ED Mathématiques et Informatique
Machine learning and network science to prevent online fraud
by Aurélien FACCI (LaBRI - Laboratoire Bordelais de Recherche en Informatique)
The defense will take place at 14h00 - Amphithéâtre Université de Bordeaux, LaBRI, Bât. A30, 351 cours de la Libération 33405 Talence cedex
in front of the jury composed of
- Bruno PINAUD - Professeur des universités - Université de Bordeaux - Directeur de these
- Hamida SEBA - Professeure des universités - Université Lyon 1 - Rapporteur
- Mustapha LEBBAH - Professeur des universités - UVSQ - Rapporteur
- Serge CHAUMETTE - Professeur des universités - Université de Bordeaux - Examinateur
Every day, BNP Paribas Personal Finance (BNPP PF) receives thousands of instalment-payment applications, processed within seconds. This speed defines the quality of the service, but also its vulnerability: fraudsters exploit it to obtain financing with no intention of repaying. To detect them, BNPP PF links applications in a graph, where each one becomes a node connected to those sharing identifying information. This relational structure holds a wealth of information that remains largely untapped. This thesis shows how to leverage it for better fraud detection, under the real-time constraints of the service. This thesis makes three contributions. First, a multi-level identity resolution that reveals links between applications, including a method suited to instalment payment. Second, a hybrid architecture coupling graph neural networks with ensemble methods, to exploit both individual and relational signals. Third, the release of an anonymised and distorted dataset, derived from real-world data. The results confirm the contribution of the graph and of the hybrid coupling, whose benefit grows when relational information is scarce in the data.
ED Sciences de la Vie et de la Santé
Development of photoactivable polymersomes for temporal et spatial control of molecular delivery into the brain
by Camille RUFFIER (Nutrition et Neurobiologie Intégrée)
The defense will take place at 14h00 - Salle de conférence CARF Bâtiment CARF 146, rue Léo Saignat, 33076 Bordeaux cedex
in front of the jury composed of
- Clémentine BOSCH-BOUJU - Maîtresse de conférences - Nutrineuro, UMR 1286, Univeristé de Bordeaux - Directeur de these
- Laurent VENANCE - Directeur de recherche - Centre interdisciplinaire de recherche en biologie (CIRB), CNRS UMR 7241, Inserm U1050, Collège de France - Rapporteur
- Simona MURA - Professeure des universités - Institut Galien Paris-Saclay, UMR CNRS 8612, Université Paris-Saclay - Rapporteur
- Agnès NADJAR - Professeure des universités - Institute of Neurodegenerative Diseases (IMN), CNRS UMR 5293, Université de Bordeaux - Examinateur
- Maxim CAZORLA - Chargé de recherche - Institut de Neurosciences de la Timone - Examinateur
- Angela MUTSCHLER - Maîtresse de conférences - Laboratoire de Chimie des Polymères Organiques (LCPO) - Examinateur
Many neurological and neuropsychiatric diseases remain poorly treated and constitute a major cause of disability worldwide. Several of these pathologies are localized to a specific area of the brain, and their treatment remains inadequate: systemically administered drugs reach the affected areas only in limited concentrations and without precise spatiotemporal control. While the blood-brain barrier and the structural heterogeneity of the brain severely limit the targeted delivery of drugs, alternative approaches such as intracranial pharmacology offer promising prospects. However, these methods remain passive: drug diffusion is neither dose-dependent nor controllable over time, which limits their clinical efficacy. Meanwhile, nanotechnologies offer stable and versatile vectors capable of efficiently encapsulating and transporting various therapeutic agents, but they do not, on their own, allow for localized and on-demand delivery. Our approach addresses these limitations by developing photoactivatable polymersomes capable of releasing their contents in a localized manner under the influence of light. My work is based on three main axes: (i) the design of photoactivable and biocompatible polymersomes; (ii) the evaluation of their safety in order to ensure safe and effective use at the level of brain tissue; (iii) the demonstration of an efficient photorelease of bioactive molecules in neuronal circuits. Our work confirmed that the emulsion-centrifugation process is a suitable method for obtaining a high yield of photoactivable micrometer-sized polymersomes (mean diameter of 8.27 ± 0.14 µm), capable of rapid and localized release of their contents, with a mean release time of 6.39 ± 0.90 s. The biocompatibility and release capacity of these polymersomes were evaluated in vitro on primary murine cortical cultures. Neither illumination at 470 nm (optical fiber Ø 400 µm, NA 0.5, 20 s), nor incubation with polymersomes at increasing concentrations (600 to 9000 polymersomes/well), nor the combination of the two affected cell viability. In vivo tolerance was confirmed by injecting polymersomes into the brains of mice and analyzing glial reactivity by immunolabeling IBA-1 and GFAP proteins 48 hours and 3 weeks post-injection. The polymersomes did not elicit any glial response beyond the effect of the stereotaxic injection itself, demonstrating that the polymersomes and their photoactivation are well tolerated by brain cells and tissues. To demonstrate the efficacy of photorelease in brain tissue and to quantify its ability to modulate neuronal processes, we developed a protocol based on measuring neuronal activity. Electrophysiological recordings were performed on mouse brain sections preserving the synaptic connection between the CA3 and CA1 regions of the hippocampus, a key area involved in memory processes. Thanks to the encapsulation and then photorelease of CNQX (100 µM), a competitive antagonist of AMPA/kainate receptors, we have demonstrated that polymersomes act as on-demand reservoirs, allowing prolonged and localized drug administration around the injection site. In conclusion, photoactivable polymersomes represent a promising tool for studying brain mechanisms and developing innovative therapeutic strategies. Their potential is currently being evaluated in vivo in a murine model of glioblastoma for the targeted release of CNQX to limit tumor invasion.
OLFACTION AND OXYTOCIN IN FEMALE ALLOPARENTAL BEHAVIORS
by Tessa SCARABELLO (Institut Interdisciplinaire de Neurosciences)
The defense will take place at 14h30 - Amphi Broca Centre Broca Nouvelle Aquitaine 146 Rue Léo Saignat, 33000 Bordeaux
in front of the jury composed of
- Lisa ROUX - Directrice de recherche - Université de Bordeaux - Directeur de these
- Françoise MUSCATELLI - Directrice de recherche - Institut de Neurobiologie de la Méditerranée - Examinateur
- Ioana CARCEA - Assistant professor - Rutgers Brain Health Institute - Rapporteur
- Nathalie BUONVISO - Directrice de recherche - Centre de Recherche en Neurosciences de Lyon - Rapporteur
- Nicolas RENIER - Directeur de recherche - Institut du cerveau - Examinateur
Alloparental behaviors define the set of actions undertaken by adults to insure the survival of other individuals' progeny such as crouching over the young, retrieval, or parental nesting. The very first encounter with a pup can trigger the emergence of these behaviors in naive virgin mice who had never expressed these behaviors before, and their performances is known to improve upon repeated exposures to pups. Yet, the neurobiological substrates of this phenomenon are still unclear. Previous work highlighted the importance of auditory cues and oxytocin (OT) release in the auditory cortex of virgin females for the establishment of retrieval behavior. In contrast, the role played by olfaction in the transition of mice from naive to efficient caretakers remains so far little explored. The goal of this work has been to assess the impact of olfaction in the establishment of alloparental behaviors in naive female mice, as well as the influence of oxytocinergic neuromodulation in the main part of the olfactory cortex, the piriform cortex (PIR). We found that within just a few minutes, naive C57Bl6/J female mice exposed to pups start building a nest to host the pup. However, when the odor of the pup is masked, the onset of nesting in these mice is delayed despite comparable pup investigation times compared to controls. In addition, mice display non-adapted behaviors when they are unable to smell the natural odor of the pup: they favor failed pup retrievals over nest building. Altogether, these first observations suggest that olfaction plays a role in triggering adapted alloparental behaviors upon first pup exposure. Given the role of OT in social behaviors, we hypothesized that oxytocinergic transmission in the PIR could play a role in alloparental behavior emergence. Using immunochemistry in the Oxtr-3xHA-T2A-iCreERT2 mouse line, we showed that oxytocin receptors (OTR) are mostly expressed in the deep layer 3 of the PIR, unlike in previous works based on OTR-targeted antibodies. To assess the dynamics of OT signaling in the PIR during our task, and in particular during pup olfactory investigation preceding the start of nesting, we monitored mice with fiber photometry using an OT GRAB sensor expressed in the PIR. This method did not reveal any significant OT level change at the time of pup investigation but we found a slow build-up of OT in the PIR spanning the whole task time course. In contrast, using GCaMP8m expressed in OTR-positive cells, we found that OTR-positive neurons are consistently activated across all pup olfactory investigation events, even though they represent only a small percentage of PIR cells. Altogether, these results indicate that OTR and OT are present in the PIR upon pup exposure, and that they could exert a slow influence on neuronal responses in PIR circuits. To selectively suppress the expression of OTR in the PIR and test the impact on pup care strategy, we adopted a viral approach to express the cre-recombinase locally in the PIR of Oxtr[flox] mice. Similar to previous experiments with pup odor masking, this local knock-out of the OTR in the PIR impaired pup care strategy, compared to mice injected with a control virus. To identify the brain-wide circuits involved in this behavioral effect, we used brain-wide activity mapping combined with brain clearing (iDISCO) to compare the brains of naive females exposed for the first time to a pup, with or without a local knock-out of OTR in the PIR. We found striking differences in the activation of the Orbito Frontal Cortex, a region known to participate to sensory processing and decision-making in social contexts. These results suggest that OT in the PIR contributes to gate the neuronal circuits recruited during pup odor exposure, leading to the selection of appropriate behaviors. Altogether, this work paves the way for future research to understand how olfaction and its modulation by OT shapes pup-directed behavioral changes in naive female mice.