (3) the Zung Self-Rating Anxiety Scale, (4) the Patient Health Questionnaire (PHQ-9), (5) the EQ-5D-5L Questionnaire, (6) the Gr-JSPPPE, and (7) the Visual Analog Scale for pain. The physicians’ composite questionnaire comprised (1) sociodemographic items, (2) the EQ-5D-5L questionnaire, and (3) the Toronto Composite Empathy Scale (TCES). Exploratory and confirmatory factor analyses were conducted to assess the psychometric properties of the Gr-JS PPPE. Univariate comparisons were performed between (a) empathy measures and (b) sociodemographic and health-related measures of both groups; multivariate regression analysis for the Gr-JSPPPE adjusting for baseline confounders was executed.Results. Statistically significant negative correlations were found between the Gr-JSPPPE mean score and the TCES personal/cognitive, professional/cognitive, and professional/emotional subscales. Female sex, being married, duration of employment in current post, and physicians’ EQ-5D index score emerged as important predictors of increased physician empathy. Patients’ EQ-VAS “thermometer” scale was significantly associated with the Gr-JSPPPE total score at the multivariate level.Conclusion. The Gr-JSPPPE is a psychometrically sound tool to assess patient perceptions of physician empathy. Physician empathy assessed by the self-reported scale is inversely associated with patient perceptions. more...

A blocking state is a measurable state on an intelligent tutoring systems’ user interface, which mirrors a student’s cognitive state where she/he cannot temporarily make any progress toward finding a solution to a problem. In this paper, we present the development of four probabilistic models to detect a blocking state of students while they are solving a Canadian high school-level problem in Euclidean geometry on an ITS. Our methodology includes experimentation with a modified version of QED-Tutrix, an ITS, which we used to gather labelled datasets composed of sequences of mouse and keyboard actions. We developed four predicting models: an action-frequency model, a subsequence-detection model, a 1D convolutional neural network model and a hybrid model. The hybrid model outperforms the others with a \(F_1\) score of 80.4% on the classification of blocking state on validation set while performing 77.3% on the test set. more...

International audience; Herein we report the synthesis of new ditopic ligands, which consist of a phenoxy group and N,N,N'trisubstituted amidines linked by a methylene spacer (L1-L4). Their coordination chemistry has been studied/investigated with Zn(II) and Al(III). Alkane elimination route between the phenol-amidine proligands (L1H-L4H) and Et2Zn led to dinuclear complexes [(L1-L4)ZnEt]2 (1a-4a) in which the Zn centers are chelated by phenoxyamidine ligands and bridged through the oxygen atom of the phenoxy groups. Salt metathesis reaction between two equivalents of the sodium amidine phenate L1Na and ZnCl2 led to a bis-chelate chiral spiro-complex (L12Zn) 1a'. Analogous alkane elimination route between AlMe3 and the phenol-amidine proligands L1H-L4H allowed the preparation of the mononuclear complexes [(L1-L4)AlMe2] (1b-4b). The phenoxyamidine-Al and Zn complexes have been characterized by NMR spectroscopy, elemental analysis and/or high resolution ESI-MS. The solid state structures of the proligands [L1H2][Br] and L2H as well as of six complexes have been established by single crystal X-ray diffraction analysis. Fluxional properties of the proligands L1H-L2H and of the complexes 1a and 2b have been investigated by VT NMR experiments. In the presence of an alcohol source, complexes 1a-4a and 1b-4b were used as initiators for the controlled ring-opening polymerization (ROP) of rac-lactide to afford atactic polylactic acid (PLA). more...

Introduction: Discovery of pulmonary nodule is a frequent situation. In order to obtain the pathological diagnosis of a peripheral lesion with a chest wall contact, ultrasound-guided lung biopsy appears to be a valuable tool for the pulmonologist. Objectives of Our Study: Defining yield and complication rates of ultrasound-guided lung biopsies performed by pulmonologists. Methods: We performedthe first french multi-centric prospective study during a period of 8 months between July 2017 and February 2018 and were compiled to assess procedure characteristics and results. All of the procedures were performed by pulmonologists. Results: A total of 62 procedures were collected in 5 French centers. Diagnosis was established in 85,5% of cases which were mostly neoplasia (82,3%). Presence of chest wall structures invasion was associated with a diagnosis obtaining (p = 0,01). 9 complications were found (15% of all procedures) without any need of higher level of care. A chest wall contact length Conclusion: Our study confirms an excellent diagnostic reliability with a low complication rate of ultrasound-guided lung biopsy performed by pulmonologists while providing patients comfort. This technic deserves a generalization in pulmonology wards, it is easy to put in place and seems fast to learn. more...

Cet article est un compte-rendu du livre : Marie‑Christine Gomez‑Géraud & Jean‑René Valette (dir.), Le Discours mystique entre Moyen Âge et première modernité, t. 1, La question du langage, Paris, Honoré Champion, coll. « Mystica », 2019, 578 p., EAN 9782745349644. more...

Cet article est un compte-rendu du livre : Michel Collot, Le Chant du monde dans la poésie française contemporaine, Paris : José Corti, coll. « Les Essais », 2019, 360 p., EAN 9782714312174.

Cet article est un compte-rendu du livre : Proust et Alain-Fournier. La transgression des genres. 1913-1914, sous la direction de Mireille Naturel, Paris : Honoré Champion, coll. « Recherches proustiennes », 2017, 252 p., EAN 9782745331748. more...

The redefinition of the kilogram, expected to be approved in the autumn of 2018, will replace the artefact definition of the kilogram by assigning a fixed numerical value to a fundamental constant of physics. While the concept of such a change is pleasing, the mass community as represented by the Consultative Committee for Mass and Related Quantities (CCM) was faced with a number of technical and procedural challenges that needed to be met in order to profit in any meaningful way from the proposed change. In the following, we outline these challenges and how the CCM has met and is meeting them. We focus especially on what the mass community requires of the new definition and the process by which the CCM has sought to ensure that these needs will be met. more...

Our article aims to show how illuminating mathematical work as a concept from didactics of mathematics is useful in understanding issues relating to proving and learning of proof, with or without technology. After posing our hypotheses on the relationship of proof with mathematical work, the pedagogical intent of historical elements of geometry and the use of modern technical tools, we present reference contexts and situations around the property of the tangent. These contexts and situations allow for a comparison of the validation modes, the type of epistemic necessity at stake and certain underlying discourse peculiarities. We introduce the idea of a “valence of mathematical work” and we interpret in an a priori approach the main interactions that could maintain a model user-reader in a mathematical working space. We pay special attention to an extract of Elemens de Geometrie by Alexis Claude Clairaut, with one of the reference contexts revisiting his problem with the assistance of dynamic geometry software. more...

SummaryDuchenne muscular dystrophy (DMD) remains an intractable genetic disease. Althogh there are several animal models of DMD, there is no human cell model that carries patient-specific DYSTROPHIN mutations. Here, we present a human DMD model using human induced pluripotent stem cells (hiPSCs). Our model reveals concordant disease-related phenotypes with patient-dependent variation, which are partially reversed by genetic and pharmacological approaches. Our “chemical-compound-based” strategy successfully directs hiPSCs into expandable myoblasts, which exhibit a myogenic transcriptional program, forming striated contractile myofibers and participating in muscle regeneration in vivo. DMD-hiPSC-derived myoblasts show disease-related phenotypes with patient-to-patient variability, including aberrant expression of inflammation or immune-response genes and collagens, increased BMP/TGFβ signaling, and reduced fusion competence. Furthermore, by genetic correction and pharmacological “dual-SMAD” inhibition, the DMD-hiPSC-derived myoblasts and genetically corrected isogenic myoblasts form “rescued” multi-nucleated myotubes. In conclusion, our findings demonstrate the feasibility of establishing a human “DMD-in-a-dish” model using hiPSC-based disease modeling. more...

The efficacy of drugs targeting the CNS is influenced by their limited brain access, which can lead to complete pharmacoresistance. Recently a tissue-specific and selective upregulation of the multidrug efflux transporter ABCB1 or P-glycoprotein (P-gp) in the spinal cord of both patients and the mutant SOD1-G93A mouse model of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease that prevalently kills motor neurons has been reported. Here, we extended the analysis of P-gp expression in the SOD1-G93A ALS mouse model and found that P-gp upregulation was restricted to endothelial cells of the capillaries, while P-gp expression was not detected in other cells of the spinal cord parenchyma such as astrocytes, oligodendrocytes, and neurons. Using both in vitro human and mouse models of the blood-brain barrier (BBB), we found that mutant SOD1 astrocytes were driving P-gp upregulation in endothelial cells. In addition, a significant increase in reactive oxygen species production, Nrf2 and NFκB activation in endothelial cells exposed to mutant SOD1 astrocytes in both human and murine BBB models were observed. Most interestingly, astrocytes expressing FUS-H517Q, a different familial ALS-linked mutated gene, also drove NFκB-dependent upregulation of P-gp. However, the pathway was not dependent on oxidative stress but rather involved TNF-α release. Overall, these findings indicated that nuclear translocation of NFκB was a converging mechanism used by endothelial cells of the BBB to upregulate P-gp expression in mutant SOD1-linked ALS and possibly other forms of familial ALS. GLIA 2016 GLIA 2016;64:1298-1313. more...

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive loss of motor neurons in the CNS. Astrocytes play a critical role in disease progression of ALS. Astrocytes are interconnected through a family of gap junction proteins known as connexins (Cx). Cx43 is a major astrocyte connexin conducting crucial homeostatic functions in the CNS. Under pathological conditions, connexin expression and functions are altered. Here we report that an abnormal increase in Cx43 expression serves as one of the mechanisms for astrocyte-mediated toxicity in ALS. We observed a progressive increase in Cx43 expression in the SOD1(G93A) mouse model of ALS during the disease course. Notably, this increase in Cx43 was also detected in the motor cortex and spinal cord of ALS patients. Astrocytes isolated from SOD1(G93A) mice as well as human induced pluripotent stem cell (iPSC)-derived astrocytes showed an increase in Cx43 protein, which was found to be an endogenous phenomenon independent of neuronal co-culture. Increased Cx43 expression led to important functional consequences when tested in SOD1(G93A) astrocytes when compared to control astrocytes over-expressing wild-type SOD1 (SOD1(WT) ). We observed SOD1(G93A) astrocytes exhibited enhanced gap junction coupling, increased hemichannel-mediated activity, and elevated intracellular calcium levels. Finally, we tested the impact of increased expression of Cx43 on MN survival and observed that use of both a pan Cx43 blocker and Cx43 hemichannel blocker conferred neuroprotection to MNs cultured with SOD1(G93A) astrocytes. These novel findings show a previously unrecognized role of Cx43 in ALS-related motor neuron loss. GLIA 2016;64:1154-1169. more...

Lorsque Ricœur pense l’histoire, il fait de l’ecriture (ou du temoignage) cette necessaire ressaisie de l’evenement qui fait acceder le passe au rang de sur objet. Lorsque Peguy medite l’histoire, il fait du saisissement (ou de l’apparition) ce necessaire climat de la memoire qui laisse exister l’avenement comme singularite meme du reel. On propose ici un retour a la phenomenologie de Peguy, par-dela l’hermeneutique de Ricœur, afin que l’histoire de l’art ne risque plus de se substituer a la rencontre de l’art en nos esprits modernes, tant il semble vrai qu’expliquer toute singularite artistique par la genealogie de faits, de documents et d’influences nous repousserait sans doute dangereusement en plein positivisme. more...

Pressures on natural resources are increasing and a number of challenges need to be overcome to meet the needs of a growing population in a period of environmental variability. The key to sustainable development is achieving a balance between the exploitation of natural resources for socioeconomic development and maintaining ecosystem services that are critical to human’s wellbeing and livelihoods. Some of these environmental issues can be monitored using remotely sensed Earth Observations (EO) data that are increasingly available from freely and openly accessible repositories. Hereafter, we present the Swiss Data Cube, a unique Analysis Ready Data archive of satellite imagery and some use cases to monitor Sustainable Development Goals. more...

Our article aims to define the notion of instrumental proof based on didactic, epistemological and cognitive considerations. We raise issues and challenges related to the use of this type of proof in mathematical work and mathematical thinking. The theory of mathematical working spaces serves as a construct on which we address questions about proof, reasoning and epistemic necessity, taking advantage of the possibilities offered by the development geneses and fibrations in an instrumented perspective. The coordination of the semiotic, discursive and instrumental geneses of the working space founds discursive-graphic proofs, mechanical proofs and algorithmic proofs that are activated at school in the subject-milieu interactions. We end with a discussion on some consequences of the computer-assisted modelling of the learning conditions of mathematics, and we conclude on a necessary reconciliation of heuristics and validation. more...

Cet article est un compte-rendu du livre : Juliette Carré, Correspondances d’Alain-Fournier, Jacques Rivière et André Lhote. Une École des Lettres à la Belle Époque, Paris : Honoré Champion, coll. « littérature de notre siècle », 2018, 426 p., EAN 9782745346377. more...

Cet article est un compte-rendu du livre : Agnès Lachaume, Le Langage du désir chez Bossuet. Chercher quelque ombre d’infinité, Paris : Honoré Champion, coll. « Lumière classique », 2017, 732 pages, EAN 9782745331762. more...

The management of patients with high cardiovascular risk and OSA must target not only improving adherence to CPAP, but should also include strategies aimed at reducing BP and increasing physical activity. The study aims to evaluate the effectiveness of an integrated intervention using remote patient telemonitoring in reducing BP in high cardiovascular risk patients with OSA.In a multicenter, open, randomized trial, patients with OSA were randomly assigned at CPAP initiation to usual care or multimodal telemonitoring for 6 months. Telemonitoring used electronic equipment collecting information about BP, symptoms, CPAP side effects, and physical activity with home care providers prespecified protocoled actions. The primary effectiveness outcome was assessed using home self-measured BP on 3 consecutive days. Secondary outcomes included CPAP compliance, symptoms, and physical activity.Of 306 patients with a median age of 61.3 years [interquartile range, 54.1; 66.1], who were predominantly men, 226 (74%) with a BMI of 32.0 [28.7; 35.6] kg/mIn OSA patients with high cardiovascular risk, multimodal telemonitoring was not superior to usual CPAP care for improving home BP; however, telemonitoring improved adherence and patient-centered outcomes. more...

Three new gold(I)-coumarin-based trackable therapeutic complexes and two non-trackable analogues have been synthesised and fully characterised. They all display anti-proliferative properties on several types of cancer cell lines, including those of colon, breast, and prostate. Two complexes displayed significant anti-inflammatory effects; one displayed pro-inflammatory behaviour; this highlights the impact of the position of the fluorophore on the caffeine scaffold. Additionally, the three coumarin derivatives could be visualised in vitro by two-photon microscopy. more...

We recently demonstrated that microRNA-218 (miR-218) is greatly enriched in motor neurons and is released extracellularly in amyotrophic lateral sclerosis model rats. To determine if the released, motor neuron-derived miR-218 may have a functional role in amyotrophic lateral sclerosis, we examined the effect of miR-218 on neighbouring astrocytes. Surprisingly, we found that extracellular, motor neuron-derived miR-218 can be taken up by astrocytes and is sufficient to downregulate an important glutamate transporter in astrocytes [excitatory amino acid transporter 2 (EAAT2)]. The effect of miR-218 on astrocytes extends beyond EAAT2 since miR-218 binding sites are enriched in mRNAs translationally downregulated in amyotrophic lateral sclerosis astrocytes. Inhibiting miR-218 with antisense oligonucleotides in amyotrophic lateral sclerosis model mice mitigates the loss of EAAT2 and other miR-218-mediated changes, providing an important in vivo demonstration of the relevance of microRNA-mediated communication between neurons and astrocytes. These data define a novel mechanism in neurodegeneration whereby microRNAs derived from dying neurons can directly modify the glial phenotype and cause astrocyte dysfunction. more...

Cet article est un compte-rendu du livre : Éva Martin, Esthétiques de Port-Royal, Paris, Classiques Garnier, coll. « Univers Port‑Royal » n° 32, 2018, 620 pages, EAN : 9782406069584.

Purpose: Nitrate supplementation can increase tolerance to high-intensity work rates; however, limited data exist on the recovery of performance. The authors tested whether 5 d of nitrate supplementation could improve repeated time-trial performance in speed skating. Methods: Using a double-blind, placebo-controlled, crossover design, 9 international-level short-track speed skaters ingested 1 high (juice blend, ∼6.5 mmol nitrate; HI) or low dose (juice blend, ∼1 mmol nitrate; LO) per day on days 1–4. After a double dose of either HI or LO on day 5, athletes performed 2 on-ice 1000-m time trials, separated by 35 min, to simulate competition races. Differences between HI and LO were compared with the smallest practically important difference. Results: Salivary [nitrate] and [nitrite] were higher in HI than LO before the first (nitrate: 81%, effect size [ES]: 1.76; nitrite: 72%, ES: 1.73) and second pursuits (nitrate: 81%, ES: 1.92; nitrite: 71%, ES: 1.78). However, there was no difference in performance in the first (LO: 90.92 [4.08] s; HI: 90.95 [4.06] s, ES: 0.01) or the second time trial (LO: 91.16 [4.06] s; HI: 91.55 [4.40] s, ES: 0.09). Plasma [lactate] measured after the trials (LO: 14.8 [1.1] mM; HI: 14.8 [1.2] mM, ES: 0.01) and at the end of the recovery period (LO: 9.8 [2.1] mM; HI: 10.2 [1.9] mM, ES: 0.05) was not different between treatments. Conclusion: Five days of high-dose nitrate supplementation did not change physiological responses and failed to improve single and repeated time-trial performances in world-class short-track speed skaters. These data suggest that nitrate ingestion up to 6.5 mmol does not enhance recovery from supramaximal exercise in world-class athletes. more...

This chapter provides a comprehensive view of the research in geometry education that has been presented during Congress of European Research in Mathematics Education (CERME) conferences. It focuses on the close link between theoretical and empirical aspects that has always guided the researchers of the group. The chapter discusses some methodological and theoretical tools developed within the group are introduced and shows how the constituted a common support for studies in the field. It focuses on the main findings from the group are given by emphasising the spirit of communication and collaboration built up through the different meetings. The chapter traces a common research agenda is considered that could be organised to achieve a deeper understanding of geometrical thinking and competencies through the whole education. Geometry is traditionally viewed as a work on geometrical configurations which are both tangible signs and abstract mathematical objects. more...