ED Mathématiques et Informatique
Improving the clinical follow-up of certain intracranial tumors by using differential equations and learning methods
by Virginie MONTALIBET (IMB - Institut de Mathématiques de Bordeaux)
The defense will take place at 10h00 - Salle de conférence Institut de Mathématiques de Bordeaux, 351 Cours de la Libération, Bât A33, 33405 Talence.
in front of the jury composed of
- Olivier SAUT - Directeur de recherche - CNRS - Directeur de these
- François ROUSSEAU - Professeur des universités - IMT Atlantique - Rapporteur
- Sébastien BENZEKRY - Chargé de recherche - Centre Inria d'Université Côte d'Azur - Rapporteur
- Irene BALELLI - Chargée de recherche - Centre Inria d'Université Côte d'Azur - Examinateur
- Nicolas PAPADAKIS - Directeur de recherche - CNRS - Examinateur
- Annabelle COLLIN - Professeure des universités - Université de Bordeaux - CoDirecteur de these
- Aïna VENKATASAMY - Médecin chercheur - Centre d'imagerie médicale GIE de l'IHU de Strasbourg, Laboratoire ICUBE, équipe MIMESIS de Stéphane Cotin - Examinateur
Meningiomas are among the most common benign tumors of the central nervous system. Less dangerous than malignant tumors, clinicians generally opt for a regular clinical follow-up rather than treatment or surgery that may be more dangerous than the presence of the meningioma. In this work, in close collaboration with the clinic, we aim to study each stage of patient follow-up to assist surgeons in their decision-making. The first phase, which is necessary to the subsequent ones, involves acquiring MRI images to identify and segment tumors. Here, we consider the application of deep learning algorithms to automate this segmentation, which is currently performed by clinicians. A cohort of 319 patients, along with their images and segmentation masks, will be used for this purpose. An initial analysis will reveal promising results for the identification and segmentation of meningiomas within the cohort. We will compare the architecture used with other models and previous work in the literature. Once the tumor has been segmented and diagnosed, the patient is generally followed up regularly. At each consultation, the doctor takes new images to monitor the tumor's evolution over time and to build up a cohort of longitudinal data. The clinician must then answer questions such as: should surgery be considered, or should follow-up continue? A better understanding of meningioma growth would help guide the surgeon's decision. To this end, we will study and compare different mathematical models based on ordinary differential equations (ODE), able to modeling tumor growth. Various parametric estimation strategies will also be evaluated, primarily in terms of their robustness. In the end, mixed effects and the Gompertz model stand out as providing the best results. Characterized by the decrease of its initial growth rate, the Gompertz model provides additional information. Based on this, and in an attempt to provide patient-specific clinical follow-up, we will try to identify the different phases of this growth, as well as predict the evolution of meningiomas. Mechanistic modeling (ODE) as well as statistical and deep learning methods will be used in this work. Finally, the whole approach will be tested on other tumor types such as schwannomas, or meningiomas induced by hormonal treatments.
ED Sciences Chimiques
Cyclic aromatic nanoribbons
by Luc SOLIMAN (Centre de Recherche Paul Pascal)
The defense will take place at 14h00 - Amphithéâtre 115 Avenue du Dr Albert Schweitzer 33600 Pessac
in front of the jury composed of
- Fabien DUROLA - Chargé de recherche - Université de Bordeaux - Directeur de these
- Agnieszka NOWAK-KROL - Junior Professor - Institut für Anorganische Chemie - Universität Würzburg, Allemagne - Rapporteur
- Jean-Pierre SAUVAGE - Professeur émérite - Université de Strasbourg - Examinateur
- Jean WEISS - Directeur de recherche - Institut de Chimie de Strasbourg - CNRS - Rapporteur
- Cécile ZAKRI - Professeure - Centre de Recherche Paul Pascal - CNRS - Examinateur
The synthesis of conjugated macrocycles from polycyclic aromatic fragments has been a subject of extensive research the last decades because of their unusual structures and physical properties. Our team has developed a synthetic pathway for the formation of new carboxy-substituted polycyclic aromatic compounds based on a modified version of the historical Perkin reaction. This strategy allows the formation of large variety of conjugated molecules, linear or branched, flat or twisted, and has even been proved highly efficient for the formation of macrocyclic compounds. In addition, protection and deprotection techniques allow the controlled assembly of a large number of elements and molecules with increasingly atypical shapes can be designed. Over the last few years, our group reported the synthesis of cyclo-poly-[5]helicenes with persistent figure-of-eight or Möbius band shapes. Despite their geometries similar to twisted cyclic ribbons, these compounds cannot be strictly considered as twisted cyclic nanoribbons due to the remaining single bonds linking the [5]helicene parts. From the existing synthetic strategies, we have designed adapted ones for the formation of fully condensed equivalents of these macrocyclic poly-[5]helicenes, which would then display non trivial topologies of twisted nanoribbons. Herein, we report the different approaches attempted for the synthesis of these novel molecular structures. Using bifunctionalized phenanthrene and naphthalene based building blocks, macrocyclization reactions did not lead to the expected compounds, but instead to macrocycles resulting of [1+1] macrocyclization reactions. These shorter and tense macrocycles were obtained as racemic mixtures of enantiostable products, due to the close proximity between the two orthogonal aromatic parts. The enantiomers were separated by chiral HPLC and their photophysical and chiroptical properties were studied. Further investigations of such phenanthrocyclophane forming reaction led to the synthesis of [1+1] macrocycles incorporating one phenanthrene and one benzene, which are ideal precursors for the photochemical formation of functionnalized coronenes. Other synthetic approaches based on the controlled assembly of the building blocks were explored. By using monoprotected bifunctional building blocks, two complementary flexible precursors can be obtained. The first one is composed of one central phenanthrene substituted by two monoprotected naphthalene units. When deprotected, this flexible precursor can react by Perkin reaction in high dilution conditions with another equivalent of bifunctional phenanthrene to give a flexible precursor for a nanoribbon with a figure-of-eight shape. If this precursor is otherwise engaged with its complementary homologue, composed of a central naphthalene and two monoprotected phenanthrenes, it could lead to the synthesis of a Möbius shaped nanoribbon with three 180° twists.
ED Sciences de la Vie et de la Santé
Neutrophils Extracellular Traps and DNases involvement in COVID-19 physiopathology
by Geoffrey GARCIA (Biologie des maladies cardiovasculaires)
The defense will take place at 14h00 - Salle de conférence Inserm U1034, 1 Avenue Magellan, 33600 Pessac
in front of the jury composed of
- Chloé JAMES - Professeure des universités - praticienne hospitalière - Université de Bordeaux - Directeur de these
- Laurent MACCHI - Professeur des universités - praticien hospitalier - Faculté de Médecine et Pharmacie (Université de Poitiers) - Rapporteur
- David SMADJA - Professeur des universités - praticien hospitalier - Université Paris Cité, Faculté de Santé - Rapporteur
- Emma LEFRANCAIS - Chargée de recherche - - CNRS-Université Toulouse III Paul Sabatier - IPBS UMR5089 - Examinateur
- Vanja SISIRAK - Chargé de recherche - UMR CNRS 5164 – Immunoconcept - Examinateur
During infections, neutrophils release Neutrophil Extracellular Traps (NETs) to capture and kill pathogens. NETs, in coordination with platelets and immune cells, activate coagulation and contribute to immunothrombosis to trap pathogens and prevent their dissemination. They are physiologically degraded by DNases and macrophages. When exacerbated, NETs cause cellular and tissue damage. They are considered central actors in many pathologies, including thrombosis (both arterial and venous) and severe forms of COVID-19. However, the techniques for measuring NETs and DNases are not yet standardized, and the mechanisms underlying the exacerbation of NETosis in COVID-19 are poorly described. We hypothesize that the clinical worsening of patients during COVID-19 is related to an imbalance between NETs and DNases. To address this hypothesis, our objectives are: (1) to define optimal pre-analytical conditions for measuring NET markers; (2) to develop and validate a method for assaying plasma DNase activity; (3) to evaluate the balance between NET markers and DNase activity according to the severity of COVID-19; and (4) to investigate the mechanisms responsible for this NETs/DNases imbalance. Identifying DNase deficiency as an aggravating factor in patients could lead to innovative therapeutic strategies to prevent clinical worsening, such as the administration of DNase.
The embryonic isoform of human RNA polymerase III: its role in tumoral transformation and generation of metastasis
by Elisabeth LATA (Acides nucléiques : Régulations Naturelles et Artificielles)
The defense will take place at 14h00 - Amphithéâtre B Faculté d'odontologie, 146 rue Léo Saignat, 33076 Bordeaux
in front of the jury composed of
- Martin TEICHMANN - Professeur des universités - Université de Bordeaux - Directeur de these
- Julie SOUTOURINA - Directrice de recherche - I2BC - Rapporteur
- Fabienne MEGGETTO - Directrice de recherche - CRCT - Rapporteur
- Giorgio DIECI - Professeur - Università di Parma - Examinateur
RNA polymerase (Pol) III transcribes small non coding RNAs that are essential for the cell. There are two Pol III isoforms containing either RPC7α or RPC7β subunit. RPC7β is ubiquitously expressed whereas RPC7α is only expressed in embryonic stem cells and some tumor cells. Particularly, RPC7α is overexpressed in triple negative breast cancer (TNBC) clinical samples and cell lines. RPC7α deletion in the TNBC cell line MDA-MB-231 reduces tumor growth and metastases formation in a xenograft mouse model. However, the molecular mechanisms by which Pol IIIα regulates tumorigenesis and metastasis are still unknown. In this thesis, I show that the suppression of RPC7α in MDA-MB-231 cells alters the expression of several messenger RNAs, some of which are involved in the regulation of cancer and gene expression. Analysis of RPC7α localization indicates that, in addition to occupying Pol III genes, RPC7α also colocalizes with Pol II on coding genes. These genes are among the most highly expressed in MDA-MB-231 cells and are involved in important mechanisms for tumors and metastasis such as translation and cell interaction with the extracellular matrix. Unlike RPC7α, RPC7β is only localized on Pol III genes. Thus, these results suggest that RPC7α acts directly with Pol II on coding genes, possibly to promote their expression, which would explain its important role in tumor growth and metastasis generation in TNBC.
ED Sciences Physiques et de l'Ingénieur
Fundamental optical properties of single semiconductor nanocrystals at cryogenic temperatures.
by Elise PRIN (Laboratoire Photonique, Numérique & Nanosciences)
The defense will take place at 14h00 - Amphithéâtre (E100) Institut d'Optique d'Aquitaine, 1 Rue François Mitterrand, 33400 Talence
in front of the jury composed of
- Philippe TAMARAT - Professeur - Université de Bordeaux - Directeur de these
- Carole DIEDERICHS - Maîtresse de conférences - Sorbonne Université - Rapporteur
- Maria CHAMARRO - Professeure - Sorbonne université - Rapporteur
- Jean-Pierre HERMIER - Professeur - Université Versailles St-Quentin-en-Yvelines - Examinateur
- Jérome CAYSSOL - Professeur - Université de Bordeaux - Examinateur
- Brahim LOUNIS - Professeur - Université de Bordeaux - CoDirecteur de these
Semiconductor nanocrystals exhibit outstanding optical and electronic properties due to the quantum confinement of their charge carriers, making them valuable for various applications in optoelectronics, light-emitting devices, and spin-based technologies. Understanding the physics of the band-edge exciton, whose recombination is at the origin of their photoluminescence, is crucial for developing these applications. This thesis focuses on the experimental study of the optical properties of indium phosphide and lead halide perovskites nanocrystals. Using magneto-photoluminescence spectroscopy on single nanocrystals at low temperatures, we reveal spectral fingerprints highly sensitive to nanocrystal morphologies and elucidate the entire band-edge exciton fine structure and charge-complex binding energies. In InP/ZnS/ZnSe nanocrystals, the evolution of photoluminescence spectra and decays under magnetic fields show evidence for a ground dark exciton level lying less than a millielectronvolt below the bright exciton triplet, findings supported by a model accounting for the shape anisotropy of the InP core. In lead halide perovskites, we demonstrate that the ground exciton state is dark and lies several millielectronvolts below the lowest bright exciton sublevels, settling the debate on the bright-dark exciton level ordering in these materials. Combining our results with spectroscopic measurements on various perovskite nanocrystal compounds, we establish universal scaling laws relating exciton fine structure splitting, trion and biexciton binding energies to the band-edge exciton energy in lead-halide perovskite nanostructures, regardless of their chemical composition. Lastly, preliminary spectroscopy analyses on perovskite nanorods with a high aspect ratio suggest their potential as candidates for quantum light emitters due to their characteristic single emission line.
ED Sociétés, Politique, Santé Publique
Development and evaluation of AI-based personalization algorithms for attention training.
by Maxime ADOLPHE (Bordeaux Population Health Research Center)
The defense will take place at 14h00 - Salle Ada Lovelace INRIA 200 Av. de la Vieille Tour, 33405 Talence
in front of the jury composed of
- Hélène SAUZEON - Professeure - Université de Bordeaux - Directeur de these
- Julien DIARD - Chargé de recherche - Laboratoire de Psychologie et Neurocognition - Rapporteur
- Pierre-Yves OUDEYER - Directeur de recherche - INRIA centre de l'université de Bordeaux - CoDirecteur de these
- Walter BOOT - Professeur - Center on Aging and Behavioral Research Division of Geriatrics and Palliative Medicine Weill Cornell Medicine - Rapporteur
- Vanda LUENGO - Professeure - Sorbonne Université - LIP6 - Examinateur
- Claudia VON BASTIAN - Associate Professor - University of Sheffield - Examinateur
Intelligent Tutoring Systems (ITS) offer innovative educational solutions by providing personalized learning experiences that adapt to individual variability. This adaptability is crucial for tailoring curricula to maximize student engagement and learning outcomes. The Flowers team (INRIA Bordeaux) has developed an ITS based on the Learning Progress Hypothesis (LP-H). The LP-H suggests that individuals are intrinsically motivated to engage in learning activities when they perceive their own progress. This perception of progress acts as an internal motivator, encouraging them to pursue more activities where they can continue to make significant progress. The system, named Zone of Proximal Development and Empirical Success (ZPDES), uses a machine learning algorithm to customize learning trajectories by dynamically identifying and exploiting activities that yield maximal learning progress, thereby enhancing student motivation. The study of cognitive Training (CT), which involves structured tasks designed to improve specific cognitive functions such as memory, attention, and problem-solving, reveals that the benefits of CT are highly sensitive to inter-individual differences, highlighting the need for CT personalization. In this context, our research explores the potential of applying the ZPDES framework to CT to improve cognitive performance, engagement, and motivation. We first conducted a systematic review to identify current strategies for individualizing cognitive training. The review revealed the field's relative immaturity, characterized by a limited number of studies (n=12), methodological issues, and a wide variety of approaches within this small sample. Then, through a subjective review, we examined the Multi-Object Tracking (MOT) task and documented its effectiveness as CT and its dependence on manipulated task parameters. In individuals varying in age and neurodiversity, we observed near transfer effects, such as improvements in attention-related tasks (e.g., the Useful Field of View task), far transfer effects (e.g., working memory and executive functions), and ecological transfers, including better perception of biological movements and soccer performance. Based on these insights, we designed and tested an individualized CT program using the MOT task. First, we developed a comprehensive cognitive battery comprising seven tasks covering attention, working memory and executive functions. Then, two experiments were carried out: one with young adults (n=72) and the other with older adults (n=50), each time with a control group (non-personalized CT) and an experimental group (personalized/ZPDES CT). Participants completed three hours of pre- and post-assessment, and the CT lasted eight hours (spread over 2 weeks), managing their schedules autonomously via an online platform. The results showed that ZPDES could be more effective than a control condition, with improved performance on trained tasks in both studies, underlining the benefits of individualized training paths. However, motivation and engagement were lower in the groups using ZPDES, probably due to cognitive load and metacognitive factors. Overall, individualizing cognitive training through systems like ZPDES provides a promising direction for future research by providing automatic methods for taking individual differences into account in CT programs while respecting methodological standards for evaluating the effectiveness of CT. As a result, our work contributes to the growing body of knowledge in both ITS and CT domains while stressing the crucial role of challenges related to motivation and engagement to optimize the effectiveness of these individualized approaches for cognitive and educational outcomes.