PICARD Fabienne

The main objective of this PhD thesis is to define and study the process of co-construction of the social acceptability of hydrogen, as well as the stakes it represents for the energy transition in the territories. For this purpose, two study areas have been selected, each of which includes a hydrogen mobility demonstration project: Navibus H2 (Nantes) and HyWay (Lyon). As a comparison, the results of a study carried out before the thesis on a third field, GRHYD (Urban Community of Dunkerque) were also integrated into this thesis. The methodology, using various theoretical concepts, was designed to take into account the fact that the subject of the study is not well known by the general public. Surveys were carried out by questionnaire and interviews: in Nantes, before the demonstration, with users of an electric river shuttle and actors of the district served by this shuttle, and in Lyon, during the demonstration, with users of hydrogen-powered electric vehicles, as well as with officials and elected representatives of the metropolis. The results are then analyzed using statistical and textual analyses, and compared with each other and with those of the preliminary survey carried out in Dunkirk. It was thus possible to highlight a set of representations, expectations or attitudes related to hydrogen and more or less shared between the groups studied. A reflection is then proposed on the way to consider a study of social acceptability in connection with demonstration projects, as well as the assets that this represents for an energy transition in the territories.

The objective of this paper is to study the supply side of the silver market, which is usually neglected by research on this topic. Adopting a systemic approach to innovation, our main goals are to identify the nature of the innovations developed, the way innovations are created, and the issues related to their emergence and diffusion. Our research is based on an empirical study of the French silver economy, which consists in an enquiry carried out in Silver Valley. The results of our study lead us to suggest a new term ‘geront’innovation’ to qualify the various forms of innovations developed to cater for the needs of elderly people. We also put forward the importance of networking and open innovation strategies. Finally, the identified barriers to emergence and diffusion as perceived by the supply side of the market lead us to suggest recommendations to support the diffusion of geront’innovations.

The forage feed value determined by organic matter digestibility (OMD) and voluntary intake (VI) is hard and expensive. Thus, several indirect methods such as near infrared reflectance (NIR) spectroscopy have been developed for predicting the feed value of forages. In this study, NIR spectra of 1040 samples of feces from sheep fed fresh temperate forages were used to develop calibration models for the prediction of fecal crude ash (CA), fecal crude protein (CP), fresh forage OMD, and VI. Another 136 samples of feces were used to assess these models. Four calibration strategies were compared: (1) species-specific calibration. (2) family-specific calibration. (3) a global procedure. and (4) a LOCAL approach. The first three strategies were based on classical regression models developed on different sample populations, whereas the LOCAL approach is based on the development models from selected samples spectrally similar to the sample to be predicted. The first two strategies use feces-samples grouping based on the species or the family of the forage ingested. Forage calibration data sets gave value ranges of 79-327g/kg dry matter (DM) for CA, 65-243g/kg DM for CP, 0.52-0.85g/g for OMD, and 34.7-100.5g DM/kg metabolic body weight (BW0.75) for VI. The prediction of CA and CP content in feces by species-specific fecal NIR (FNIR) spectroscopy models showed lower standard error of prediction (SEP) (CA 15.03 and CP 7.48g/kg DM) than family-specific (CA 21.93 and CP 7.69g/kg DM), global (CA 19.83 and CP 7.98g/kg DM), or LOCAL (CA 30.85 and CP 8.10g/kg DM) models. For OMD, the LOCAL procedure led to a lower SEP (0.018g/g) than the other approaches (0.023, 0.024, and 0.023g/g for species-specific, family-specific, and global models, respectively). For VI, the LOCAL approach again led to a lower SEP (6.15g/kg BW0.75) than the other approaches (7.35, 8.00, and 8.13g/kg BW0.75 for the species-specific, family-specific, and global models, respectively). LOCAL approach performed on FNIR spectroscopy samples gives more precise models for predicting OMD and VI than species-specific, family-specific, or global approaches.

The pharmaceutical industry requires narrow variability in the dissolution rate of hard gelatin capsules. To test this property, gelatin is aged in high temperature and humidity conditions to mimic gelatin shelf-life. These conditions induce cross-link formation in gelatin chains and change the properties of the capsule. Gelatin is produced worldwide in various environmental conditions. This study set out to evaluate the impact of geographic production origin on gelatin composition, before and after aging treatment, and on its dissolution properties. Non-aged and aged pig skin gelatins from three different production plants (A, B and C) were analyzed in raw granules and in powder by near infrared and fluorescence spectroscopy to identify the mechanisms of cross-link formation during aging. Gelatin composition (lipids, dityrosine, 3,4 dihydroxyphenylalanine (DOPA)) and oxidation level, before and after aging, varied according to production origin. The gelatin from C showed no variability in dissolution rate, while gelatins from A and B dissolved more slowly after aging. Near infrared spectroscopy results suggest that water was more strongly bound to the gelatin chains in the gelatins that yielded non-compliant dissolution test results. Non-compliant gelatin exhibited more CH2, usually assigned to lipids, and more aldehydes. Even before aging we found that non-compliant gelatins tended to fluoresce more at 344 nm under 280 nm excitation. These results open new perspectives for designing tools to predict the dissolution quality of freshly produced gelatins.

The adoption of the law on the energy transition for green growth and the holding of the XXIst edition of the UN Climate Conference testify to an individual and collective awareness of the impacts of human activity on the environment. This book deals with the implementation of structural transformations - the transition - that allow for the emergence of environmentally friendly socio-technical systems. The hypothesis is that the structural change of a society is analyzed through technological, societal and institutional innovations. The question of sustainable transition is studied through the analysis of two vital functions: energy and agriculture/agri-food. Innovation and Techno-Ecological Transition invites the reader to question the "classic" models of innovation and to observe the processes and blocking factors that constitute obstacles to the success of the transition.

Objective The discovery of mutations in DEPDC5 in familial focal epilepsies has introduced a novel pathomechanism to a field so far dominated by ion channelopathies. DEPDC5 is part of a complex named GAP activity toward RAGs (GATOR) complex 1 (GATOR1), together with the proteins NPRL2 and NPRL3, and acts to inhibit the mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) pathway. GATOR1 is in turn inhibited by the GATOR2 complex. The mTORC1 pathway is a major signaling cascade regulating cell growth, proliferation, and migration. We aimed to study the contribution of GATOR complex genes to the etiology of focal epilepsies and to describe the associated phenotypical spectrum. Methods We performed targeted sequencing of the genes encoding the components of the GATOR1 (DEPDC5, NPRL2, and NPRL3) and GATOR2 (MIOS, SEC13, SEH1L, WDR24, and WDR59) complex in 93 European probands with focal epilepsy with or without focal cortical dysplasia. Phospho-S6 immunoreactivity was used as evidence of mTORC1 pathway activation in resected brain tissue of patients carrying pathogenic variants. Results We identified four pathogenic variants in DEPDC5, two in NPRL2, and one in NPRL3. We showed hyperactivation of the mTORC1 pathway in brain tissue from patients with NPRL2 and NPRL3 mutations. Collectively, inactivating mutations in GATOR1 complex genes explained 11% of cases of focal epilepsy, whereas no pathogenic mutations were found in GATOR2 complex genes. GATOR1-related focal epilepsies differ clinically from focal epilepsies due to mutations in ion channel genes by their association with focal cortical dysplasia and seizures emerging from variable foci, and might confer an increased risk of sudden unexplained death in epilepsy (SUDEP). Significance GATOR1 complex gene mutations leading to mTORC1 pathway upregulation is an important cause of focal epilepsy with cortical malformations and represents a potential target for novel therapeutic approaches.

Predicting forage feed value is a vital part of estimating ruminant performances. Most near-infrared (NIR) reflectance calibration models have been developed on oven-dried green forages, but preserved forages such as hays or silages are a significant part of real-world farm practice. Fresh and preserved forages give largely similar fodder, but drying or ensiling processes could modify preserved forage spectra which would make the oven-dried green forage model unsuitable to use on preserved forage samples. The aim of this study was to monitor the performance of oven-dried green forage calibration models on a set of hay and silage to predict their nutritive value. Local and global approaches were tested and 1025 green permanent grassland forages, 46 types of hay, and 27 types of silage were used. The samples were scanned by NIR spectroscopy and analyzed for nitrogen, neutral detergent fiber, acid detergent fiber, and pepsin-cellulase dry matter digestibility (PCDMD). Local and global calibrations were developed on 975 oven-dried green forage spectra and tested on 50 samples of oven-dried green forages, 46 samples of hay, and 27 samples of silage. For oven-dried green forage and hay validation sets, Mahalanobis distance (H) between these samples and the calibration population center was lower than 3. No significant standard error of prediction differences was obtained when calibration models were applied to oven-dried green forage and hay validation sets. For silage, the H-distance was higher than 3, meaning that calibration models built from oven-dried green forages cannot be applied to silage samples. We conclude that local calibration outperforms global strategy on predicting the PCDMD of oven-dried green forages and hay.

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The Revolution of 1789 profoundly modified the art of governing the State. Public law should no longer serve to reinforce the power of the sovereign over his subjects. If its ambition was to promote and facilitate the development of commercial exchanges, it also proposed to justify to the citizens the validity of the ownership of capital by the bourgeoisie, as well as the legitimacy of this new State. To achieve these two objectives, violence alone, of which the state theoretically has a monopoly, would not suffice. The revolutionaries of Jacobin inspiration thus envisage an administrative reform of the Nation, which must prove to be simple, inexpensive and especially readable for the citizen. Two tendencies of territorial organization emerged: one was centralized and authoritarian, which regularly led to failures, the other preferred to stimulate local initiatives and to obtain better results. The Pays de Montbéliard, which was already one of the strongholds of the Industrial Revolution, was one of the forerunners of this second trend through the creation, as early as 1959, of an urban district, the DUPM. Under the presidency of André Boulloche, this new institution anticipated the decentralization laws almost two decades in advance by positioning itself as a counter-power, on the one hand to a State still considered very centralizing and authoritarian, and on the other hand to the car manufacturer Peugeot, whose development after the Second World War generated a prosperous but fragile situation of mono-industry. However, this very political vision did not last when the fight against unemployment became a vital issue in the 1980s. At the same time, the laws of decentralization, and then European construction, imposed an increasingly framed legal environment that seemed to diminish this anticipatory vision and tended, with local authorities, to favor increasingly wait-and-see and technical postures.

The pharmaceutical industry requires a narrow variability in gelatin properties during storage to meet strict quality standards for hard capsules. To test the properties of gelatin during shelf life, gelatin is aged in high temperature and high humidity conditions. These conditions induce the formation of cross-links in gelatin chains that impact its chemical composition and thereby the properties of the capsules. Non-aged and aged pig skin gelatins were analyzed in raw granule or powder forms by near-infrared and fluorescence spectroscopy to elucidate the mechanisms of cross-link formation during aging. Both near-infrared and fluorescence spectroscopy clearly separated non-aged from aged samples. Aging induced the formation of dityrosine and other cross-links involving amine and aldehyde functions. The presence of 3,4-dihydroxyphenylalanine (DOPA), a fluorescent product of tyrosine oxidation involved in cross-link formation, was evidenced in gelatin.

This book aims to present a systemic perspective on the techno-ecologic transition to a decarbonated society. The transition towards a low-carbon society is currently an important political, technological, economical and social issue. This transition implies a paradigmatic shift in energy production and energy consumption, in human interaction with natural resources. It questions the way of developing more sustainable technologies and the role of innovations in this process, whether technological or not. How do we go beyond the current lock-in generated by fossil energy? The ongoing progress of innovation is analyzed in the context of a number of the main societal functions, with a focus on energy and food production. However, there remains a gap between intention and action and the management of this transition will take time and will require a broad diffusion of knowledge about this topic among the relevant economic, legal and political actors. The purpose of this book is to highlight from a systemic perspective what is at stake in the current innovations.

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Regions build their economic advantage on their ability to mobilize and channel knowledge. The challenge of this research is to understand the dynamics at work in the inter-actor relations that explain the underperformance of some or the creative capacities of others through the diffusion of knowledge or learning. The challenge is to identify how individuals, firms and institutions interact and the effects of their interaction on regional innovation performance. We propose to approach this topic of study from the perspective of convention theory, exploring other important dimensions of creativity and learning, particularly by articulating the notions of trust and belief. Individuals act and interact in a social context governed by conventions. Action cannot take place without the existence of a number of conventions. A major problem with conventions is that they often limit the set of possible actions. They structure and constrain the action. They are not unrelated to the notions of trust and belief in question.

Epilepsy is both a disease of the brain and the mind. Here, we present the first of two papers with extended summaries of selected presentations of the Third International Congress on Epilepsy, Brain and Mind (April 3-5, 2014. Brno, Czech Republic). Epilepsy in history and the arts and its relationships with religion were discussed, as were overviews of epilepsy and relevant aspects of social cognition, handedness, accelerated forgetting and autobiographical amnesia, and large-scale brain networks.

Objective The DEPDC5 (DEP domain-containing protein 5) gene, encoding a repressor of the mTORC1 signaling pathway, has recently emerged as a major gene mutated in familial focal epilepsies. We aimed to further extend the role of DEPDC5 to focal cortical dysplasias (FCDs). Methods Seven patients from 4 families with DEPDC5 mutations and focal epilepsy associated with FCD were recruited and investigated at the clinical, neuroimaging, and histopathological levels. The DEPDC5 gene was sequenced from genomic blood and brain DNA. Results All patients had drug-resistant focal epilepsy, 5 of them underwent surgery, and 1 had a brain biopsy. Electroclinical phenotypes were compatible with FCD II, although magnetic resonance imaging (MRI) was typical in only 4 cases. Histopathology confirmed FCD IIa in 2 patients (including 1 MRI-negative case) and showed FCD I in 2 other patients, and remained inconclusive in the last 2 patients. Three patients were seizure-free postsurgically, and 1 had a worthwhile improvement. Sequencing of blood DNA revealed truncating DEPDC5 mutations in all 4 families. 1 mutation was found to be mosaic in an asymptomatic father. A brain somatic DEPDC5 mutation was identified in 1 patient in addition to the germline mutation. Interpretation Germline, germline mosaic, and brain somatic DEPDC5 mutations may cause epilepsy associated with FCD, reinforcing the link between mTORC1 pathway and FCDs. Similarly to other mTORopathies, a “2-hit” mutational model could be responsible for cortical lesions. Our study also indicates that epilepsy surgery is a valuable alternative in the treatment of drug-resistant DEPDC5-positive focal epilepsies, even if the MRI is unremarkable.

Objective: To identify the genetic cause in a large family with febrile seizures (FS) and temporal lobe epilepsy (TLE) and subsequently search for additional mutations in a cohort of 107 families with FS, with or without epilepsy. Methods: The cohort consisted of 1 large family with FS and TLE, 64 smaller French families recruited through a national French campaign, and 43 Italian families. Molecular analyses consisted of whole-exome sequencing and mutational screening. Results: Exome sequencing revealed a p.Glu402fs*3 mutation in the γ2 subunit of the GABAA receptor gene (GABRG2) in the large family with FS and TLE. Three additional nonsense and frameshift GABRG2 mutations (p.Arg136*, p.Val462fs*33, and p.

The neural mechanisms that underlie consciousness are not fully understood. We describe a region in the human brain where electrical stimulation reproducibly disrupted consciousness. A 54-year-old woman with intractable epilepsy underwent depth electrode implantation and electrical stimulation mapping. The electrode whose stimulation disrupted consciousness was between the left claustrum and anterior-dorsal insula. Stimulation of electrodes within 5mm did not affect consciousness. We studied the interdependencies among depth recording signals as a function of time by nonlinear regression analysis (h(2) coefficient) during stimulations that altered consciousness and stimulations of the same electrode at lower current intensities that were asymptomatic. Stimulation of the claustral electrode reproducibly resulted in a complete arrest of volitional behavior, unresponsiveness, and amnesia without negative motor symptoms or mere aphasia. The disruption of consciousness did not outlast the stimulation and occurred without any epileptiform discharges. We found a significant increase in correlation for interactions affecting medial parietal and posterior frontal channels during stimulations that disrupted consciousness compared with those that did not. Our findings suggest that the left claustrum/anterior insula is an important part of a network that subserves consciousness and that disruption of consciousness is related to increased EEG signal synchrony within frontal-parietal networks.

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The main familial focal epilepsies are autosomal dominant nocturnal frontal lobe epilepsy, familial temporal lobe epilepsy and familial focal epilepsy with variable foci. A frameshift mutation in the DEPDC5 gene (encoding DEP domain-containing protein 5) was identified in a family with focal epilepsy with variable foci by linkage analysis and exome sequencing. Subsequent pyrosequencing of DEPDC5 in a cohort of 15 additional families with focal epilepsies identified 4 nonsense mutations and 1 missense mutation. Our findings provided evidence of frequent (37%) loss-of-function mutations in DEPDC5 associated with a broad spectrum of focal epilepsies. The implication of a DEP (Dishevelled, Egl-10 and Pleckstrin) domain-containing protein that may be involved in membrane trafficking and/or G protein signaling opens new avenues for research.

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The nicotinic system plays an important role in ordinary cognition, particularly in attention. The main nicotinic receptor in the human brain is the heteromeric α4β2 neuronal nicotinic acetylcholine receptor (nAChR), which is distributed throughout the brain, with an especially high density in the thalamus and brainstem. Despite the important role of α4β2 nAChRs in various physiological functions and pathological conditions, their distribution in the human cortex remains poorly characterized. We assessed the in vivo distribution of α4β2 nAChRs in the human cortex in a group of seven non-smoking healthy subjects, using 2-[(18)F]F-A-85380 PET and a volume-of-interest-based analysis. We showed that cortical nAChR density was highest in the insular and anterior cingulate cortices. In functional magnetic resonance imaging studies, these two cortical regions and the thalamus have been shown to be highly correlated during the resting state and various tasks. Here, we also directly assessed nAChR density in this cingulo-insular network as defined in an independent dataset using resting-state functional connectivity, and compared it to other control-related networks, to the default mode network as well as to sensory and motor networks. Receptor density was significantly higher in the cingulo-insular network. This network has been suggested to maintain a variety of foundational capacities fundamental to cognitive function. The demonstration of a high nAChR density in the insular and anterior cingulate cortices reflects a particular neurochemical organization of the cingulo-insular network, and suggests an important role of the nicotinic receptors in its functions.

No summary available.