ED Mathématiques et Informatique
Verification and synthesis of distributed systems with weak synchronisation
by Corto MASCLE (LaBRI - Laboratoire Bordelais de Recherche en Informatique)
The defense will take place at 14h00 - Amphithéâtre LaBRI, 351 cours de la Libération
in front of the jury composed of
- Anca MUSCHOLL - Professeure des universités - LaBRI, Université de Bordeaux - Directeur de these
- Rupak MAJUMDAR - Full professor - MPI-SWS Kaiserslautern - Rapporteur
- Parosh Aziz ABDULLA - Full professor - Department of Information Technology, Uppsala University - Rapporteur
- Igor WALUKIEWICZ - Directeur de recherche - LaBRI, Université de Bordeaux - CoDirecteur de these
- Nathalie BERTRAND - Directrice de recherche - INRIA/IRISA Rennes - Examinateur
- Jérôme LEROUX - Directeur de recherche - LaBRI, Université de Bordeaux - Examinateur
- Ahmed BOUAJJANI - Professeur des universités - IRIF, Uniiversité Paris Cité - Examinateur
Distributed programs are a cause of difficulty for formal methods. The interactions of multiple components lead to a combinatorial explosion, which complicates verification. In the context of controller synthesis, this is further compounded by the fact that the strategies of one component can only take into account a partial view of the system. This has led to numerous undecidability results in the field and very high complexities in decidable cases. In this thesis, we propose an approach that allows the decomposition of verification and synthesis problems into local instances for individual processes. This approach leads to decidability results, and in some cases, to algorithms with low enough complexity to consider practical applications. We show that this method applies to distributed systems with restricted communication between components: on the one hand, systems where communication is limited to the acquisition and release of locks, and on the other hand, systems where processes communicate via broadcast. Moreover, we apply this approach to models that are quite different, where the number of processes is constant, evolves dynamically, or is parameterised.
ED Sciences de la Vie et de la Santé
Anatomical and functional characterization of neuronal projections from the basolateral amygdala and auditory cortex to the tail of the striatum
by Rodrigue ORTOLÉ (Institut des Maladies Neurodégénératives)
The defense will take place at 10h00 - Auditorium du bâtiment Broca Centre Broca Nouvelle-Aquitaine – 146 rue Léo Saignat – CS 61292 33076 Bordeaux cedex
in front of the jury composed of
- Catherine LE MOINE - Directrice de recherche - Université de Bordeaux - Examinateur
- Pierre VEINANTE - Professeur - Université de Strasbourg - Rapporteur
- Pauline BELUJON - Maître de conférences - Université de Poitiers - Rapporteur
- Emmanuel VALJENT - Directeur de recherche - Université de Montpellier - Examinateur
To understand the anatomofunctional organization of the "auditory striatum," we investigated its capacity for multimodal integration. Specifically, we explored how this structure integrates inputs from the auditory cortex and the basolateral amygdala (BLA), a key limbic region crucial for encoding information relevant to fear-related behaviors and anxiety states. Given that the BLA-to-striatum (BLA-TS) pathway remains poorly characterized, our study aimed to elucidate the anatomofunctional organization of these two key pathways, with a focus on their interaction with the dopaminergic innervation of the TS. We first sought to dissect the projections from the BLA and auditory cortex (AUV) to the TS using retrograde and anterograde tracing techniques. Our findings demonstrate that the TS receives inputs from the amygdala of both hemispheres, with a predominant contribution from the ipsilateral BLA. For the AUV, the majority of TS innervation also originates from the ipsilateral side. We further mapped the projection patterns of these pathways, showing that BLA neurons primarily target the dorsal and ventrolateral regions of the TS, areas enriched in tyrosine hydroxylase (TH). In contrast, AUV neurons mainly project to the ventral TS. Additionally, we observed that the BLA-TS pathway does not innervate PV interneurons, contrary to the AUV-TS pathway. Regarding dopaminergic innervation, our results reveal multiple sources, with the majority of inputs arising from the substantia nigra pars compacta (SNc) but also from the substantia nigra pars lateralis (SNL) and ventral tegmental area (VTA) in roughly equal proportions. This finding was confirmed through selective lesioning of dopaminergic neurons. Finally, we assessed the functional connectivity of these pathways using fiber photometry and provided functional evidence of their connectivity through electrical stimulation. Robust responses in the TS were recorded following stimulation of both the BLA and AUV. Additionally, we compared the evoked responses between the ipsilateral and contralateral BLA inputs, as well as between the AUV and BLA pathways. Overall, this study offers a detailed anatomical characterization of the AUV and BLA inputs to the TS, as well as the multiple origins of dopaminergic innervation. Functionally, it also allowed for a comparison of the glutamatergic inputs to the TS and their distinct roles in modulating striatal activity.
Therapeutic effects of the Bornavirus X protein in SOD1G93A mice
by Jeflie TOURNEZY (Neurocentre Magendie)
The defense will take place at 14h00 - Salle du conseil Neurocentre Magendie 146 Rue Léo Saignat 33000 Bordeaux
in front of the jury composed of
- Stéphanie CHEVALLIER - Maîtresse de conférences - Université de Bordeaux - Directeur de these
- Cédric RAOUL - Directeur de recherche - IMN Institut des Neurosciences de Montpellier - Rapporteur
- Richard ROBITAILLE - Directeur de recherche - Université de Montréal, Département de neurosciences - Rapporteur
- Sandrine DA CRUZ - Directrice de recherche - Leuven Brain Institute, Leuven Center for Brain & Disease Research, Research Group Molecular Neurobiology - Examinateur
- Sandrine BERTRAND - Directrice de recherche - INCIA - Examinateur
- Cyril GOIZET - Professeur des universités - praticien hospitalier - CHU Pellegrin ou Incia - Examinateur
Today, Amyotrophic Lateral Sclerosis (ALS) remains an incurable disease for which therapeutic trials have been unsuccessful. It is therefore essential to propose new therapeutic approaches that would slow the progression of the disease and prolong patient survival. Among the pathophysiological characteristics described, mitochondrial dysfunctions are one of the earliest events and could be the origin of the progressive loss of motor neurons. Restoring mitochondrial functions could therefore constitute a therapeutic area of interest to develop new therapies against this disease. With this in mind, we were interested in the X protein of the Bornavirus (BDV for Borna Disease Virus). When it targets mitochondria, the X protein inhibits the apoptosis of neurons and protects them from degeneration in an animal model of Parkinson's disease (Szelechowski et al., 2014). This neuroprotective action of the X protein resides in its last 29 carboxy-terminal amino acids which constitute the PX3 peptide. In addition, a modification to increase the mitochondrial localization of the protein X (XA4 protein) has shown improved neuroprotective effects in vitro. This thesis aimed to propose a new preclinical therapeutic approach, consisting in protecting motor neurons by using the neuroprotective properties of the Bornavirus X protein. First, we tested the neuroprotective effects of the X protein and its derived peptide PX3 in a well-characterized model of ALS, the SOD1G93A mice. Administration of the PX3 intranasally and the X intramuscularly via a viral vector (CAV2-X) slowed the progression of the disease and increased the survival of lumbar motor neurons. However, this treatment did not increase the life expectancy of the mice. Then, we used adeno-associated viruses (AAV) as gene transfer tools. More specifically, we used AAV serotype 10 (AAV10) to administer the gene encoding the X protein (AAV10-X) or its modified form, the XA4 protein (AAV10-XA4) to SOD1G93A mice. We evaluated the effects of these treatments on motor performances, life span, denervation of the neuromuscular junction, and preservation of lumbar and phrenic motor neurons (motor neurons innervating the diaphragm). Our results show that the X and XA4 proteins slowed the degeneration of lumbar motor neurons. Furthermore, while the X protein delayed the onset of motor deficits, the XA4 protein extended the life expectancy of the animals. The maintenance of motor performances in mice treated with X protein was associated with better preservation of the neuromuscular junction compared to untreated SOD1G93A mice. In addition, the administration of X or XA4 proteins to SOD1G93A mice blocks the degeneration of phrenic motor neurons, allowing them to return to values similar to the wild-type group. Although further investigations are needed to better understand the mechanisms involved in the effects of these proteins, our work demonstrates their certain therapeutic effects, on the extension of the life span, on the preservation of the neuromuscular junction, and the limitation of the degeneration of the spinal motor neurons. These studies open a new therapeutic avenue against ALS.
ED Sciences Physiques et de l'Ingénieur
Architectural design space exploration using high-level synthesis: applicability to radar processing systems
by Hugues ALMORIN (Laboratoire de l'Intégration du Matériau au Système)
The defense will take place at 10h15 - Amphi J-P. Dom IMS Bordeaux, Bâtiment A31 351 Cours de la libération 33405 Talence Cedex, France
in front of the jury composed of
- Christophe JEGO - Professeur des universités - ENSEIRB-MATMECA - Bordeaux INP, IMS UMR 5218 - Directeur de these
- Amor NAFKHA - Maître de conférences - Centrale Supelec, IETR UMR 6164 - Rapporteur
- Loïc LAGADEC - Professeur des universités - ENSTA Bretagne, Lab-STICC UMR 6285 - Rapporteur
- Dominique DALLET - Professeur des universités - ENSEIRB-MATMECA - Bordeaux INP, IMS UMR 5218 - Examinateur
- Bertrand LE GAL - Maître de conférences - ENSSAT - Université de Rennes, IRISA UMR 6074 - CoDirecteur de these
- Vincent KISSEL - Ingénieur - ARELIS - Groupe LGM - Examinateur
Since their development at the beginning of the 20th century, radar systems have been constantly evolving. Nowadays, they occupy an important place in cutting-edge systems such as air traffic control radars (ATC) and advanced driver-assistance systems (ADAS). In fact, they have become essential in many domains such as in aeronautics, space, automotive and marine. Newer radar generations aim to improve performance, and reduce development costs and reduce time-to-market in order to offer competitive electronic systems. Originally entirely analog, these systems are now integrating more and more digital functions, particularly in terms of signal processing. The description at register transfer level (RTL) of hardware accelerators implementing the calculations required to realize these radar processing chains on FPGAs is a task that represents a large part of the development cost. This is why the work carried out as part of this thesis aims to assess the relevance of using high-level synthesis (HLS) tools in the development of radar signal processing chains. A first contribution to this thesis work is a proposal for a generic model of a Fast Fourier Transform (FFT) operation. Using an HLS tool, the model's generic parameters can be used to synthesize a large number of hardware architectures with varying degrees of parallelism, according to several proposed strategies. Performance in terms of precision can also be fine-tuned, thanks to the ability to finely tune the formats of the data vectors in the model. A second contribution concerns the development of a generic model of a complete radar signal processing chain. This model also enables the performance of the resulting architectures to be fine-tuned by applying parallelization strategies at different levels. To assess their relevance, the architectures derived from the model are compared with a chain described at RTL level used in one of ARELIS's products, as well as with other chains targeting CPUs and GPUs. The results obtained from this work demonstrate the ability of HLS tools to produce reliable hardware accelerator architectures, with performances close to those described at RTL level. High-level description methods have made it easier to explore the architectural space and validate the architectures produced at different levels.
Structuring light from optical spin-orbit interaction
by Vagharshak HAKOBYAN (Laboratoire Ondes et Matière d'Aquitaine)
The defense will take place at 14h00 - Amphi Darwin Université de Bordeaux - Campus de Talence, 351 Cours de la Libération, Bâtiment Licence A22, 33400, Talence, France
in front of the jury composed of
- Thierry GROSJEAN - Directeur de recherche - FEMTO-ST Institute - Rapporteur
- Marc GUILLON - Maître de conférences - University Paris Cité - Rapporteur
- Miguel ALONSO - Professeur - Aix Marseille Université - Examinateur
- Yann MAIRESSE - Directeur de recherche - Université de Bordeaux - Examinateur
- Etienne BRASSELET - Professeure des universités - Université de Bordeaux - Directeur de these
The spin-orbit interaction for light allows coupling between the degrees of freedom associated with the polarization state of light and those associated with space. Such coupling is particularly important in media that are both inhomogeneous and anisotropic. In this work, we exploit the shaping of artificial or natural birefringence properties of optical materials such as silica, silicon nitride, silicon, or liquid crystals to shape different properties of a light beam. In particular, we demonstrate the realization of original optical elements that allow the transformation of a Gaussian beam into a Laguerre-Gauss beam. By exploiting the superposition of such modes generated by optical spin-orbit coupling, we show that it is possible to shape skyrmion-like polarization textures. Finally, by exploiting the wavelength dependence of the level of spin-orbit interaction, liquid crystal-based electro-optical devices are proposed to spectrally modulate the topology of the spatial phase distribution of the light field, opening a field of applications in the shaping of ultrashort optical pulses.
DECIPHERING THE MECHANO-PROPERTIES OF THE MEMBRANE PERIODIC SKELETON IN NEURONS USING SUPER-RESOLUTION MICROSCOPY
by Xuesi ZHOU (Laboratoire Photonique, Numérique & Nanosciences)
The defense will take place at 14h00 - L'auditorium du centre Broca Interdisciplinary Institute for Neuroscience CNRS UMR5297, 146 rue Leo Saignat 33077 Bordeaux France
in front of the jury composed of
- Brahim LOUNIS - Professeur - Université de Bordeaux - Directeur de these
- Christophe LETERRIER - Directeur de recherche - INP, UMR 7051 - Rapporteur
- Nils GAUTHIER - Docteur - IFOM - Examinateur
- Marina MIKHAYLOVA - Professor - Humboldt Universität zu Berlin - Rapporteur
- Francesca PENNACCHIETTI - Docteure - KTH Royal Institute of Technology - Examinateur
- Grégory GIANNONE - Directeur de recherche - IINS - CoDirecteur de these
- Pierre NASSOY - Directeur de recherche - LP2N - Examinateur
Mechanotransduction is the detection of mechanical forces by cells and their conversion into biochemical signals. Mechanotransduction events are key for regulating neuronal functions during physiological processes, such as development and synaptic transmission, and pathophysiological events, including traumatic brain injury and neurodegeneration, or during aging. Axons experience forces during limb flexion, but also during interactions with post-synapses and neuroglia in the brain. The membrane periodic actin-spectrin skeleton (MPS) of axons, revealed by super-resolution with a period of approximately 190 nm, could play a crucial role in neuron mechanosensing. αβ-spectrin tetramers within MPS can theoretically extend under force. The MPS is also composed of adhesion, actin-binding and signaling proteins (such as Src, CB1), some identified as mechanosensors of non-neuronal cells. My PhD aims to uncover whether the MPS in axons is a mechano-sensitive structure by studying the mechanical response and reorganizations of its components at molecular level. We recently developed the only cell stretching device compatible with super-resolution microscopy, allowing to capture the acute mechanical response of individual proteins inside mechanosensitive structures. We first adapted the stretching device to neurons to image the MPS by super-resolution and quantified its molecular deformations and reorganizations after stretch. We then applied a 30% stretch to axons at different rates (0.1s, 1s, 100s). Fast stretch (0.1s, 1s) induced an increased period of spectrin and MPS irreversible plastic deformation (0.1s) or MPS reversible elastic deformation (1s), while slow stretch (100s) did not alter the spectrin period. Thus, the MPS is a resilient mechanosensitive structure, but extremely fast deformations disrupt its molecular organization. We also revealed the mechano-dependent dissociation of adducin (actin capping protein), demonstrating an active molecular reorganization of the MPS. We are confident that, we will be able to obtain all the results to demonstrate for the first time that the MPS is a mechanosensitive structure responding to force through the reorganization of spectrin and actin-binding proteins. In collaboration with the group of Christophe Lamaze at Institut Curie (Paris, France), we adapted our strategy to assess the impact of mechanical stretching in caveolin nanoscale reorganization in endothelial cells, using super-resolution.
ED Sociétés, Politique, Santé Publique
Exposure to lipopolysaccharide-type endotoxins and the aging retina
by Petra FANG (Bordeaux Population Health Research Center)
The defense will take place at 15h00 - Amphithéâtre Louis Université de Bordeaux ISPED Campus Carreire 146 rue Léo Saignat 33076 Bordeaux cedex
in front of the jury composed of
- Cécile DELCOURT - Directrice de recherche - Université de Bordeaux - Directeur de these
- Catherine CREUZOT-GARCHER - Professeure des universités - praticienne hospitalière - CHU Dijon - Rapporteur
- Jean-François KOROBELNIK - Professeur des universités - praticien hospitalier - CHU de Bordeaux - Examinateur
- Alexander SCHUSTER - Professeur des universités - praticien hospitalier - University Medical Center Mainz - Rapporteur
Age-related eye diseases, in particular age-related macular degeneration (AMD) and glaucoma, are the leading causes of blindness in the elderly in the developed world. However, the underlying pathological mechanisms of these multifactorial diseases are not yet fully understood. The recent progress in retinal imaging, including automated segmentation of optical coherence tomography (OCT) examinations, have allowed to precisely monitor changes of the laminar structure of the retina and the optic nerve with an axial resolution of 5 µm in vivo. Recently, a potential role of altered gut microbiota in age-related eye diseases has been suggested. Such alterations of the gut microbiota may result in elevated blood concentrations of pathogens, antigens and pro-inflammatory molecules including lipopolysaccharide (LPS)-type endotoxins. The aim of this thesis was to investigate the potential associations of exposure to LPS-type endotoxins with age-related retinal diseases and morphologic changes in the Alienor cohort, a cohort of elderly French community-dwelling people, deeply phenotyped ophthalmologically. In the frame of this thesis, we reported a significant association between plasma esterified 3-hydroxy (OH)-fatty acids (FAs), a proxy of LPS-type endotoxin exposure, and incident early AMD in the Alienor cohort, suggesting that long term pro-inflammatory exposure to LPS is involved in the early pathophysiological processes of AMD. Further, we also observed a significant association between plasma 3-OH FAs and thinner peripapillary retinal nerve fiber layer, indicating an involvement of LPS in optic nerve neurodegeneration. Lastly, using longitudinal macular layer thickness data, we could also show that plasma 3-OH FAs were linked with thinner baseline inner and total macular layers over a 12-year-follow-up in the Alienor study. An additional in-depth analysis of this longitudinal morphologic data revealed that the retinal pigment epithelium – Bruch's Membrane complex was associated with incident AMD and with genetic susceptibility to AMD. Taken together, these observations highlight the potential impact of LPS and more general of human microbiota in retinal health.