ED Mathématiques et Informatique
Development of a hybrid ensemble feature selection approach to build an atlas of cancer biomarkers
by Elsa CLAUDE (LaBRI - Laboratoire Bordelais de Recherche en Informatique)
The defense will take place at 15h00 - Amphithéâtre E Université de Bordeaux, Bâtiment A29, cours de la Libération, 33405 Talence Cedex
in front of the jury composed of
- Patricia THEBAULT - Professeure - Université de Bordeaux - Directeur de these
- Emmanuelle BECKER - Professeure - Université de Rennes - Rapporteur
- Arnaud DROIT - Professeur - Centre de Recherche du CHU de Québec - Université Laval - Directeur de these
- Farida ZEHRAOUI - Maîtresse de conférences - Université d'Evry, Paris-Saclay - Rapporteur
- François COSTE - Chargé de recherche - Université de Rennes - Examinateur
- Raoul SANTIAGO - Professeur adjoint - Centre de Recherche du CHU de Québec - Université Laval - Examinateur
Biomedical research relies on omics data, such as transcriptomics, to decipher the complexity of diseases such as cancer. Traditional methods for identifying transcriptomic biomarkers associated with a phenotype make use of feature selection approaches. Hybrid Ensemble Feature Selection (HEFS) methods have become increasingly popular in the last decade for their ability to guarantee the robustness of selected variables across functional and data perturbations. However, their design remains a challenge. Our first contribution aims to evaluate the HEFS strategy by analyzing in detail 4 scenarios applied to the identification of biomarkers in various cancers from RNA-Seq transcriptomics data. These scenarios explore combinations of two variable reduction methods (differentially expressed genes and variance) with two resampling strategies (repeated holdout by stratified distribution-balanced and random stratified) for variable selection downstream of the aggregation of thousands of wrapped machine learning models signatures. Our results highlight the advantages of using HEFS approaches to identify biomarkers of complex diseases, given their ability to produce generalizable and stable results. In addition, we highlight critical considerations essential for the design of such strategies. Our second contribution is the development of an atlas of transcriptomic biomarker signatures from multiple cancers at various stages of progression. The integrated study of this atlas with proven biological annotation data (e.g. REACTOME) should enable the identification of genes of interest for various oncological phenotypes.
Efficient spectral modeling and rendering of Iridescent materials: from photonics to computer graphics
by Gary FOURNEAU (LaBRI - Laboratoire Bordelais de Recherche en Informatique)
The defense will take place at 14h00 - Ada Lovelace Inria Bordeaux Sud-Ouest, 200 Avenue de la Vieille Tour, 33400 Talence
in front of the jury composed of
- Xavier GRANIER - Professeur - Institut d'Optique Graduate School - Examinateur
- Mathieu HéBERT - Professeur des universités - Hubert Curien laboratory (UJM, CNRS, IOGS) - Rapporteur
- Adolpho MUñOZ - Associate Professor - Universidad de Zaragoza - Rapporteur
- Doris GOMEZ - Chargée de recherche - CNRS - Examinateur
This thesis focuses on the efficient spectral modeling and rendering of iridescent materials, such as Bragg mirrors and Cholesteric Liquid Crystals, for computer graphics applications. These materials exhibit vivid structural coloration due to their nanostructured periodicity, which causes complex interactions between light and the material surface. Accurately modeling these interactions is crucial for achieving realistic renderings in visual simulations. yet it is computationally challenging due to the fine spectral details involved. For Bragg mirrors, which consist of alternating dielectric layers, we introduce a model based on Pochi Yeh's analytical solution for calculating spectral reflectance. This model accurately captures the iridescent effects of Bragg mirrors by focusing on the photonic band gaps that define their high reflectivity regions. To bridge the gap between physical accuracy and real-time rendering, we developed a simplified approximation that enables efficient integration into RGB-based rendering pipelines. Additionally, we incorporated a BRDF model that accounts for surface roughness and microfacet scattering, ensuring that the appearance of Bragg mirrors reflects real-world imperfections, such as rough layered interfaces. Cholesteric Liquid Crystals (CLCs), which naturally exhibit selective reflection of circularly polarized light, present additional complexity due to their helical molecular structure. We employed the Two-Wave Approximation (TWA) to model the spectral reflectance of CLCs, providing a computationally efficient means to simulate their optical properties. This approach simplifies the representation of light interaction within the helical structure, capturing the eflectance features responsible for their unique visual effects. To complement this, we developed a BRDF model for CLCs, which simulates domain-level imperfections and variations in optical axis orientation, making the rendering of these materials both accurate and feasible in real-time applications. In conclusion, this thesis introduces novel spectral models for Bragg mirrors and CLCs, which are both physically accurate and computationally efficient. These models facilitate the rendering of complex iridescent effects within standard rendering engines, enabling real-time interaction and visual exploration of these materials. Our contributions provide a foundation for future advancements in the realistic simulation of iridescent materials in computer graphics.
Deep learning for MR to CT translation in thoracic imaging
by Arthur LONGUEFOSSE (LaBRI - Laboratoire Bordelais de Recherche en Informatique)
The defense will take place at 14h00 - Amphi du LaBRI LaBRI, Domaine universitaire, 351, cours de la Libération, 33405 Talence
in front of the jury composed of
- Pascal DESBARATS - Professeur des universités - LaBRI, Université de Bordeaux - Directeur de these
- Fabien BALDACCI - Maître de conférences - LaBRI, Université de Bordeaux - CoDirecteur de these
- Jenny BENOIS-PINEAU - Professeure des universités - LaBRI, Université de Bordeaux - Examinateur
- Nicolas NORMAND - Professeur des universités - LS2N, Université de Nantes - Examinateur
- Serge MIGUET - Professeur des universités - LIRIS, Unviersité Lumière Lyon 2 - Rapporteur
- José María MARTINEZ SANCHEZ - Professeur - Université autonome de Madrid - Rapporteur
Thoracic imaging faces significant challenges, with each imaging modality presenting its own limitations. CT, the gold standard for lung imaging, delivers high spatial resolution but relies on ionizing radiation, posing risks for patients requiring frequent scans. Conversely, lung MRI, offers a radiation-free alternative but is hindered by technical issues such as low contrast and artifacts, limiting its broader clinical use. Recently, UTE-MRI shows promise in addressing some of these limitations, but still lacks the high resolution and image quality of CT, particularly for detailed structural assessment. The primary objective of this thesis is to develop and validate deep learning-based models for synthesizing CT-like images from UTE-MRI. Specifically, we aim to assess the image quality, anatomical accuracy, and clinical applicability of these synthetic CT images in comparison to the original UTE-MRI and real CT scans in thoracic imaging. Initially, we explored the fundamentals of medical image synthesis, establishing the groundwork for MR to CT translation. We implemented a 2D GAN model based on the pix2pixHD framework, optimizing it using SPADE normalization and refining preprocessing techniques such as resampling and registration. Clinical evaluation with expert radiologists showed promising results in comparing synthetic images to real CT scans. Synthesis was further enhanced by introducing perceptual loss, which improved structural details and visual quality, and incorporated 2.5D strategies to balance between 2D and 3D synthesis. Additionally, we emphasized a rigorous validation process using task-specific metrics, challenging traditional intensity-based and global metrics by focusing on the accurate reconstruction of anatomical structures. In the final stage, we developed a robust and scalable 3D synthesis framework by adapting nnU-Net for CT generation, along with an anatomical feature-prioritized loss function, enabling superior reconstruction of critical structures such as airways and vessels. Our work highlights the potential of deep learning-based models for generating high-quality synthetic CT images from UTE-MRI, offering a significant improvement in non-invasive lung imaging. These advances could greatly enhance the clinical applicability of UTE-MRI, providing a safer alternative to CT for the follow-up of chronic lung diseases. Furthermore, a patent is currently in preparation for the adoption of our method, paving the way for potential clinical use.
Global L^p Carleman estimates
by Lotfi THABOUTI (IMB - Institut de Mathématiques de Bordeaux)
The defense will take place at 10h00 - Chaire UNESCO Lamsin Ecole Nationale d'Ingénieurs de Tunis, Rue Béchir Salem Belkhiria Campus universitaire, BP 37, 1002, Le Bélvédère, 1002, Tunis (Tunisie)
in front of the jury composed of
- Sylvain ERVEDOZA - Directeur de recherche - Université de Bordeaux - Directeur de these
- David DOS SANTOS FERREIRA - Professeur des universités - Institut Élie Cartan · Université de Lorraine - Rapporteur
- Belhassen DEHMAN - Professeur des universités - Faculté des Sciences de Tunis - Directeur de these
- Camille LAURENT - Directeur de recherche - Université de Reims Champagne Ardenne & CNRS - Rapporteur
- Nabil GMATI - Professeur des universités - ENIT Tunis - Examinateur
- Imen BHOURI - Professeure des universités - Faculté des Sciences de Monastir, Université de Monastir - Examinateur
In this thesis, we study $L^p$ Carleman inequalities for elliptic problems and their applications to the quantification of unique continuation with respect to perturbations of the Laplacian. We first focus on $L^p$ Carleman inequalities on a strip of $R^d$ $(dgeq 3)$, denoted $mathcal{S}:= (0,1) imes R^{d-1}$, for the Laplacian. Using the Fourier transform and a factorisation of the conjugate operator, we reduce the proof of these inequalities to the construction of a parametrix for the Laplacian problem with boundary conditions. Utilising this parametrix, we first reprove classical $L^2$ Carleman inequalities for the Laplacian. Then, applying harmonic analysis techniques, particularly the Fourier restriction theorem to establish $L^p-L^q$ type continuity results, we obtain $L^p - L^q$ estimates for this parametrix. We then apply these methods to the case of interest, namely $L^p$ Carleman inequalities for the Laplacian defined on $Omega$, a bounded and regular open subset of $R^d$ $(d geq 3)$, with a right-hand side $f_2 + f_{2 *'} + div F$, $f_2 in L^2(Omega), , f_{2 *'} in L^{ frac{2d}{d+2}}(Omega), , F in L^2(Omega; C^{d})$, and a Dirichlet condition $g in H^{frac{1}{2}}(partial Omega)$. We establish two global Carleman estimates: one on the $H^1$ norm of the solution and another on its $L^{frac{2d}{d-2}}$ norm, in terms of weighted $L^2$ norms of $f_2$ and $F$, the $L^{frac{2d}{d+2}}$ norm of $f_{2 *'}$, and the $H^{frac{1}{2}}$ norm of $g$. This allows us, for example, to obtain a quantification of unique continuation for solutions of $Delta u = V u + W_1 cdot abla u + div(W_2 u)$ in terms of the norms of $V$ in $L^{q_0}(Omega)$, $W_1$ in $L^{q_1}(Omega)$, and $W_2$ in $L^{q_2}(Omega)$ for $q_0 in (d/2, infty]$ and $q_1$ and $q_2$ satisfying either $q_1, , q_2 > (3d-2)/2$ and $frac{1}{q_1} + frac{1}{q_2}< 4(1-frac{1}{d})/(3d-2)$, or $q_1, , q_2 > 3d/2$. In the third part, we study a quantification of unique continuation for solutions of the equation $Delta u = V u + W_1 cdot abla u + div(W_2 u)$ but with first-order potentials that are more singular in the limit integrability class. In particular, we consider the case where $W_1 in L^{q_1}$ and $W_2 in L^{q_2}$, with $q_1 > d$ and $q_2 > d$. Using T. Wolff's lemma on Euclidean measures and a refined version of Carleman estimates, we obtain unique continuation quantification results for solutions $u$ of $Delta u = V u + W_1 cdot abla u + div(W_2 u)$ in terms of the norms of the potentials.
ED Sciences Chimiques
In vitro aggregation of the amyloid protein Tau and study of its impact on membrane models using various biophysical methods
by Vicky URY (Institut de Chimie & de Biologie des Membranes & des Nano-objets)
The defense will take place at 13h00 - amphithéâtre IECB IECB, 2 rue Robert Escarpit, 33600 Pessac
in front of the jury composed of
- Sophie LECOMTE - Directrice de recherche - Université de Bordeaux - Directeur de these
- Sylvie NOINVILLE - Chargée de recherche - CNRS Paris - Rapporteur
- Lorena REDONDO-MORATA - Chargée de recherche - INSERM Marseille - Rapporteur
- Christine GRAUBY-HEYWANG - Professeure des universités - Université de Bordeaux - Examinateur
- Jehan WAEYTENS - Assistant professor - Université Libre de Bruxelles - Examinateur
- Michael MOLINARI - Professeur des universités - Université de Bordeaux - CoDirecteur de these
Neurodegenerative diseases, such as Alzheimer's and Parkinson's, affect cognitive and motor functions. They are characterized by a progressive loss of neurons, with no possibility of regeneration. With an aging population, these predominantly age-related diseases represent a major societal challenge. The lack of early diagnosis, effective treatments, and understanding of the underlying mechanisms highlights the need for further investigation. Patients suffering from these diseases exhibit abnormal protein accumulations in the form of insoluble aggregates, within or near brain cells. Although each proteinopathy presents specific aggregates, they share common features, notably their amyloid structure. These amyloids, formed by the misfolded protein monomers' self-assembly through stacking, adopt a characteristic cross-β structure. Several pathogenic amyloid proteins have been identified and are associated with various neurodegenerative diseases. The Tau protein, implicated in Alzheimer's disease and more broadly in a group of dementias known as tauopathies, is primarily located in neurons, where it stabilizes microtubules, structural elements of the cellular cytoskeleton. However, under pathological conditions, Tau dissociates from the microtubules, becomes hyperphosphorylated, and forms fibrillar amyloid aggregates. The exact mechanisms of this aggregation remain poorly understood. The study of Tau aggregation relies on the in vitro production of amyloid fibers. Due to its high solubility associated with its positive charge, fiber formation requires the addition of polyanionic molecules, called cofactors, such as heparin (a polysaccharide), RNA, or lipids. However, uncertainties remain regarding the exact role of these cofactors: do they simply catalyze aggregation, or are they integrated into the fiber structure? If so, what impact does this have on the morphology of the aggregates? Tau's ability to aggregate in the presence of lipids raises questions about its behavior in relation to the different membranes of neurons. Tau's interaction with plasma membranes has been demonstrated and may play a role in both physiological and pathological processes. Does Tau, in the presence of anionic lipids, compromise membrane integrity? What about non-anionic lipids? To address these questions, this thesis project combines several biophysical approaches: attenuated total reflection Fourier-transform infrared spectroscopy (ATR-FTIR), atomic force microscopy (AFM), transmission electron microscopy (TEM), and plasmon waveguide resonance (PWR). The study is structured around two main axes: (i) characterizing Tau aggregation in the presence of different anionic cofactors (heparin, RNA, phospholipids) and studying their impact on fiber morphology; (ii) assessing the effect of Tau's interaction with lipid membranes of varying compositions on membrane integrity. The results of this thesis provide new insights into the pathogenic mechanisms of Tau and may contribute to a better understanding of tauopathies as well as the development of therapeutic strategies.
Development of a high throughput experimentation approach for solid-state lithium ionic conductors
by William BERTHOU (ICMCB - Institut de Chimie de la Matière Condensée de Bordeaux)
The defense will take place at 14h00 - Amphithéâtre de l'ICMCB 87 Avenue du Dr Albert Schweitzer, 33600 Pessac
in front of the jury composed of
- Frédéric LE CRAS - Cadre scientifique des EPIC - Université Grenoble Alpes - Directeur de these
- Vincent MOTTO-ROS - Professeur associé - Université Claude Bernard Lyon 1 - Examinateur
- Christian JORDY - Cadre scientifique - SAFT, TOTAL Group - Examinateur
- Dany CARLIER-LARREGARAY - Professeure - Institut de Chimie de la Matière Condensée de Bordeaux, CNRS, Université de Bordeaux, Bordeaux INP - CoDirecteur de these
- Thierry BROUSSE - Professeur - Institut des Matériaux Jean Rouxel de Nantes - Rapporteur
- Mickael DOLLE - Professeur - Université de Montréal - Rapporteur
- Cyril AYMONIER - Directeur de recherche - Institut de Chimie de la Matière Condensée - Examinateur
The development of new materials for electrochemical storage and the improvement of their properties is driven by a relentless quest to make batteries safer, more compact, more environmentally friendly and, if possible, less expensive. Most research in this field is based on an iterative trial-and-error approach, which is slow and limited when it comes to exploring increasingly complex multi-element systems. An alternative approach, called 'high-throughput screening', speeds up the identification of new compounds. It is based on the rapid preparation of large quantities of samples using combinatorial chemistry and their physicochemical and functional characterization using rapid, automated protocols. The aim of this work was to develop such an approach for the study of lithium-ion conducting materials. Magnetron co-sputtering was chosen to carry out the combinatorial synthesis of libraries of these materials in thin films on wafer. Various techniques have been developed to characterize these sets of materials in terms of dimensional, chemical, structural and ion transport properties. In particular, an innovative chemical analysis technique for thin films has been developed: laser induced plasma spectroscopy (LIBS). The approach was developed using amorphous LixPOyNz compounds, conventionally synthesized by cathode sputtering, as a first case study. Once established, this approach allowed the study of LiPO(N) and then LiSiPO(N) systems over extended compositional ranges. This work made it possible to establish correlations between composition - structure - electrical or mechanical properties on systems that had previously been studied in a fragmentary fashion. Finally, a brief study of the Li-Al-Ti-Si-P-O system allowed us to make our first incursion into the field of crystalline and glass-ceramic materials and to use X-ray diffraction as a high-throughput structural characterization method on these libraries of thin film materials.
Structuring the electrical properties of a glassy surface applied to the control of the orientation of a nematic mesophase
by Alexis MAILLARD (Institut des Sciences Moléculaires)
The defense will take place at 15h00 - Salle de réunion 3ème EST Institut des Sciences Moléculaires Bâtiment A12, 351 Cours de la Libération 33405 Talence Cedex
in front of the jury composed of
- Marc DUSSAUZE - Directeur de recherche - Université de Bordeaux - Directeur de these
- Andréa PIARRISTEGUY - Professeure des universités - Université de Montpellier - Rapporteur
- Jean-René DUCLERE - Professeur des universités - Université de Limoges - Rapporteur
- Alice BERTHELOT - Maîtresse de conférences - Université Claude Bernard Lyon 1 - Examinateur
- Younès MESSADEQ - Professeur des universités - Université Laval - Examinateur
- Tigran GALSTIAN - Professeur des universités - Université Laval - Directeur de these
The work performed in this thesis focused on the development of a hybrid photonic system combining a novel functionalized vitreous material and a nematic mesophase of liquid crystals. The main component of the hybrid system is a commercial soda-lime glass, whose surface potential is structured via a plasma-assisted thermoelectric poling treatment. This is made possible through the use of a microstructured electrode. In a second phase, the electrically structured vitreous substrate is used to produce a simple photonic system that is a liquid crystal cell. These cells are designed to observe the alignment induced by the poled glass on the molecules. At this stage, the goal is to better understand the origin of the liquid crystal alignment on poled glass, which involves a multimodal characterization of the hybrid system, broken down into two main axis: • A structural study of the functionalized glass • A study of the molecular organization in contact with the poled substrate The first axis is achieved through a thorough spectroscopic analysis of the poled substrate. Techniques such as polarized second harmonic generation microscopy, polarized Raman microscopy, and composition analysis by electron microprobe establish a clear link between the electrical function of the material and its atomic structure. The second axis, concerning molecular organization, is conducted using polarized light microscopy and polarized Raman spectroscopy techniques to measure molecular orientation. Furthermore, the application of an orientation distribution model allows for a comparison of molecular alignment between samples and with a reference planar alignment cell. The initial work of the thesis aimed to reproduce results previously obtained on similar systems, then to increase the size of the structures formed when liquid crystals come into contact with the substrate. In this context, the glass was poled using an electrode in the form of a microstructured grid. The results show that the obtained electrical function is highly oriented on the glass and that the liquid crystals follow this alignment by forming triangular patterns, with similar molecular flatness relative to the substrates for two poling grid sizes. These preliminary studies led to the use of a new wire-shaped electrode. The study of the poled glass structure shows a strong link between the appearance of a planar space charge and plasma production during the treatment. The origin of the space charge is further discussed based on Raman measurements. Subsequently, when poled glasses with wire anodes are brought into contact with liquid crystals, homogeneous alignment domains in the form of bands are produced. A strong correlation between domain size and poling voltage was observed, while the molecular alignment remained the same for all treatments. Finally, the design of dynamic In-plane Switching (IPS) cells with poled substrates allows for the comparison of the anchoring of molecules on the surface with a reference cell designed with commercially available substrates.
Behavior and modeling of CMC/EBC system under thermochemical and mechanical loadings in aircraft engines
by Lallie QUEMERAS (Laboratoire des Composites ThermoStructuraux)
The defense will take place at 14h00 - Amphithéâtre LCTS – 3, Allée La Boétie – Domaine Universitaire – 33600 PESSAC – France
in front of the jury composed of
- Francis REBILLAT - Professeur des universités - Université de Bordeaux - Directeur de these
- Vincent MAUREL - Directeur de recherche - Centre des matériaux - Rapporteur
- Guillaume COUéGNAT - Ingénieur de recherche - LCTS - CoDirecteur de these
- Thomas VANDELLOS - Docteur - Safran Ceramics - CoDirecteur de these
- Benoit PANICAUD - Professeur des universités - Université de Technologie de Troyes - Rapporteur
- Clara DESGRANGES - Ingénieure de recherche - CEA Paris Saclay - Examinateur
- Daniel MONCEAU - Directeur de recherche - CIRIMAT - Examinateur
The aerospace industry is currently facing environmental and social issues. In order to address these issues, and in particular to reduce the production of greenhouse gases, new materials are being considered to replace the metallic superalloys currently used in engines. To this end, Ceramic Matrix Composites (CMC) have demonstrated their potential as a replacement for these alloys: their high temperature mechanical properties enable the increasement of the temperature reached in engines, thereby reducing fuel consumption. However, at high temperatures, these composite parts undergo significant surface recession through reaction with the water vapor present in the engine environment. This recession reduces their service lifetime. To protect them, an environmental barrier (EBC) is deposited on their surface. During engine thermal cycles, various physicochemical and thermomechanical mechanisms can damage the coating. This thesis focuses on two main types of damage: oxidation/corrosion damage to the bonding undercoat and thermomechanical stresses across this multilayer system: bondcoat/TGO/EBC. The system studied is a SiCf/SiCm CMC successively coated with a silicon bondcoat and an yttrium disilicate coating. At high temperatures and in an oxidizing atmosphere, the silicon oxidizes, forming a silica layer under the EBC. Oxidation/corrosion tests (under humid air) were carried out at different environmental conditions on polished and coated silicon samples to characterize the effect of interface roughness and coating efficiency on oxidation kinetics and system damage. Morphological observations and diffusion data are then used in finite element (FE) modeling to predict the behavior of the CMC/EBC system as a function of time, temperature and corrosive conditions. This modeling relies on a phase field to describe the physicochemical evolution of the system with the advancement of the Si/TGO interface over time as a function of environmental conditions.
Understanding polymer blends for use as mixed ion-electron conductors
by Yasmina AL YAMAN (Laboratoire de Chimie des Polymères Organiques)
The defense will take place at 13h30 - Amphi. B5 B5, All. Geiffroy Saint-Hilaire, 33600 Pessac
in front of the jury composed of
- Cyril BROCHON - Professeur - Université de Bordeaux - Directeur de these
- David MECERREYES - Professeur - University of the Basque Country - Rapporteur
- Natalie STINGELIN - Professeure - Georgia Institute of Technology - CoDirecteur de these
- Laure BINIEK - Chargée de recherche - Université de Strasbourg - Rapporteur
- Laurence VIGNAU - Professeur - Bordeaux INP - Examinateur
- Laurent RUBATAT - Maître de conférences - Université de Pau et des Pays de l'Adour - Examinateur
The integration of biology and electronics for applications like implantable medical devices and wearable electronics relies on OECTs. However, OECT performance is often limited by inefficient ion transport. This study aimed to enhance OECT performance by increasing hydrophilicity through polymer blending. Initial challenges with newly synthesized hydrophilic polymers, such as solubility issues and poor doping behavior, led to exploring blends of the hydrophobic polymer poly(3-hexylthiophene) (P3HT) with hydrophilic components like P3HT-b-PEO and polyethylene oxide (PEO). While P3HT alone showed limited performance, blending with either P3HT-b-PEO or PEO enabled clear transistor behavior. Notably, P3HT in the block copolymer acts as a compatibilizer, enhancing blend stability and device performance compared to PEO alone. Higher molecular weight P3HT blends exhibited better stability and faster response, likely due to increased polymer entanglement. When applying this approach to the rigid polymer PDPP2T-TT-OD, both blends (with P3HT-b-PEO or PEO) demonstrated similar stability results. This suggests that the rigid backbone of PDPP2T-TT-OD limits compatibility and affects the stability of both types of blends. Overall, this research highlights the effectiveness of polymer blending in optimizing OECT performance, providing a viable pathway for developing advanced bio-interfacing electronic devices.
Janus polymersomes: rational design, preparation and asymmetric functionalization towards self-propelled drug delivery systems
by Eloïse EQUY (Laboratoire de Chimie des Polymères Organiques)
The defense will take place at 13h30 - Amphi 1 Ecole Nationale Supérieure de Matériaux, d'Agroalimentaire et de Chimie, ENSMAC (ex ENSCBP) 16 Avenue Pey-Berland 33607 Pessac Cedex France
in front of the jury composed of
- Sébastien LECOMMANDOUX - Professeur des universités - LCPO, Université de Bordeaux - Directeur de these
- Min-Hui LI - Directeur de recherche - Institut de Recherche de Chimie Paris (IRCP) - Rapporteur
- Christophe TRIBET - Directeur de recherche - ENS – Département de chimie - Rapporteur
- Katharina LANDFESTER - Professeur des universités - Max Planck Institute for Polymer Research - Examinateur
- Chrystel FAURE - Professeur des universités - CBMN, Université de Bordeaux - Examinateur
Mimicking the properties of living cells in artificial protocells has attracted significant interest, particularly for replicating motility and directional swimming for applications in smart therapeutics. Due to their vesicular and stable morphology, polymersomes hold great promise for drug delivery, and the introduction of asymmetry is crucial to enable self-propulsion. While several approaches, such as phase separation within the membrane, have been used to create asymmetric polymersomes, the selection of appropriate polymers remains a challenge. This PhD thesis aims at designing asymmetric, Janus-like polymersomes capable of self-propulsion, and powered by enzymatic glucose decomposition. We describe the development of Janus Giant Unilamellar Vesicles (JGUVs) through phase separation within the membrane of two distinct block copolymers comprising chemically incompatible hydrophobic blocks. We demonstrate, using the Flory-Huggins theory, that copolymers can be rationally selected and designed to self-assemble into asymmetric polymersomes, with tunable phase separation driven by parameters such as composition, molecular weight, and temperature. Our predictive method proves to be effective for both solvent-free and solvent-switch self-assembly processes, enabling the elaboration of generic phase diagrams correlating mixing free energy with polymersome morphology, providing valuable insights for JGUVs design. We also evidence that the presence of solvent during the vesicle formation broadens the range of incompatible polymers that can be used. Additionally, we successfully control, thanks to extrusion, the vesicle size while preserving their Janus morphology and evidence that the resulting JGUVs could be stable for several months. Furthermore, we asymmetrically functionalized JGUVs with glucose oxidase enzymes via click-chemistry, and a preliminary study on their dynamic behavior in the presence of glucose is presented, looking forward to their potential use as micromotors.
ED Droit
The mutations of filiation
by Marion DAMY (CENTRE EUROPÉEN DE RECHERCHES EN DROIT DES FAMILLES, DES ASSURANCES, DES PERSONNES ET DE LA SANTÉ)
The defense will take place at 14h30 - des thèses Bâtiment C, 16 avenue Léon Duguit, CS 50057, 33608 Pessac cedex
in front of the jury composed of
- Adeline GOUTTENOIRE - Professeure des universités - Université de Bordeaux - Directeur de these
- Pascale DEUMIER - Professeure des universités - Université Jean Moulin Lyon III - Rapporteur
- Jérémy HOUSSIER - Professeur des universités - Université de Reims Champagne-Ardenne - Rapporteur
- Hugues FULCHIRON - Professeur des universités - Université Jean Moulin Lyon III - Examinateur
- Marie LAMARCHE - Professeure des universités - Université de Bordeaux - Examinateur
Even before the 2009 ratification law, which reformed the 2005 filiation ordinance, the subject was already facing new challenges. Developments in technical and scientific progress, as well as the expansion of fundamental rights, indeed, are disrupting the balance between collective and individual issues inherent to the legal framework of family relationships. These combined influences, which are more focused on the individual, are intensifying the subjectivisation described by dean Carbonnier. Given that this phenomenon has reached a new stage since the liberalization of marriage in 2013, the aim of this study is to examine the resulting mutations in the filiation laws. It emerges that the heteronormative model is gradually fading, implying with the liberalization of the subject, more subtly, to a personalization of its application. In the filiation law, the phenomenon of subjectivisation can therefore be seen both upstream and downstream of the law. At the drafting stage, the content of the law struggles to set limits, whereas at the application stage, the limit set against the individual will have to be more tangible and justified. As a result, the control of the field shifts in favor of the judge, as close as possible to individual situations.
EVIDENCE COLLECTION AND STATE INVESTIGATION IN THE ERA OF THE “POLICE, INTELLIGENCE SERVICES, PRIVATE CORPORATIONS” ECOSYSTEM. In search of the protection of fundamental human rights
by Claudiu POPA (INSTITUT DE SCIENCES CRIMINELLES ET DE LA JUSTICE)
The defense will take place at 9h00 - Salle A9-162 Faculté de droit de l'Université de Sherbrooke, bâtiment A9, 2500 Bd de l'Université, Sherbrooke, Québec, J1K 2R1, Canada.
in front of the jury composed of
- Olivier DECIMA - Professeur des universités - Université de Bordeaux - Directeur de these
- Arthur OULAÏ - Professeur des universités - Université de Sherbrooke - Directeur de these
- Charlotte CLAVERIE-ROUSSET - Professeure des universités - Université de Bordeaux - Examinateur
- Alexandre STYLIOS - Professeur des universités - Université Laval - Examinateur
- Édouard VERNY - Professeur des universités - Université Paris-Panthéon-Assas - Rapporteur
- Vincent GAUTRAIS - Professeur des universités - Université de Montréal - Rapporteur
The digital doping of police investigations in the last 20 years seems to be enhanced by the collection of evidence carried out as part of the emergence of a techno-legal symbiosis. This symbiosis is supported by civil contractual law, by laws concerning the protection of personal information which seem to offer frameworks for the communication of evidence and not its limitation, by private corporations which are increasingly participating in criminal investigations of criminal offenses carried by the State, through the use of personal data as evidence, for whose consent at the origin of their obtaining raises serious questions as to its free and informed nature, obtained by contractual means sometimes in context of constraint or necessity, as well as by the increasingly frequent participation of intelligence services in police investigations and by the use of international intelligence-sharing agreements. Faced with the increased powers of the State and its investigative tools, the fundamental rights of the individual are put to the test. It is in this context, in the digital age and omnipresent technology, that this thesis seeks correlative protection of fundamental rights for the individual.
ED Sciences de la Vie et de la Santé
Development of whole Pinot Noir berries on several Climats de Bourgogne through the prism of their metabolism.
by Antoine LAPORTE (BFP - Biologie du Fruit et Pathologie)
The defense will take place at 9h00 - Amphithéâtre Colette & Josy Bové INRAE Bordeaux-Aquitaine Campus de la Grande-Ferrade 71 Avenue Edouard Bourlaux 33140 Villenave-d'Ornon
in front of the jury composed of
- Marielle ADRIAN - Professeure - Université de Bourgogne - Rapporteur
- Charles ROMIEU - Chargé de recherche - Université de Montpellier - Rapporteur
- Anne GOELZER - Ingénieure de recherche - Université de Toulouse - Examinateur
- Éric GOMèS - Professeur - Université de Bordeaux - Examinateur
Grapes for winemaking hold significant economic importance in France and stu- dying their development is of growing interest given the increasingly severe and frequent climate changes. Bourgogne is no exception to this reality, and studying Pinot Noir, a red grape variety endemic to the region, in its environment with regard to specific regional factors—such as the Climats—has become a crucial area of study. We therefore examined the development of Pinot Noir over two consecutive years, characterized by higher-than-average seasonal temperatures and an excellent sanitary condition of the harvest in Burgundy. Samples were taken at regular intervals from five production plots, from fruit set to harvest. Various factors influencing grape develop- ment were recorded, including rootstocks, plots, weather conditions as well as sun exposure, the position of the berries on the bunch, their weight and size. We measured the main components of the biomass, which explained up to 80% of the berry's dry mass, and analyzed them through the lens of these various factors. We were able to determine the hierarchy and intensity of the impact of these factors on berry development and their com- ponents. The effect of the vintage was omnipresent throughout development and on almost all components, with a particularly strong impact on tartrate concentration, which was more than 2.5 times higher in 2022 than in 2023, reaching about 270 mg.gDM-1. We concluded that this higher accumulation was due to water stress experienced by the vine before and during the green growth phase of the berries, highlighting the importance of the pre-season on the technological characteristics of the harvest. However, the vintage effect diminishes at the end of growth when the berries are fully ripe. We also suggest that the plot plays a role, particularly in the nitrogen cycle, especially at the beginning and end of development. Lastly, rootstocks, together with the plots, play a major role in the accumulation of sugars in the berries, and it is the vigor conferred to the vine by the plant material that determines the order of ripening across the plots. For more precision regarding certain factors of interest for winemaking, we determined the concentration of 33 polyphenols. This allowed us to identify a higher quantity of acids accompa- nied by earlier anthocyanin accumulation in 2022 and a greater quantity of catechin monomers in 2023. The acquisition of transcriptomic data and its integration aligned with the previous observations. Finally, according to all the metrics used, the developmental sequence consistently explained the greatest variability, with a noticeable synchronization in the observations of the last two or three sampling stages, depending on the type of data used. Moreover, through a generalized linear model, we were able to predict plot-related factors with greater accuracy in 2022 than in 2023, indicating that water stress likely enhanced the expression of the terroir. However, de- velopmental stages were predicted with greater precision using the 2023 dataset, reflecting an almost schematic development of the berries under low to no stress conditions and a much less predictable impact of the plots or plant material in the absence of perceived stress. It would now be interesting to integrate this data into a genome-scale metabolic model reconstructed for this purpose, in order to more precisely study the variations in carbon fluxes that could explain these different observations.
Role of clonal hematopoiesis of indeterminate potential (CHIP) in the pathophysiology of cardiovascular diseases
by Mélody DUFOSSEE (Biologie des maladies cardiovasculaires)
The defense will take place at 14h00 - salle de conférence INSERM UMR1034 "Biologie des Maladies Cardiovasculaires" 1 avenue Magellan 33600 Pessac
in front of the jury composed of
- Marie-Antoinette SEVESTRE-PIETRI - Professeure des universités - praticienne hospitalière - Université de Picardie Jules Verne - Rapporteur
- Hafid AIT-OUFELLA - Professeur des universités - praticien hospitalier - Université Paris Cité - Rapporteur
- Pierre HIRSCH - Maître de conférences - praticien hospitalier - Sorbonne université - Examinateur
- Catherine SAWAI - Chargée de recherche - université de Bordeaux - Examinateur
Aging is associated with the acquisition by hematopoietic stem cells (HSCs) of somatic muta-tions and chromosomal alterations. In some cases, the acquisition of one of these abnormali-ties gives the HSC a self-renewal and proliferation advantage leading to the development of clonal hematopoiesis. The term Clonal Hematopoiesis of Indeterminate Potential (CHIP) characterizes the detection in the blood of a clone carrying a somatic mutation in one gene associated with leukemias with a variant allele frequency ≥2% but in the absence of any di-agnostic criteria for a hematological malignancy. CHIP have been associated with increased overall mortality which would be mainly related to the occurrence of cardiovascular events (CVE). CHIP would particularly participate in the pathophysiology of atherothrombosis and heart failures (HF) by exacerbating the inflammatory profile of mutated monocytes and macrophages with overexpression of interleukins 1β, 6, and 18, following hyperactivation of the NLRP3 inflammasome. More recently, the mosaic loss of Y chromosome (mLOY) in leu-kocytes has also been associated with CVE by promoting a pro-fibrotic phenotype of macro-phages. In a first line of work, we studied the association of CHIP and mLOY with the risk of myocar-dial infarction (MI+) in a cohort of 446 participants. Our study did not find a statistically sig-nificant association between CHIP nor mLOY and inflammation, atherosclerosis, or the inci-dence of atherosclerotic events, suggesting that the effect of CHIP or mLOY is less important than that of traditional cardiovascular risk factors. However, we observed that men who are carriers of CHIP might develop MI earlier if they do not carry mLOY on the other hand. In a second line of work, we investigated in mouse models the role of CHIP in the pathophys-iology of heart failure with preserved ejection fraction (HFpEF). We used an HFpEF induction protocol combining a high-fat diet and angiotensin II infusion applied to mice with or without CHIP. Our experiments did not show a significant effect of CHIP in inducing HFpEF. Finally, to investigate whether cell types other than monocytes and macrophages are in-volved in the pathophysiology of CVE associated with CHIP, we aimed to determine whether neutrophils carrying CHIP mutations could play a role in the occurrence of CVE, particularly through the release of Neutrophil Extracellular Traps (NETs). In a sample of 81 MI+ patients, the presence of CHIP was significantly associated with an increase in plasmatic markers of NETs (citrullinated histone H3 and myeloperoxidase + DNA complex). In mouse models, CHIP was associated with a non-significant increase in the percentage of NETs formed after ex vivo stimulation of neutrophils with ionomycin.
Roles of the CB1 receptor and the endocannabinoid system in the retina.
by Sandra BERIAIN VIGURIA (Neurocentre Magendie)
The defense will take place at 12h00 - Room Adela Moyua Science and Technology Faculty. Barrio sarriena s/n 48940, Leioa, Bizkaia
in front of the jury composed of
- Frank KIRCHHOFF - Full professor - Saarland University - Rapporteur
- Stefanie HAUCK - Directrice de recherche - Helmholtz Zentrum München - Rapporteur
- Nagore PUENTE BUSTINZA - Directrice de recherche - Universidad del País Vasco/Euskal Herriko Unibertsitatea - Examinateur
- Guillaume FERREIRA - Directeur de recherche - Université de Bordeaux - Examinateur
- Pedro DE LA VILLA POLO - Full professor - Universidad de Alcalá - Examinateur
The retina is a specialized tissue that functions as a sensory extension of the central nervous system. Its primary role is to convert light into electrical signals for visual processing. Composed of five types of neurons and glial cells, it includes photoreceptors (rods and cones), which capture light and send signals to other retinal cells (bipolar, horizontal, and amacrine cells) before reaching retinal ganglion cells. These ganglion cells transmit visual information to the brain via the optic nerve. Supporting cells, such as Müller glia, offer structural, metabolic, and functional aid to the retina. Retinal disorders, like glaucoma and diabetic retinopathy, are common causes of irreversible blindness due to neuronal degeneration. Recently, researchers have identified the endocannabinoid system in the retina, a neuromodulatory system involving cannabinoid receptors (CB1 and CB2), endogenous ligands, and enzymes for synthesis and degradation. This system, crucial for modulating synaptic transmission, has been well-studied in the central nervous system but is now gaining attention for its potential role in retinal function. Notably, cannabinoid receptors (CB1) have been found in all retinal neurons, though their presence in Müller glia remains controversial. The system is thought to regulate neurotransmitter release, particularly glutamate, essential for visual processing and light sensitivity. The endocannabinoid system may also have therapeutic potential in retinal diseases, as cannabinoids are believed to have neuroprotective effects, modulating inflammation and stress responses. Its presence in Müller glia suggests the system could influence synaptic modulation and communication between retinal neurons and glial cells. Research into this system's role in retinal function and pathology has used mice models for both in vitro and in vivo experiments. These studies confirmed CB1 receptor distribution across retinal cells and investigated its role in mitochondrial respiration and visually-evoked defensive behaviors. For instance, CB1 receptor activation influenced mitochondrial function in glial cells, hinting at its potential impact on retinal energy metabolism, though deletion of the receptor did not impair overall mitochondrial function. Additionally, CB1 receptors were shown to affect responses to certain visual stimuli related to defensive behaviors, such as the looming test, which mimics predator approach, while not influencing other behaviors, like spatial navigation or auditory fear responses. In the context of retinal ischemia/reperfusion injury, the deletion of CB1 receptors did not significantly affect retinal ganglion cell survival. However, sex-dependent responses to ischemic stress were observed, indicating that males and females may respond differently to such injuries. Overall, this research underscores the complex role of the endocannabinoid system in retinal health, particularly through its effects on synaptic modulation, visual processing, and response to pathological conditions. It suggests that further exploration into cannabinoid signaling could open up new avenues for treating retinal diseases.
Cortical mechanisms of comorbidity between pain sensitization and attention-deficit/hyperactivity disorder (ADHD) in a mouse model
by Sarah BOU SADER NEHME (Institut des Maladies Neurodégénératives)
The defense will take place at 14h00 - Amphitéâtre BROCA Université de Bordeaux Centre Broca Nouvelle-Aquitaine 146 rue Léo Saignat – CS 61292 33076 Bordeaux cedex
in front of the jury composed of
- Marc LANDRY - Professeur - Université de Bordeaux - Directeur de these
- Ana Maria SANCHEZ PEREZ - Professeure - Universitat Jaume I - Rapporteur
- Jeffrey GLENNON - Professor - University College Dublin - Rapporteur
- Walid HLEIHEL - Professeur - Université Saint-Esprit de Kaslik - Directeur de these
- Agnès NADJAR - Professeure - Université de Bordeaux - Examinateur
- Tania BITAR - Assistant professor - Université Saint-Esprit de Kaslik - Examinateur
- Annabelle REAUX-LE-GOAZIGO - Professeure - Institut de la Vision - Examinateur
- Laurent GALINEAU - Associate Professor - Université de Tours - Examinateur
Attention deficit/hyperactivity disorder (ADHD) and chronic pain are two complex conditions of multifactorial origins. Clinical and preclinical studies support an association between these two syndromes. However, the mechanisms underlying their comorbidity are not well understood. Previous findings from our team demonstrated a hyperactivity of the neurons of the anterior cingulate cortex (ACC) and a deregulation of the ACC-posterior insula (PI) pathway in ADHD-like conditions. Growing evidence also suggests a role for neuroinflammation in this concomitance. Our hypothesis thus suggests that neuroinflammation triggers an enhanced neuronal activity in the ACC that sensitizes pathways involved in ADHD symptoms and pain perception. Therefore, this Ph.D. work aims to elucidate the inflammatory mechanisms that may underlie ADHD and its associated pain sensitization, with an interest in the role of the purinergic P2X4 receptor. To address this question, we generated an ADHD-like mouse model through the unilateral intracerebroventricular injection of 6-hydroxydopamine (6-OHDA) at P5. Two-month-old wild-type male and female mice were sacrificed, their brains were extracted, and their ACC and PI were dissected. Fixed tissues were used to study microglial and astrocytic morphology while fresh tissues were utilized for transcriptomic, proteomic, and phosphoproteomic investigations. Moreover, mice with a total knock-out of the P2X4 receptor were tested for thermal and mechanical pain sensitization, in addition to hyperactivity. Fixed tissues of the ACC were used to study changes in microglial morphology while fresh tissues of the ACC and PI were utilized for transcriptomic analyses. Regarding the identification of inflammatory mechanisms in our ADHD-like mouse model, our results report (i) changes in microglial and astrocytic morphology, associated with cellular reactivity, in the ACC of 6-OHDA mice, (ii) the presence of a pro-inflammatory environment in the ACC and PI of 6-OHDA mice, (iii) modifications in protein expression and kinase (serine-threonine and tyrosine) activity in the ACC and PI of 6-OHDA mice, and correlated with impairments in axon guidance, apoptosis, cytoskeleton dynamics, signaling cascades, neurotrophins, and neurotransmitter systems, and (iv) alterations in protein interactions and, therefore, neuronal-astrocytic communication in the ACC of 6-OHDA mice. Finally, data integration identified four processes impaired in the ACC and PI of 6-OHDA males and females: apoptosis, axon guidance, synaptic plasticity (long-term potentiation), and growth of neuronal components. Interestingly, alterations in these processes were not only linked to ADHD and chronic pain conditions but also associated with Eph/ephrin bidirectional signaling cascades. Our findings also indicate a role for the P2X4 receptor in the worsening of ADHD hyperactivity symptom and the induction of morphological changes in microglial cells that correlate with cellular reactivity. However, it exerts a protective effect by limiting the expression of pro-inflammatory molecules, possibly from non-microglial cells. In conclusion, our work provides interesting insights into the inflammatory mechanisms that may underpin the comorbidity between ADHD and pain sensitization. A mild and sustained pro-inflammatory environment in the ACC and PI drives changes in synaptic-related (long-term potentiation, axon guidance, outgrowth of neuronal components) and apoptotic processes. These impairments alter cell-cell connectivity and neuronal activity, thus participating in ADHD and chronic pain pathogenesis.
Cognitive effort, efficient coding and non invasive fMRI measurement of their relation in sensori-motor responses
by Simon BOYLAN (Institut de neurosciences cognitives et intégratives d'Aquitaine)
The defense will take place at 14h00 - Amphitéatre Bâtiment Bordeaux Biologie Santé, 2 rue Dr Hoffmann Martinot, 33000 BORDEAUX
in front of the jury composed of
- Alexandre ZENON - Directeur de recherche - Université de Bordeaux - Directeur de these
- María Asunción FERNáNDEZ SEARA - Professeure - Department of Radiology Clinica Universidad de Navarra Pamplona (Spain), Adjunct Associate Professor of Radiology University of Pennsylvania - Rapporteur
- Julie DUQUé - Professeure des universités - Université catholique Louvain - Rapporteur
- Matthew CHALK - Enseignant-Chercheur (ENAC, ISAE) - Institut de la vision - Examinateur
- Emmanuel BARBIER - Directeur de recherche - Grenoble Institut des Neurosciences - Examinateur
- Gaël JOBARD - Maître de conférences - Institut des Maladies Neurodégénératives CNRS UMR 5293 - Examinateur
Cognitive effort is a ubiquitous subjective feeling of exertion that pushes people to avoid demanding tasks. From a biological and evolutionary point of view, mental effort is thought to be a mechanism intended to preserve cognitive resources. However, so far, no consensus on the nature of these resources has been established. Since the brain functions as an information-processing organ, efficient coding theory suggests that cognitive resources—whatever their nature—are optimized and should depend on information gain. This hypothesis assumes certain principles about neural coding and information processing. Firstly, we frame our work in the premise that the brain is a Bayesian information-processing machine, that updates internal models through inferences between inputs and previous beliefs. If stimuli are familiar and naturalistic, efficient neural coding can take place to optimize information coding and processing. If these conditions are met, then we can estimate the quantity of information computed by the brain as the relative entropy between prior and posterior beliefs, or information gain; moreover the quantity of energy needed to compute information being optimized, energy spent on a task should be proportional to this same quantity. Indirect measures of this relationship have been validated through pupillometry, as pupil size correlates with information rate during cognitive tasks. In this thesis, we designed experiments to further validate this information-theoretical framework, using complementary behavioral and neuroimaging measures. To assess this hypothesis, we conducted three key experiments : two joystick visuo-motor and oculomotor tracking tasks with pupillometry, and a response-to-stimulus (Hick-Hyman) task in fMRI. The first study investigates the relation between cognitive effort, pupil size and continuous visual-motor prediction under this information framework. By controlling information components of the target, such as predictability, lag, speed and acceleration, we can validate the information origin of cognitive effort (NASA-TLX) and its correlation with pupil size . The second experiment was developed to test the overnight memorization and implicitness of eye and hand continuous tracking. Using the same design as in the first experiment, we ran four experimental sessions, divided in joystick and eye tracking, on two consecutive days. We showed that participants implicitly learned to better predict repeating parts of the trajectory, which resulted in better performance and smaller pupil dilation. The last study was designed to investigate the relationship between information processing and energy dissipation in the brain by quantifying the cerebral metabolic rate of oxygen (CMRO2) during a response to stimulus task in fMRI (BOLD-ASL sequence). Hick-Hyman task maps a different number of stimuli to their response buttons, depending on the complexity (entropy) of the trial or block. As a linear relationship exists between the quantity of information processed (entropy) and the performance (response time) during the task, we hypothesized that there should be a similar relation between the quantity of information needed to accomplish a task and the energy allocated to do so. We addressed multiple technical issues related to CMRO2 computation in a cognitive task context. While we have improved and automatized the data analysis pipeline, we faced significant challenges that prevented us to reach a final conclusion on our initial hypothesis.
LACTATE NEUROPROTECTION IN NEONATAL HYPOXIA-ISCHEMIA
by Ifrah OMAR IBRAHIM (Centre de Résonnance Magnétique des Systèmes Biologiques)
The defense will take place at 9h00 - Salle de conférence Bâtiment BBS Carreire Bâtiment BBS 145 Rue Léo Saignat 33076 Bordeaux
in front of the jury composed of
- Anne-Karine BOUZIER-SORE - Directeur de recherche - Université de Bordeaux - Directeur de these
- Rosa Chiara PAOLICELLI - Professeur associé - Université de Lausanne - Rapporteur
- Laurent SUISSA - Professeur des universités - praticien hospitalier - Université d'Aix Marseille - Rapporteur
- Emilie PACARY - Chargée de recherche - Université de Bordeaux - Examinateur
- Remy GUILLEVIN - Professeur des universités - praticien hospitalier - Université de Poitiers - Examinateur
Since the introduction of the astrocyte-neuron lactate shuttle (ANLS) concept by Pellerin and Magistretti in 1994, it has been proposed that lactate produced by astrocytes via glycolysis is transferred to neurons as a preferred energy substrate. More recently, the critical role of ANLS in brain activation and its associated functions has been demonstrated in vivo. Given that lactate is essential for neuronal activity, the question arises: could it also be neuroprotective in conditions characterized by cerebral energy deficits? To address this question, we used a neonatal hypoxia-ischemia (NHI) model, a leading cause of mortality and subsequent disabilities in infants. NHI results in brain lesions due to a significant reduction in oxygen (O2) and glucose supply. Currently, the only clinical treatment is moderate therapeutic hypothermia (TH), which helps limit the neurological damage caused by NHI. However, nearly half of the affected newborns do not respond favorably to this treatment. Research conducted by our team using an NHI rat model demonstrated that lactate administration has neuroprotective effects. The aim of my thesis was to determine whether lactate administration is compatible with HT following an NHI event and to compare the effects of combining these two therapies with HT alone. To achieve this goal, my thesis was structured around three main objectives: 1. Development of a hypothermia protocol in an NHI rat model: This was done to identify optimal treatment conditions. Three hypothermia durations (2 h, 3 h, and 5 h) post-NHI were compared through longitudinal monitoring of brain damage using MRI (Bruker 4.7T) and various behavioral tests. Histological and immunohistochemical analysis were also conducted to provide complementary insights. 2. Evaluation of the therapeutic potential of lactate combined with hypothermia: The neuroprotective effects of this combination were compared to TH alone. The optimal window for lactate administration was also established. The molecular mechanisms underlying these neuroprotective effects were investigated using Western blot analysis. Additionally, the impact of lactate on neuroinflammation was examined by evaluating its role in modulating microglial phenotypes in vitro. 3. Assessment of the safety of lactate administration on neonatal blood parameters: This was conducted through a retrospective study of preterm infants who received sodium L-lactate infusions. Our findings clearly indicated that 2 hours of TH were sufficient to reduce brain lesion volumes and achieve optimal performance in behavioral tests. Moreover, lactate administration combined with TH proved to be more neuroprotective than TH alone. Finally, in the retrospective study, sodium L-lactate infusion in preterm infants did not increase lactatemia or disturb other blood parameters. In conclusion, lactate administration is neuroprotective in the context of NHI, even when combined with TH, and is safe for preterm infants, even when lactatemia is already elevated. These results suggest promising potential for clinical pediatric applications.
ED Sciences Physiques et de l'Ingénieur
Two-phase flow liquid-gas in a rough contact for high performance metal seals applications.
by Christian KANKOLONGO (I2M - Institut de Mécanique et d'Ingénierie de Bordeaux)
The defense will take place at 10h00 - ENSAM ENSAM Esplanade des Arts et Métiers 33405 TALENCE
in front of the jury composed of
- Didier LASSEUX - Directeur de recherche - CNRS Talence - Directeur de these
- Marc PRAT - Directeur de recherche émérite - CNRS Toulouse - CoDirecteur de these
- Anne-Laure BIANCE - Directrice de recherche - Institut Lumière Matière - Examinateur
- Cyprien SOULAINE - Chargé de recherche - CNRS Orléans - Rapporteur
- Hugues BODIGUEL - Professeur - Grenoble INP - Rapporteur
Mechanical assemblies, used for example in the primary circuit of a nuclear power plant, generally consist of two flanges made of hard metallic material and a gasket made of soft metallic material. The flanges have surface defects due to the manufacturing process (e.g., turning process) which create multi-scale interfaces, thus forming a leakage path after being brought into contact by a clamping force. Currently, the sealing performance of an assembly is characterized by a gas test (typically helium) even if the assembly is intended to seal liquid. Hence, it is challenging to justify liquid tightness solely based on gas tightness knowledge. Optimizing the sealing of gaskets involves mastering contact mechanics and understanding fluid flows that exhibit specific behaviors through multi-scale interfaces (capillarity, liquid film flow, ...). The objective of this thesis work is to establish numerical models to study liquid leakage under two-phase flow conditions, primarily imbibition, i.e., when the mechanically dry air-saturated contact is invaded by a wetting liquid. In this modeling, the flow in a gasket's leakage path is modeled as in a channel with a triangular cross-section, taking into account the effects of capillarity and liquid film flows developing in sharp corners. The results from these numerical models are then compared with experimental measurements. The analysis shows that the more significant the flows in the sharp corners, the more the liquid invasion throughout the channel is disturbed.
ED Sciences et environnements
Is sulphur fertilization an effective lever to limit the soil-to-grain transfer of cadmium in durum wheat?
by Agathe VIDAL (ISPA - Interaction Sol-Plante-Atmosphère)
The defense will take place at 14h00 - Salle de réunion centre - ISPA UMR ISPA - Bâtiment C1 71 avenue Edouard Boulaux 33882 Villenave d'Ornon
in front of the jury composed of
- Matthias WIGGENHAUSER - Senior scientist - ETH Zurich - Examinateur
- Catherine SIRGUEY - Maître de conférences - Université de Lorraine - LSE - Examinateur
- Camille DUMAT - Professeur des universités - Toulouse INP-ENSAT - Rapporteur
- Christophe SALON - Directeur de recherche - INRAE - Rapporteur
Cadmium (Cd) is a non-essential and highly toxic metal, generally occurring at trace level in soils. Its origins are natural, linked to pedogenesis, but also anthropogenic (contamination by agricultural inputs, industrial wastes, etc.). By taking up Cd from the soil through their roots, plants accumulate this contaminant in their aboveground parts, threatening the food safety. This is the case for durum wheat, which is the cereal that accumulates the most Cd in its grains, and therefore is a strong contributor to the chronic dietary exposure of the French population to Cd. Cd is carcinogenic and highly toxic to humans especially for kidneys and therefore, the European Union has established regulatory limits setting maximum levels of Cd in numerous foodstuffs. As a result of recent toxicological studies, numerous new regulatory limits have been established and existing ones have been decreased. For durum wheat grain, the limit has recently been revised downwards from 0.20 mg Cd kg-1 to 0.18 mg Cd kg-1 (EC 915/2023). Further decreases are expected in the future, pointing out the need to find solutions to limit the transfer of Cd from soil to grain. Cd has a strong affinity for sulfur (S), with which it forms complexes that are highly stable with the thiol (-SH) groups of organic molecules, and more labile with sulfates. The literature shows that the addition of S to soil can modify not only the phytoavailability of this metal in soil but also its distribution between plant organs. Cd-S ligand complexes are known to detoxify this metal by sequestration in vacuoles, particularly in roots. However, literature mainly concerns polluted soils and phytoextraction, with little work on weakly contaminated agricultural soils. The aim of this thesis work was to test whether the addition of S at doses and chemical forms used in cereal cultures could limit Cd accumulation in durum wheat grains in the context of agricultural soils. We showed, under controlled conditions, that the solubility of Cd can be increased by the addition of ammonium sulfate, not by the direct effects of sulphates, but by the acidification resulting from the nitrification of ammonium. In hydroponics and in the field, the addition of S slightly reduced the Cd concentration in durum wheat grains, sometimes in association with greater retention of Cd in roots, as expected. We observed that most of the Cd was stored in the roots and that, during the grain filling, it was remobilized and transferred to the aboveground parts concomitantly with S. By reducing the remobilization of S from the roots, sulfur fertilization could then help to also limit the remobilization of Cd from the roots to the grain. Besides, our results showed that S fertilization could also affect the distribution of biomass between organs, thus affecting their Cd content. Overall, our work suggests that in durum wheat, ensuring that the S requirements of the plant are met could slightly reduce the Cd content of the grain through indirect effects on biomass and possibly through direct S-Cd interaction mechanisms. Even if its effect is not very strong, it is worth considering S fertilization as a lever to reduce cadmium contamination in durum wheat.
ED Sociétés, Politique, Santé Publique
Childhood Emerald Green: Anthropological approach to child health and mediation in the context of pluralism of relationships to care in the Uitoto community (Amazonia)
by Adriana Marcela BENAVIDES OCAMPO (Passages)
The defense will take place at 13h30 - Salle Denucé 3ter Pl. de la Victoire, 33000 Bordeaux
in front of the jury composed of
- Rita NEVES - Professeure des universités - Département d'anthropologie, Université Fédérale du Rio Grande Do Norte - Rapporteur
- Catherine ALES - Directrice de recherche émérite - CNRS – EHESS, CéSor - Examinateur
- Fiona GEDEON ACHI - Maîtresse de conférences - ISPED/ Bordeaux Population Health, Université de Bordeaux - Examinateur
- Guillaume ODONNE - Directeur de recherche - Directeur de recherche CNRS – LEEISA - Rapporteur
The Uitoto, an indigenous community in the Colombian Amazon at the heart of the ethnography proposed in this thesis, present a state of health which, as in other indigenous communities in South America, is marked by the persistence of infectious and parasitic diseases, and higher maternal and infant mortality rates than in the rest of the population of the countries in which these communities live. Based on this situation, since 2014 I have been working with Uitoto communities living in Amazonas, first as an epidemiologist and then as part of my anthropology training, to highlight and analyse the ways in which the Uitoto think about their relationship with the body, health, disease and healthcare, by including them in their cosmovision. As a corollary, the thesis documents the salient elements that have marked the collective history of the Uitoto, their cultural identity and their relationship with their environment, the forest and the river, all of which point to the central notion of balance that marks the material and spiritual life of the Uitoto, as well as their prevention and care practices. The thesis describes the decisive role of the shaman and discusses how ethnomedicine and biomedicine can come together to co-construct care in a country where pluralism of identity has been recognised in the national constitution since 1991. The thesis also discusses, in an applied dimension, the conditions for mediation between ethno and biomedicine and the way in which it could take shape in this context, in order to imagine more ‘ welcoming' care relationships towards different types of knowledge.
Integration and secondary use of heterogeneous hospital health data: from local uses to federated analysis
by Romain GRIFFIER (Bordeaux Population Health Research Center)
The defense will take place at 14h00 - ISPED - Amphithéatre Louis Université de Bordeaux - Campus Carreire 146 Rue Léo Saignat, 33000 Bordeaux
in front of the jury composed of
- Fleur MOUGIN - Professeure des universités - Université de Bordeaux - Directeur de these
- Bastien RANCE - Maître de conférences - praticien hospitalier - Hôpital Européen Georges Pompidou AP-HP - Rapporteur
- Leslie GRAMMATICO-GUILLON - Professeur des universités - praticien hospitalier - CHRU de Tours - Rapporteur
- Vianney JOUHET - Praticien hospitalier - CHU de Bordeaux - CoDirecteur de these
- Rodolphe THIEBAUT - Professeur des universités - praticien hospitalier - Université de Bordeaux - Examinateur
- Pascal STACCINI - Professeur des universités - praticien hospitalier - Université Côte d'Azur - Examinateur
Healthcare data can be used for purposes other than those for which it was initially collected: this is the secondary use of health data. In the hospital context, to overcome the obstacles to secondary use of healthcaree data (data and organizational barriers), a classic strategy is to set up Clinical Data Warehouses (CDWs). This thesis describes three contributions to the Bordeaux University Hospital's CDW. Firstly, an instance-based, privacy-preserving, method for mapping numerical biology data elements is presented, with an F-measure of umprint{0.850}, making it possible to reduce the semantic heterogeneity of data. Next, an adaptation of the i2b2 clinical data integration model is proposed to enable CDW data persistence in a NoSQL database, Elasticsearch. This implementation has been evaluated on the Bordeaux University Hospital's CDW, showing improved performance in terms of storage and query time, compared with a relational database. Finally, the Bordeaux University Hospital's CDW environment is presented, with the description of a first CDW dedicated to local uses that can be used autonomously by end users (i2b2), and a second CDW dedicated to federated networks (OMOP) enabling participation in the DARWIN-EU federated network.
Shedding light on the ways in which neo-titular teachers talk about and think about professional action through a longitudinal accompanying research project
by Virginie BILLON (Laboratoire d'épistémologie et didactiques disciplinaires, professionnelle et comparée de Bordeaux)
The defense will take place at 14h00 - Amphithéâtre Averroès INSPE de Bordeaux Caudéran Bâtiment 5- 2ème étage 49, rue de l'Ecole Normale 33200 BORDEAUX
in front of the jury composed of
- Martine JAUBERT - Professeure émérite - Université de Bordeaux, INSPE de l'académie de Bordeaux - Directeur de these
- Dominique BROUSSAL - Professeur des universités - Université Toulouse Jean Jaurès - Rapporteur
- Sandrine AEBY-DAGHE - Professeure des universités - Université de Genève Faculté de psychologie et des sciences de l'éducation - Rapporteur
- Claudine GARCIA-DEBANC - Professeure émérite - Université Toulouse 2 Jean Jaurès - Examinateur
- Stéphanie VOLTEAU - Maîtresse de conférences - Université de Poitiers, INSPE de l'académie de Poitiers, FoReLLIS Unité de Recherche 15076 - Examinateur
The aim of our research, which is essentially comprehensive, is to describe certain features of the professional development of novice teachers during the course of a mentoring scheme. It is interested in what discursive movements reveal during language interactions between peers and between peers and researchers, interactions centred on elements of their practice as well as on the theory/practice links. In our study, the analysis of practice is based on a didactic scenario relating to an independent writing workshop. The theoretical dimensions mobilised by the participants relate to the multiagenda model (Bucheton, Soulé, 2009) and the notion of gesture (professional, didactic, adjustment, study and learning). Ultimately, our results should provide input for teacher training schemes, by linking analysis of practice to contributions from disciplinary and professional didactics.
THe political mobilization of the European Peripheries: The transformations of the centre-periphery cleavage in the Basque Country and Scotland (2007-2017)
by Luis EMALDI AZKUE (Centre Emile Durkheim)
The defense will take place at 14h00 - Salle Copernic Sciences Po Bordeaux 11 allée Ausone | Domaine universitaire 33607 Pessac Cedex
in front of the jury composed of
- Xabier ITCAINA - Directeur de recherche - CNRS - Sciences Po Bordeaux - Université de Bordeaux - Directeur de these
- Vincent TIBERJ - Professeur des universités - Sciences Po Bordeaux - Examinateur
- Michael KEATING - Professeur émérite - University of Aberdeen - Rapporteur
- Igor AHEDO - Associate Professor - Université du Pays Basque - Examinateur
- Emilie VAN HAUTE - Professeure - Université Libre de Bruxelles - Examinateur
- Sonia ALONSO - Associate Professor - Universidad de Deusto - Rapporteur
Since the financial crash of 2008, the economic crisis has become a political crisis in many European countries, transforming the partisan systems that have shaped politics for decades. New political parties have emerged, some inspired by the social movements in southern Europe in 2011, and older ones are enjoying renewed success, transforming politics. Some studies point to the emergence of one or more new cleavages linked to globalization. On the other hand, long-standing center-periphery conflicts have lost none of their topicality and, on the contrary, are enjoying renewed momentum, as illustrated by the referendum for Scottish independence in 2014 or Catalonia in 2017. How, then, are we to understand the rise of these ethnoregionalist phenomena in this changing context, where the contours of the cleavages that structure partisan systems are being redefined? To what extent do these cleavages intersect or intertwine, and how? The aim of this research project is therefore to analyse the transformations of the Center-Periphery cleavage in relation to these new emerging issues, using a multidimensional approach. The method combines quantitative and qualitative approaches, studying political parties and their organizations, their ideological positioning on the basis of electoral platforms, and finally, their socio-structural bases. The cases of the Basque Country and Scotland will be studied in greater detail. The central thesis is that the center-periphery cleavage has undergone transformations in form and content, crystallized during the Neoliberal Critical Juncture. The socio-structural bases of electorates are shifting with the phenomena of re-alignments; the stakes around these ethno-regionalist demands go beyond the national question understood in the XIX/XXth century sense and are articulated with contemporary political issues (European integration, austerity, welfare, ecology...); and new forms of political party organization are being put in place to meet the challenges posed by new forms of engagement and participation.