Дисертації з теми "Maladies neurodégénératives – Modèles mathématiques"
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Haffaf, Hadjer Wafaa. "Analyse de l'agrégation des protéines dans les maladies neurodégénératives amyloïdes : application aux maladies à prion." Thesis, Paris 6, 2014. http://www.theses.fr/2014PA066263/document.
Повний текст джерелаThe amyloid neurodegenerative diseases are characterized by the degeneration and the aggregation of specific proteins. These aggregation processes remain misunderstood by specialists and, mostly, only hypothetical. In this thesis, and in collaboration with biophysicists, we analyze the mechanisms of aggregation, relying on experimental data. Modeling is then a must. We present two models which we compare with the experiments. The first model, well-known from the literature is the Becker-Döring system. An infinite system of ordinary differential equations. This first model allows us to reproduce satisfactorily the early stages of the experiments. The second model we introduce is based on an additional hypothesis which is about the formation of different fibers. This second model allows us to reproduce the experiments
Sivera, Raphaël. "Modélisation et mesure de l'évolution morphologique du cerveau à partir d'IRM structurelles pour l'étude des maladies neurodégénératives." Thesis, Université Côte d'Azur (ComUE), 2019. http://www.theses.fr/2019AZUR4082.
Повний текст джерелаIn medical imaging, the statistical analysis of deformations enables the characterization of the effects of neurodegenerative diseases on the brain morphology. Deformations are able to capture precise changes but their analysis raises specific methodological challenges and the results may be difficult to interpret. The objective of this thesis is to present deformation-based methods and to show applications that contribute towards a better clinical interpretation of morphological changes. In the first part, we introduce a joint model of the effects of normal aging and Alzheimer’s disease on the brain morphology. The model proposes a simple description of both processes and is used to generate realistic and personalized evolutions under several diagnosis conditions. In the second part, a morphometric study is conducted on the MAPT cohort. We bring out an effect of the multidomain intervention on the longitudinal deformation of the brain using multivariate statistics. This effect is not observable using clinical assessments or volumetric measures, but we show that the differences associated with the treatment are correlated with better cognitive performance. The third part extends the statistical methodology used in the second part. A complete hypothesis testing framework for multivariate images is presented. It generalizes existing non-parametric frameworks and requires few hypothesis on the data to be applied. Finally the last part builds on the methodology of the previous sections to explore the relation between morphology and cognition in elderly subjects. The spatial correlations and the patterns of evolution described in this section suggest the existence of several dynamics of evolutions that are associated with specific cognitive changes
Sauty, Benoît. "Multimodal modelling of Alzheimer's Disease progression." Electronic Thesis or Diss., Sorbonne université, 2023. http://www.theses.fr/2023SORUS348.
Повний текст джерелаAlzheimer's disease (AD) is a multi-facet pathology, that can be monitored through a variety of data types. This thesis aims to leverage multimodal longitudinal data, especially imaging scans and cognitive tests, to provide a statistical description of the progression of AD and to enable individual forecasting of future decline. Mixed-effect disease progression models (DPMs) are commonly used for these tasks. In this context, our first contribution questions the frequent assumption that biomarkers follow linear or logistic functions over time, and we propose a geometric framework that assumes the data lie on a manifold and follow geodesics over time. We learn the Riemannian metric of the observation space and are able to model a wider variety of biomarkers, without priors on the shape of the trajectory over time. Using variational auto-encoders, we then extend this framework to neuroimaging data (MRI or PET scans), in order to provide high-dimensional progression models that describe the patterns of structural and functional alterations of the brain over the course of AD. We then apply this family of DPMs to clinical studies data in order to investigate the heterogeneity of AD progression, due to APOE-e4 genotype and sex on patterns of brain alterations. Lastly, we use said DPMs with a set of imaging and fluid biomarkers to identify the specific combinations of input features that best forecast cognitive declines in patients at different stages of the disease. The thesis demonstrates that DPMs can effectively model the progression of AD using a great variety of multimodal longitudinal data and provide valuable insights into the disease's clinical manifestations and progression. These findings can inform clinical trial design and facilitate more accurate prognosis and individualized treatment strategies for patients with AD
Ortholand, Juliette. "Joint modelling of events and repeated observations : an application to the progression of Amyotrophic Lateral Sclerosis." Electronic Thesis or Diss., Sorbonne université, 2024. http://www.theses.fr/2024SORUS227.
Повний текст джерелаProgression heterogeneity in chronic diseases such as Amyotrophic Lateral Sclerosis (ALS) is a significant obstacle to developing effective treatments. Leveraging the growing wealth of large databases through modelling can help better understanding it. However, the data collected only offer access to partial trajectories, that need to be realigned to reconstruct a comprehensive disease progression. To address this challenge, data-driven progression models like the longitudinal Spatiotemporal model were developed. Its main interest is its ability to synchronise patients onto a common disease timeline (temporal aspect) thanks to a latent disease age, while also capturing the remaining variability through parameters that account for outcome ordering (spatial aspect). However, this model was primarily designed for longitudinal data, overlooking crucial outcomes in ALS such as time to death or initiation of life support, like Non-Invasive Ventilation (NIV). Conversely, existing joint models offer the advantage of simultaneously handling longitudinal and survival data. However, they do not realign trajectories, which compromises their temporal resolution. This thesis aimed to expand the Spatiotemporal model into a Joint Spatiotemporal model, enabling, for ALS research, the examination of survival data alongside longitudinal data. First, we applied the Spatiotemporal model to explore how the interaction between sex and onset site (spinal or bulbar) impacts the progression of ALS patients. We selected 1,438 patients from the PRO-ACT database. We demonstrated a significant influence of both sex and onset site on six longitudinal outcomes monitoring the functional and respiratory decline in addition to Body Mass Index. However, this study did not incorporate survival analysis, despite its paramount importance in ALS, due to limitations inherent to the Spatiotemporal model. To address this gap, we associated the Spatiotemporal model with a survival model that estimates a Weibull survival model from its latent disease age, creating a univariate Joint Temporal model. After model validation, we benchmarked our model with a state-of-the-art joint model on PRO-ACT data. Our model exhibited significantly superior performance in terms of absolute bias and mean cumulative AUC for right-censored events. This demonstrated the efficacy of our approach in the context of ALS compared to existing joint models. However, modelling several longitudinal outcomes requires a multivariate approach. Life support initiation that might be censored by death needs to be also considered. We thus extended the Joint Temporal model, into a multivariate Joint Spatiotemporal model with competing risks to analyse NIV initiation. This involved coupling the multivariate Spatiotemporal model with a cause-specific Weibull survival model from the latent disease age. We incorporated spatial parameters with a Cox proportional effect on the hazard. After validation, we benchmarked our model with a state-of-the-art joint model on PRO-ACT data and analysed sex and onset site interaction in complement to the first study. The Joint Spatiotemporal model achieved similar performance to the state-of-the-art model while capturing an underlying shared latent process, the latent disease age, whereas the state-of-the-art models the impact of longitudinal outcomes on survival. To enhance the reproducibility and facilitate the reuse of these models, the proposed models were implemented in the open-source software Leaspy. In conclusion, this thesis introduces the first data-driven progression model combining longitudinal and survival modelling. We demonstrated its relevance to understand the occurrence of critical events in ALS. This work paves the way for further extension to analyse recurrent events, among other potential applications in causal inference
Lenuzza, Natacha. "Modélisation de la réplications des Prions : Implication de la dépendance en taille des agrégats de PrP et de l'hétérogénéité des populations cellulaires." Phd thesis, Ecole Centrale Paris, 2009. http://tel.archives-ouvertes.fr/tel-00453321.
Повний текст джерелаBône, Alexandre. "Learning adapted coordinate systems for the statistical analysis of anatomical shapes. Applications to Alzheimer's disease progression modeling." Electronic Thesis or Diss., Sorbonne université, 2020. http://www.theses.fr/2020SORUS273.
Повний текст джерелаThis thesis aims to build coordinate systems for shapes i.e. finite-dimensional metric spaces where shapes are represented by vectors. The goal of building such coordinate systems is to allow and facilitate the statistical analysis of shape data sets. The end-game motivation of our work is to predict and sub-type Alzheimer’s disease, based in part on knowledge extracted from banks of brain medical images. Even if these data banks are longitudinal, their variability remains mostly due to the large and normal inter-individual variability of the brain. The variability due to the progression of pathological alterations is of much smaller amplitude. The central objective of this thesis is to develop a coordinate system adapted for the statistical analysis of longitudinal shape data sets, able to disentangle these two sources of variability. As shown in the literature, the parallel transport operator can be leveraged to achieve this desired disentanglement, for instance by defining the notion of exp-parallel curves on a manifold. Using this tool on shape spaces comes however with theoretical and computational challenges, tackled in the first part of this thesis. Finally, if shape spaces are commonly equipped with a manifold-like structure in the field of computational anatomy, the underlying classes of diffeomorphisms are however most often largely built and parameterized without taking into account the data at hand. The last major objective of this thesis is to build deformation-based coordinate systems where the parameterization of deformations is adapted to the data set of interest
St-Amour, Isabelle. "Effet des IGIV dans des modèles murins de maladies neurodégénératives." Thesis, Université Laval, 2014. http://www.theses.ulaval.ca/2014/30473/30473.pdf.
Повний текст джерелаIn the search of therapeutic solutions to neurodegenerative diseases, active and passive immunization strategies have been proposed for the clearance of protein aggregates. Intravenous immunoglobulin (IVIg) is a pharmaceutical preparation of over 98% immunoglobulin G prepared from the plasma of thousands of healthy donors. Since natural autoantibodies against pathological proteins have been identified in IVIg, it has been proposed as an alternative to immunotherapy and clinical trials in Alzheimer’s disease (AD) patients are underway. The aim of my PhD project was to evaluate the efficacy, analyze the mechanisms of action of IVIg in animal models of AD and Parkinson’s disease (PD), and identify potential targets for the development of pharmacological alternatives. The bioavailability of IVIg and its ability to reach therapeutic targets in the brain are unknown. In the first part of the project, we quantified the passage of IVIg through the blood-brain barrier (BBB). Our results provide quantitative evidence of BBB transport and brain bioavailability of IVIg in the absence of permeabilization and in sufficient amount to interact with therapeutic targets. In a triple transgenic mouse model of AD (3xTg-AD) that reproduces amyloid and tau pathologies, IVIg injections have improved the cognitive performance and reduced anxiety-like behaviors of treated mice. Despite limited effects on tau pathology, IVIg modulated the central (IL-5/IL-10 ratio) and peripheral (CX3CR1 + and T cells), and reduced the ratio of soluble Aβ42/Aβ40 (-22%) and the concentration of 56 kDa oligomers of Aß (Aß*56) by over 60%. This effect of IVIg on cognition, immunity and Aß pathology suggests that Aβ oligomers, effector T cells and the fractalkine pathway are potential pharmacological targets of IVIg in AD. Finally, we studied the effect of an IVIg treatment in a mouse model of PD. In this model of MPTP intoxication, our results did not demonstrate neurorestorative effects of IVIg on the nigrostriatal system and even suggested adverse effects of IVIg on the dopaminergic system. These preclinical data highlighted the importance of proceeding cautiously in the initiation of clinical trials with IVIg to treat PD patients.
Vallée, Alexandre. "Molecular thermodynamic aspects of dissipative structures in oncology, inflammatory and degenerative processes of Central Nervous System diseases." Thesis, Poitiers, 2017. http://www.theses.fr/2017POIT1409.
Повний текст джерелаEnergy metabolism is the primary determinant of cellular viability. Diseases are the sites of numerous metabolic and energetic production abnormalities. Indeed, the altered cells are derived from exergonic processes and emit heat that flows to the surrounding environment. Many irreversible processes can occur through changing the rate of entropy production. This rate represents a thermodynamic quantity that measures these irreversible processes. Entropy rate is increased by several metabolic and thermodynamics abnormalities in brain tumors, inflammatory processes and neurodegenerative diseases. The research works of this thesis have demonstrated and highlighted the existence of a crosstalk between canonical WNT/beta-catenin pathway and PPAR gamma which plays a major role in the reprogramming of cellular energy metabolism between oxidative phosphorylation, aerobic glycolysis and anaerobic glycolysis, of which the equilibrium point of crosstalk between these molecular pathways varies according to tumor, inflammatory and neurodegenerative diseases. These diseases are dissipative structures, that exchange energy or matter with their environment. They are open systems, far-from the thermodynamic equilibrium that operate under non-linear regime evolving to non-stationary states. Far-from-equilibrium thermodynamics are notions driven by circadian rhythms. Indeed, circadian rhythms directly participate in regulating the crosstalk of the studied molecular pathways. This crosstalk represents an innovative therapeutic target, and molecular data usable for molecular imaging in both positive and differential diagnosis of these diseases
Thomas, Sophie. "PCP4, trisomie 21 et maladies neurodégénératives : construction et étude de modèles murins." Paris 5, 2005. http://www.theses.fr/2005PA05N16S.
Повний текст джерелаPCP4 (PEP-19) belongs to a family of Iq motif proteins involved in calcium transduction signals. It binds calmodulin and regulates CamKII and nNOS wich are involved in neuronal plasticity and wich may also mediate the transduction of apoptotic signal. The gene is localized on HSA21 and is in 3 copies in Down syndrome (DS) patients. To determine whether PCP4 may be involved in some DS phenotypic features, we analysed its expression pattern during mouse development and in the adult brain. PC expression pattern suggests that its overexpression may be involved in some of the DS features such as abnormalities in neuronal differentiation in cluding synaptogenesis and migration. We thus constructed a mouse model of PCP4 overexpression using the ES cells transgenesis method. The transgenicline is currently under study. PCP4 expression in the aging brain has been shown not to vary systematically during normal aging suggesting that PCP4 modulations in human neuropathologies are induced by genes involved in these diseases. Moreover, microarrays analysis suggests that PCP4 modulation is associated with other genes involved in neurotransmission
Dequen, Florence. "Filaments intermédiaires neuronaux et maladies neurodégénératives : caractérisation de nouveaux modèles de souris transgéniques." Thesis, Université Laval, 2009. http://www.theses.ulaval.ca/2009/26415/26415.pdf.
Повний текст джерелаLafon, Pierre-André. "Impact des pesticides sur l'agrégation des amyloïdes dans différents modèles de maladies neurodégénératives." Thesis, Montpellier, 2019. http://www.theses.fr/2019MONTT005.
Повний текст джерелаContamination of the drinking water and agricultural lands by the use of pesticides entering into the food chain is a major environmental and health problem. Epidemiological studies have shown a link between pesticide exposure and Parkinson's disease, but few studies are available on other neurodegenerative disorders. Our hypothesis is that pesticides may be triggering or aggravating factors common to neurodegenerative diseases.In the laboratory, we identified by a screening on the prion protein, PrP, a compound named A6 described for its herbicidal properties. A6 is a derivative of α-terthienyl, a natural molecule extracted from marigolds. A6 compound has the ability to promote oligomeric forms of the prion protein on a prion-infected cell line. My research project aimed to study the effects of the bioherbicide A6 on prion aggregation and propagation in vivo. Mice infected with prions were treated with different doses of this molecule (5, 10 and 20 mg/kg). At the dose of 5 mg/kg, A6 compound decreases the survival time of animals with an increase of the amyloid load. While at the higher doses, A6 treatment increases survival of mice with a decreased amyloid burden. Using a rapid centrifugation assay (RCA), we have shown that low concentrations of A6 promote soluble SDS-resistant oligomers of PrPSc (rSDS-PrPSc), while higher concentrations favour insoluble forms. Brain analysis shows that only mice treated with 10 and 20 mg/kg of A6 exhibit dimeric forms of rSDS-PrPSc. This study shows a dual effect of A6 compound: at low doses, it strenghtens the pathology probably via soluble oligomeric forms favouring the replication of prions. At higher doses, A6 compound would trap part of the infectivity of prions as SDS resistant amorphous aggregates, blocking prion replication, and thus having a “protective” effectA search for structural analogs of A6 compound allowed the identification of a class of commercial antifungals: anilinopyrimidines. This family is composed of 3 molecules: cyprodinil, mepanipyrim and pyrimethanil, used to fight against fungi responsible for the gray mold of fruits. Analysis of many reports have revealed that we are chronically exposed to residues of anilinopyrimidines. In this second study, we evaluated the impact of the 3 fungicides in several models of Alzheimer’s disease (AD) and their consequences on pathological markers. Ex vivo incubation studies associated to kinetics of fibril formation of Aβ1-42 peptides have shown that these compounds interact directly with Aβ peptides and accelerate its kinetics of aggregation. To determine their effects in vivo, we chronically exposed J20 mice to a cocktail of the 3 fungicides through drinking water. Mice were treated with 0.1 μg/L (0.44 nM) of each compound, corresponding to the maximal concentration allowed in the tap water. After 9 months of treatment, analysis of J20 mice showed an increase in the number and surface of plaques in the hippocampus and cortex. To determine the moment when the pro-aggregative effect occurs, a longitudinal study of appearance of aggregates at 3, 6 and 9 months by 2-photon microscopy was done. Our results showed that amyloid plaques increase between 6 and 9 months, and exacerbate vascular amyloid aggregates. Anilinopyrimidines modified the production and clearance of Aβ peptides by increasing BACE1 expression and by decreasing neprilysin expression. Our researches show a role of fungicides in the aggravation of AD
Vinatier, Gérald. "Relation entre l'agrégation et la toxicité dans des modèles de maladies neurodégénératives chez la drosophile." Versailles-St Quentin en Yvelines, 2012. http://www.theses.fr/2012VERS0006.
Повний текст джерелаA common feature of neurodegenerative diseases is the formation of different forms of protein aggregates. During my Ph. D. , I tried to establish the relashionship that links aggregation and toxicity thanks to Drosophila models of Spinocerebellar ataxia type 3 and 7. These models recapitulate the main caracteristics of the corresponding human polyglutamine diseases, making Drosophila a good model to study aggregation and toxicity. My results demonstrate that aggregates in their biochemical definition (high-molecular-mass objects that resist denaturation by boiling SDS) are the major proteic species responsible for the toxicity. One hypothesis could be that aggregates inhibit the proteasomal activity. Thus, I tried to evaluate proteasomal activity in Drosophila expressing a mutant form of Ataxin 3. I have shown that mutated Ataxin 3 is responsible for a decrease in proteasomal activity, which can be blocked by a suppressor of ataxin 3-induced toxicity. However, it seems that proteasomal inhibition is not necessary for the toxicity even if I cannot exclude that this reduction of protein degradation participates to the toxicity of polyglutamine proteins
Gabriel, Pierre. "Equations de transport-fragmentation et applications aux maladies à prions." Paris 6, 2011. http://www.theses.fr/2011PA066144.
Повний текст джерелаSchirer, Alicia. "Les maladies neurodégénératives : étude de peptides modèles, de tissus cérébraux et de liquides céphalorachidiens par (micro)spectroscopie infrarouge et Raman." Thesis, Strasbourg, 2016. http://www.theses.fr/2016STRAF055/document.
Повний текст джерелаNeurodegenerative diseases represent a major societal challenge. So, it is necessary to develop new tools for a better understanding and diagnosing of these diseases. Infrared (IR) and Raman spectroscopies seem to be good candidates since they can characterize the physiopathological conditions of a biological sample. The purpose of this thesis was to apply these methods to the study of model peptides, brain tissues and cerebrospinal fluids (CSF). As a part of brain tissue analysis, IR and Raman spectroscopy were coupled to microscopy in order to combine spectral and spatial information. This methodology improved our understanding of the formation and the role of amyloid plaques in Alzheimer’s disease (AD). Moreover, it allowed to demonstrate the potential of these approaches in future studies on the effect of various treatments against multiple sclerosis. Concerning the study of CSF, IR-ATR and surface enhanced Raman spectroscopy were applied to identify spectroscopic markers of AD and Lewy body disease that could enable early diagnosis of these diseases and discrimination between them
Fernagut, Pierre-Olivier. "Analogues expérimentaux de dégénérescence striatonigrique et développement d'un modèle systémique chez la souris." Bordeaux 2, 2003. http://www.theses.fr/2003BOR21009.
Повний текст джерелаStriatonigral degeneration (SND) is a neurodegenerative disease combining loss of substantia nigra pars compacta (SNc) and striatal neurons. We first validated a stride length test in the mouse and studied the consequences of 3-nitropropionic acid (3-NP) induced lesions and demonstrated a characteristic motor syndrome correlated with the extent of striatal neuronal loss while a dose-dependant motor impairment and neuronal loss in the SNc. We then studied the role of dopamine upon striatal functioning and demonstrated a hypersensitivity to 3-NP in hyperdopaminergic mice, together with spontaneous motor deficits and striatal neuronal loss. Finally, we developped a model of SND using combined MPTP+3-NP intoxication and characterized by a lack of interactions between the two neurotoxins, increased behavioural troubles, motor impairments and striatal injury
Rochet, Marie-Joëlle. "Apports des modèles mathématiques en épidémiologie : points de vue sur la filariose de Bancroft." Lyon 1, 1991. http://www.theses.fr/1991LYO10237.
Повний текст джерелаPons, Salort Margarita. "Modélisation mathématique des interactions multi-hôtes et multi-pathogènes en épidémiologie des maladies infectieuses : conséquences sur la persistance, l'émergence et le contrôle de pathogènes." Paris 6, 2013. http://www.theses.fr/2013PA066640.
Повний текст джерелаCette thèse s'inscrit dans le champ de l'épidémiologie des communautés, une perspective écologique des maladies infectieuses qui prend en compte des communautés de populations hôtes et/ou des communautés microbiennes pour aborder un certain nombre de problèmes actuels en épidémiologie des maladies infectieuses. Des approches mathématiques et statistiques, principalement des modèles de transmission multi-hôtes et multi-pathogènes, sont utilisées pour aborder différentes questions liées à la persistance et à la coexistence de pathogènes. La première partie de cette thèse se concentre sur les mécanismes de persistance de pathogènes multi-hôtes. Nous explorons le rôle de différentes espèces de chauve-souris et de leurs traits biologiques sur la persistance d’un Lyssavirus au sein d’un système de grottes en métapopulation. La deuxième partie s’intéresse aux changements de la diversité de souches d’une espèce dûs aux vaccins qui ciblent un sous-ensemble de ces souches et à l’effet de ces changements sur l’incidence des maladies. Ces questions sont abordées pour les Papillomavirus Humains (HPV) et pour le pneumocoque. Pour HPV, nous explorons d’abord les conditions qui pourraient amener à un remplacement génotypique dû à la vaccination. Nous réexaminons ensuite le potentiel oncogène des types d’HPV agents causals du cancer du col de l’utérus par méta-analyse de données publiées. Pour le pneumocoque, nous étudions comment le vaccin conjugué 7-valent a changé les tendances des méningites à pneumocoque en France et comment une réduction de l’usage d’antibiotiques qui a eu lieu en parallèle à l’introduction du vaccin a modulé le remplacement sérotypique induit par la vaccination
Strul, Daniel. "Correction du volume partiel en tomographie d'émission de positons : applications à l'étude des pathologies neurodégénératives." Paris 11, 2000. http://www.theses.fr/2000PA11T030.
Повний текст джерелаPositron Emission Tomography (PET) allows quantifying in vivo the radioactively labelled molecule in the tissues. Its principal limitation is the partial volume effect (PVE), a systematic Joss of quantification which appears when the phenomena or tissues under study are of small dimensions. PVE is a major problem for the study neurodegenerative diseases, where the partial volume errors increase along with the evolution of the illnesses, due to the progressive atrophy of the brain structures. In this context, our work focussed on the validation and improvement of the GM-PET : methods, the partial volume corrections most commonly used to this date. Those methods are anatomically-guided pixel-by-pixel corrections, where the TEP images are submitted to a post-reconstruction processing using high-resolution anatomical information obtained through computed tomography or magnetic resonance tomography. We have first extensively studied the GM-PET method with regards not only toits nominal performances, but also with regards to its robustness, that is its sensitivity to the various imperfections which can lower the correction quality, namely the pre-processing errors, such as the natomo-functional registration or anatomical image segmentation errors. This validation included several novel works, especially the establishment of a theoretical model for the correction errors and artefacts, and the study of the statistical properties of the GM PET correction when the pre-processing stages are affected by random errors. We have also developed a GM-PET derived methodology for the imaging of small structures, allowing the extension ofthis method to the study of the neurodegenerative disease animal models. To achieve this, we have initially developed and validated a TEP-image resampling algorithm based on cubic spline interpolation. This resampling has consequently been integrated in the PVE correction method, thus allowing an optimal anatomical data exploitation. Last, the modified correction algorithm, after being validated by comparison with the standard GM-PET method, was tested in realistic conditions through its application to a monkey model of the Huntington's disease
Andraud, Mathieu. "Modélisation de la dynamique d’infection par le circovirus porcin de type 2 (PCV-2) dans un élevage de type naisseur-engraisseur." Rennes 1, 2008. http://www.theses.fr/2008REN1S143.
Повний текст джерелаA stochastic individual-based model has been developed to represent the population dynamics within a pig production herd and coupled with a PCV-2 specific epidemiological model. Two experimental transmission studies were carried out to estimate accurately the main parameters of the epidemiological model. The resulting model has been used to evaluate the influence of husbandry and control measures on PCV-2 within herd infection dynamics, previously identified as a major risk factor for post-weaning multisystemic wasting syndrome
Biane, Célia. "Reprogrammation comportementale : modèles, algorithmes et application aux maladies complexes." Thesis, Université Paris-Saclay (ComUE), 2018. http://www.theses.fr/2018SACLE050.
Повний текст джерелаComplex diseases such as cancer and Alzheimer's are caused by multiple molecular perturbations responsible for pathological cellular behavior. A major challenge of precision medicine is the identification of the molecular perturbations induced by the disease and the therapies from their consequences on cell phenotypes. We define a model of complex diseases, called behavioral reprogramming, that assimilates the molecular perturbations to alterations of the dynamic local functions of discrete dynamical systems inducing a reprogramming of the global dynamics of the network. This modeling framework relies on the one hand, on Control Boolean networks, which are Boolean networks containing control parameters modeling the perturbations and, on the other hand, the definition of reprogramming modes (Possibility, Necessity) expressing the objective of the behavioral reprogramming. From this framework, we demonstrate that the computation of the cores, namely, the minimal sets of action allowing reprogramming is a problem of abductive inference in propositional logic. Using historical methods computing the prime implicants of Boolean functions, we develop two methods computing all the reprogramming cores.Finally, we evaluate the modeling framework for the identification of perturbations responsible for the transformation of a healthy cell into a cancercell and the discovery of therapeutic targets ona model of breast cancer. In particular, we showthat the perturbations inferred by our methods a recompatible with biological knowledge by discriminating oncogenes and tumor suppressor genes and by recovering the causal of the BRCA1 gene. In addition, the method recovers the synthetic lethality phenomenon between PARP1 and BRCA1 that constitutes an optimal anti-cancer treatment because it specifically targets tumor cells
Sarrot-Reynauld, Françoise. "Influence de la comorbidité sur le pronostic des accidents vasculaires cérébraux : de l'intuition à la modélisation." Université Joseph Fourier (Grenoble), 1999. http://www.theses.fr/1999GRE19011.
Повний текст джерелаCeyzériat, Kelly. "Modulation de la réactivité astrocytaire par ciblage de la voie JAK2-STAT3 : conséquences dans des modèles murins de la maladie d’Alzheimer." Thesis, Université Paris-Saclay (ComUE), 2017. http://www.theses.fr/2017SACLS556/document.
Повний текст джерелаAstrocytes are emerging as key players in brain physiology. In Alzheimer’s disease (AD), astrocytes become reactive. Astrocyte reactivity (AR) is essentially characterized by morphological changes. But how the normal supportive functions of astrocytes are changed by their reactive state is unclear. Moreover, signaling cascades leading to AR are not yet determined. In this study, we aim to: 1/ demonstrate the JAK2-STAT3 pathway (Janus Kinase 2 - Signal Transducer and Activator of Transcription 3) is responsible for AR in neurodegenerative diseases ; 2/ understand the contribution of reactive astrocytes to molecular, cellular and functional alterations in AD. We already reported that the JAK2- STAT3 pathway is a central cascade for AR (Ben Haim et al., 2015). Here, we demonstrate, with new molecular tools based on viral vectors, that this pathway is necessary and sufficient to AR. Our results also show that the modulation of AR in two AD mouse models (APP/PS1dE9 and 3xTg-AD mice) influence several pathological hallmarks, but in a context-dependent manner. Overall, this work has generated new original tools to study reactive astrocytes in situ and it underlines the importance and complexity of their functions in neurodegenerative diseases
Silhol, Romain. "Estimation et validation de modèles individus-centrés de propagation épidémique : la varicelle en Corse." Paris 6, 2011. http://www.theses.fr/2011PA066180.
Повний текст джерелаVan, de Velde Nicolas. "Modélisation de l'efficacité populationnelle du vaccin contre le virus du papillome humain au Canada." Thesis, Université Laval, 2013. http://www.theses.ulaval.ca/2013/29766/29766.pdf.
Повний текст джерелаObjective: The two main objectives of this thesis were to develop 1) mathematical models to predict the population-level impact of HPV vaccination in Canada, and 2) methods to quantify uncertainty around model predictions. Methods: We developed three mathematical models: 1) a static compartmental model of cervical cancer natural history (Model 1), 2) an individual-based dynamic model of HPV infection (Model 2), and 3) the first individual-based transmission-dynamic model of partnership formation and dissolution, and natural history of multi-type HPV infection and disease (anogenital warts, and cervical, anogenital and oropharyngeal cancers) (Model 3). For each model, an extensive fitting procedure was conducted, which identified multiple posterior parameter combinations (out of hundreds of thousands of prior parameter sets) that fit simultaneously highly stratified behavioral and epidemiologic data, taken from the literature, population-based datasets, and original studies. Parameter uncertainty was illustrated by presenting the median [10th;90th percentiles] of predictions, using the posterior parameter combinations. Sensitivity analysis was conducted varying vaccine efficacy, duration of protection, coverage and vaccination strategies. Results: We provided the following evidence for HPV vaccination recommendations. Models 1-3 predicted that girls-only HPV vaccination can substantially reduce HPV-related burden of disease. Predictions were most sensitive to duration of vaccine protection. Model 3 predicted that the bivalent vaccine will be slightly more effective at preventing cervical cancer in the longer term. However, the quadrivalent vaccine will substantially reduce anogenital warts. Finally, the candidate nonavalent vaccine has the potential to produce substantial incremental benefits if its efficacy and duration of protection are at least 85% and 30 years, respectively. From a methodological point of view, we illustrated that parameter uncertainty surrounding HPV natural history parameters is important and must be presented when providing predictions to decision makers. Finally, we identified key structural assumptions that influence predictions: herd immunity, natural immunity, partnership duration, individual genotypes and vaccine waning function. Conclusion: We developed increasingly sophisticated HPV models and calibration techniques to keep track with the increasingly complex policy questions being asked. Our final model is being used to examine the impact of HPV vaccination on health inequalities, evaluate the cost-effectiveness of HPV vaccination, and optimize screening.
Leclerc, Melen. "Approche par modélisation et expérimentation du développement spatio-temporel des maladies telluriques : le cas du pathosystème betterave à sucre – Rhizoctonia solani." Rennes, Agrocampus Ouest, 2013. http://www.theses.fr/2013NSARC109.
Повний текст джерелаNowadays it is still difficult to predict and control the spread of soilborne diseases that cause substantial damage in crop systems. The aim of this epidemiological interdisciplinary work is to propose models for the spatio-temporal spread of soilborne pathogens in order to point out key parameters for the control of soilborne diseases. This thesis considers the spread of Rhizoctonia solani on sugar beet as an example pathosystem and focuses on three main problems. First, we use experimental measures of the dispersal of the pathogen to parameterise a stochastic spatially explicit model and we show that host growth can trigger the development of epidemics by causing a switch from non-invasive to invasive behaviour. Second, using experimental data we build an age-varying model for the distribution of the incubation period that links hidden infections and above-ground observations of the disease. Then, we investigate the cryptic behaviour of epidemics by using a hierarchical model that considers a realistic incubation period. Third, we use a spatially-implicit model to estimate rates of infection from temporal disease data, and, to analyse the effects of biofumigation on epidemics. These parameters are integrated into an individual-based model to predict the stochastic development of epidemics. Our results confirm that biofumigation only permits a partial control and suggest that this biological control reduces uncertainty of the cryptic development of the disease. To finish with, we discuss the results of the thesis and we present the perspectives of this work
Soubeyrand, Samuel. "Spécifier un processus caché non modélisé en déterminant le lien asymptotique entre résidus et processus caché : application à l'analyse de la variabilité dans les expériences de propagation des rouilles du blé." Montpellier 2, 2005. http://www.theses.fr/2005MON20075.
Повний текст джерелаBrochier, Camille. "Analyse des transcriptomes du cerveau de souris : mise en évidence de patrons régionaux d'expression conservés chez l'homme et altérés dans des modèles de maladies neurodégénératives." Phd thesis, Université Paris Sud - Paris XI, 2007. http://tel.archives-ouvertes.fr/tel-00361207.
Повний текст джерелаBrochier, Camille. "Analyse des transcriptomes du cerveau de souris : Mise en évidence de patrons régionaux d’expression conservés chez l’homme et altérés dans des modèles de maladies neurodégénératives." Paris 11, 2007. http://www.theses.fr/2007PA112123.
Повний текст джерелаIn order to get a better understanding of brain complexity at a molecular level, we explored the mouse brain transcriptome using the Serial Analysis of Gene Expression method. SAGE libraries were generated from 11 mouse brain territories, including six cortical regions, striatum, accumbens nucleus, thalamus, substantia nigra and ventral tegmental area. The entire project delivered 1. 2 million SAGE tags, allowing the detection of rare mRNAs. Comparison of all transcriptomes revealed 308 transcripts differentially expressed, a number of which have no documented function. We further analyzed the expression profiles by real-time RT-PCR or in situ hybridization (ISH). Since the brain is a heterogeneous organ, it was important to determine the cell types that are expressing the novel markers. A combination of in situ hybridization with immunohistochemistry showed the expression of 3 midbrain-enriched mRNAs in dopaminergic neurons. We tested whether mouse markers could be human markers. There was a good overall conservation of expression patterns in both species. To evaluate the assumption that genes predominantly expressed in a given brain structure may indeed be relevant to its function, we chose pathophysiological conditions that target specific neuron populations. Using quantitative RT-PCR, we so far measured the abundance of striatum- or cortex-enriched transcripts in the mouse R6/2 genetic model of Huntington’s disease. Likewise, we showed the regulation of transcripts enriched in the striatum or substantia nigra in pharmacological rodent models of Parkinson’s disease, in which the nigro-striatal dopaminergic pathway has been lesioned
Hilber, Pascal. "Conséquences d'une neurodégénérescence précoce du cortex cérébelleux sur le vieillissement chez la souris : utilisation d'un mutant neurologique, la souris Lurcher." Rouen, 1999. http://www.theses.fr/1999ROUES004.
Повний текст джерелаDe, Conto Véronique. "Importance du microenvironnement dans les modèles cérébraux in vitro pour le criblage phénotypique." Thesis, Université de Lille (2018-2021), 2021. http://www.theses.fr/2021LILUS046.
Повний текст джерелаAbout 90% of drug candidates fail in clinical trials, for efficacy- and toxicity-related reasons, which often involve the Central Nervous System (CNS). This high failure rate highlights a lack of relevance in experimental models used upstream, including human in vitro models. Indeed, they do not take into account the complexity of the CNS, in which neurons are organized in 3 dimensions (3D) and interact with their microenvironment, composed of cells, soluble factors and extracellular matrix (ECM). The objectives of this PhD were i) to study the influence of these three microenvironment components on neuronal cells in cerebral in vitro models by automatized cellular imaging, and ii) to develop more relevant cerebral in vitro models for phenotypic screening, to assess neurotoxic or therapeutic effects, in the frame of Parkinson’s Disease (PD).First, the BIOMIMESYS® Brain technology has been developed. This acid hyaluronic based-matrix allows the simulation of the ECM and a 3D culture of cerebral cells in 96-well plates. The sensitivity of Luhmes cells, a dopaminergic neuronal cell line, to PD inducers has been studied: the cells displayed a lower sensitivity in BIOMIMESYS® Brain compared to cells cultured in 2 dimensions (2D). This difference was explained by two phenomena: a partial retention of toxic molecules in the matrix, and a lower neuronal maturity compared to cells cultured in 2D.The importance of the cellular microenvironment has been studied through a co-culture of Luhmes cells and primary human astrocytes in 2D. This co-culture has then been transposed in BIOMIMESYS® matrix, to form a complex model including both the glial and the matricial microenvironments.In parallel, the influence of the molecular microenvironment has been studied on the SH-SY5Y cells, a cell line derived from a neuroblastoma, commonly used for neurotoxicity assessment. In this study, the 24 major differentiation media described in the literature to differentiate these cells into neurons have been screened. The 3 most differentiating conditions in terms of proliferation slowdown and neurite elongation have been selected: retinoic acid, staurosporine, and cyclic Adenosine Monophosphate (cAMP) combined to B21 supplement. The neuronal protein marker expression and the cell sensitivity to compounds of known-toxicity have been measured, in 2D and in 3D in BIOMIMESYS® Brain. Both maturity and sensitivity of these neurons varied according to the differentiation medium, and were higher in B21+cAMP. The 3D cell culture modified also the cell response, with a lower sensitivity of cells cultured in 2D.This PhD highlighted that the microenvironment of neurons, including the ECM, the glial cells and the soluble factors, can modify the neuronal response in vitro, and should thus be considered carefully in academic research and as early as possible in the drug discovery industrial process
Allorent, Delphine. "Analyse et modélisation épidémiologique de la tache angulaire du haricot ("Phaseolus vulgaris") due à "Phaeoisariopsis griseola"." Montpellier 2, 2005. http://www.theses.fr/2005MON20041.
Повний текст джерелаDemin, Ivan. "Modélisations mathématiques de l’hématopoïèse et des maladies sanguines." Thesis, Lyon 1, 2009. http://www.theses.fr/2009LYO10333/document.
Повний текст джерелаThis PhD thesis is devoted to mathematical modelling of haematopoiesis and blood diseases. We investigate several models, which deal with different and complementary aspects of haematopoiesis.The first part of the thesis concerns a multi-scale model of erythropoiesis where intracellular regulatory networks, which determine cell choice between self-renewal, differentiation and apoptosis, are coupled with dynamics of cell populations. Using experimental data on anemia in mice, we evaluate the roles of different feedback mechanisms in response to stress situations. At the next stage of modelling, spatial cell distribution in the bone marrow is taken into account, the question which has not been studied before. We describe normal haematopoiesis with a system of reaction-diffusion-convection equations and prove existence of a stationary cell distribution. We then introduce malignant cells into the model. For some parameter values the disease free solution becomes unstable and another one, which corresponds to leukaemia, appears. This leads to the formation of tumour which spreads in the bone marrow as a travelling wave. The speed of its propagation is studied analytically and numerically. Bone marrow cells exchange different signals that regulate cell behaviour. We study, next, an integro-differential equation which describes cell communication and prove the existence of travelling wave solutions using topological degree and the Leray-Schauder method. Individual based approach is used to study distribution of different cell types in the bone marrow. Finally, we investigate a Physiologically Based Pharmacokinetics-Pharmacodynamics model of leukaemia treatment with AraC drug. AraC acts as chemotherapy, inducing apoptosis of all proliferating cells, normal and malignant. Pharmacokinetics provides the evolution of intracellular AraC. This, in turn, determines cell population dynamics and, consequently, efficacy of treatment with different protocols
Koval, Igor. "Learning Multimodal Digital Models of Disease Progression from Longitudinal Data : Methods & Algorithms for the Description, Prediction and Simulation of Alzheimer’s Disease Progression." Thesis, Institut polytechnique de Paris, 2020. http://www.theses.fr/2020IPPAX008.
Повний текст джерелаThis thesis focuses on the statistical learning of digital models of neurodegenerative disease progression, especially Alzheimer's disease. It aims at reconstructing the complex and heterogeneous dynamic of evolution of the structure, the functions and the cognitive abilities of the brain, at both an average and individual level. To do so, we consider a mixed-effects model that, based on longitudinal data, namely repeated observations per subjects that present multiple modalities, in parallel recombines the individual spatiotemporal trajectories into a group-average scenario of change, and, estimates the variability of this characteristic progression which characterizes the individual trajectories. This variability results from a temporal un-alignment (in term of pace of progression and age at disease onset) along with a spatial variability that takes the form of a modification in the sequence of events that appear during the course of the disease. The different parts of the thesis are ordered in a coherent sequence: from the medical problematic, followed by the statistical model introduced to tackle the aforementioned challenge and its application to the description of the course of Alzheimer's disease, and, finally, numerical tools developed to make the previous model available to the medical community
Diguet, Elsa. "Dégénérescence striatonigrique induite chez la souris par le MPTP et l'acide 3-nitropropionique : interactions dopamine/glutamate et perspectives thérapeutiques." Bordeaux 2, 2005. http://www.theses.fr/2005BOR21213.
Повний текст джерелаStriatonigral degeneration (SND), the core pathology underlying levodopaunresponsive parkinsonism associated with multiple system atrophy (MSA), incorporates loss of nigral dopaminergic and striatal GABAergic neurons. The aims of the study were to explore the long term behavioral and histopathological consequences of combined MPTP + 3 - nitropropionic acid (3-NP) intoxication in C57B1/6 mice and its ability to reproduce the neuropathological hallmarks of SND. As dopamine is involved in the modulation of striatal excitotoxic processes, we also studied 1) - the effect of constitutive hyperdopaminergia both on the 3-NP vulnerability and on the behavioral motor performances in the dopamine transporter knock-out mice and 2) - the consequences of levodopa treatment in the phenotypic SND mouse model. Lastly, the potential interest of the antiglutamatergic and anti-inflammatory strategies were assessed on striatal or striatonigral neurodegeneration. These results have some clinical significance for the management of the parkinson variant of MSA
Tournoud, Maud. "Adaptation du modèle de temps de promotion à l'étude du délai de détection du VIH chez l'enfant et de la survenue d'autres maladies infectieuses." Lyon 1, 2006. http://www.theses.fr/2006LYO10166.
Повний текст джерелаTo study the delay between transmission and detection of an infectious disease, particularly in situation of multiple exposures, we have developed a survival model, adapted to interval censored data. Initially developed in cancerology, this model enables to take into account a proportion of patients who will not undergo the studied event, ie. Patients who were not contaminated. In a first example that deals with mother-to-child transmission of HIV-1 in South Africa, we have studied the influence of infant feeding practices (formula, exclusive breastfeeding or mixed feeding) on the probability of HIV-1 transmission at birth and during breastfeeding. It was shown that the probability of transmission at birth was not significantly modified by early breastfeeding practice. While breastfeeding continued to be exclusive there was a negligible risk of transmission in comparison with that observed with mixed feeding. In a second example on nosocomial urinary tract infections in intensive care units, it was shown that the proportion of infections attributable to the catheter placement was ten fold smaller than the proportion of infections attributable to its long-term use
Vergeur-Laborie, Valérie. "Simulation numérique de l'écoulement artériel cérébral : contribution à l'étude des conséquences hémodynamiques des sténoses situées en amont et en aval du polygone de Willis." Toulouse 3, 1993. http://www.theses.fr/1993TOU30168.
Повний текст джерелаD'Orange, Marie. "Utilisation de nouveaux modèles rongeurs de tauopathie pure, obtenus par transfert de gène, pour caractériser le lien entre l’agrégation de Tau et sa toxicité." Thesis, Université Paris-Saclay (ComUE), 2016. http://www.theses.fr/2016SACLS339/document.
Повний текст джерелаTauopathies are neurodegenerative diseases characterized by the aggregation of Tau protein. Despite this common hallmark, tauopathies exhibit a wide variety of clinical and anatomo-pathological presentations, which may possibly result from different pathological mechanisms. One hypothesized common mechanism, however, implicates small oligomeric aggregates as drivers of Tau-induced toxicity.The aim of this project was to develop models of sporadic and genetic tauopathies, using adeno-associated viruses to mediate gene transfer of human Tau to the rat brain. Three different constructs were used, each giving rise to a specific phenotype. First, hTAUWT overexpression led to a strong hyperphosphorylation of the protein which was associated with neurotoxicity in absence of any significant aggregation. Its co-expression with the pro-aggregation peptide TauRD-ΔK280 in the hTAUProAggr group strongly promoted its aggregation, with neuroprotective effects. hTAUP301L construct led to aggregation into soluble species as well as mature aggregates accompanied with an intermediate toxicity. Those results support the hypothesis that soluble oligomeric species are key players of Tau-induced neurodegeneration.Those fast developing models, obtained through similar overexpression of human Tau, thus recapitulated the phenotypic variability observed in human tauopathies. Those should prove useful in the future to study mechanisms underlying the toxicity of various Tau species. Those could also serve to study the specificity and selectivity of Tau-directed tracers for positon emission tomography (PET) imaging
Deguil, Julie. "Perturbations du contrôle traductionnel et troubles cognitifs dans un modèle expérimental de la maladie de Parkinson : études de neuroprotection." Poitiers, 2009. http://www.theses.fr/2009POIT1801.
Повний текст джерелаFouchet, David. "Rôle des anticorps maternels dans le changement d' impact d'une maladie infectieuse : impact du choix du modèle sur la compréhension des relations hôte parasites." Lyon 1, 2006. http://www.theses.fr/2006LYO10151.
Повний текст джерелаBelarbi, Karim Ali. "Caractérisation d'un modèle murin de dégénérescence neurofibrillaire : étude de conséquences fonctionnelles de la pathologie tau potentiellement impliquées dans les phases précoces de la maladie d'Alzheimer." Lille 2, 2009. http://www.theses.fr/2009LIL2S018.
Повний текст джерелаKhalil, Bilal. "Importance du contrôle qualité des mitochondries dans les maladies neurodégénératives : analyse cellulaire et génétique dans des modèles drosophile de la maladie de Huntington et de la sclérose latérale amyotrophique." Thesis, Aix-Marseille, 2016. http://www.theses.fr/2016AIXM5054.
Повний текст джерелаMitochondria are the main energy source in neurons. Mitochondrial defects contribute to the development of neurodegenerative diseases, however they can be countered by a quality control system. The purpose of my thesis has been to determine if this system is dysregulated in Huntington’s disease (HD) and in amyotrophic lateral sclerosis (ALS) and if restoring it can be neuroprotective, by mainly using Drosophila models. HD, which is characterized by loss of striatal neurons, is caused by the mutant Huntingtin protein (mHtt). We showed that mHtt induces the accumulation of mitochondria in the retina. This could be due to a defect in mitophagy, a mechanism which allows the elimination of defective mitochondria and which is orchestrated by the protein PINK1. Interestingly, PINK1 overexpression ameliorates the abnormal phenotype of flies expressing mHtt. I also got interested in ALS, in which motor neurons degenerate, and mainly in the TDP-43 gene which is a major contributor to the disease. We showed that TDP-43 overexpression in Drosophila neurons leads to fragmentation of mitochondria due to decreased expression levels of the mitofusin gene. The latter controls the fusion process between healthy and damaged mitochondria and therefore the organelle integrity. We show that Mitofusin overexpression ameliorates locomotor defects and abnormal neuronal activity in flies expressing TDP-43. Our results show the importance of mitochondrial quality control in the pathogenesis of these diseases, and that reinforcing it can be beneficial
Duret, Marie-Pierre. "Les modèles en phytopathologie : étude du champignon Sclerotinia sclerotiorum sur colza (Brassica napus)." Lyon 1, 1992. http://www.theses.fr/1992LYO10120.
Повний текст джерелаAllard, Antoine. "Modélisation mathématique en épidémiologie par réseaux de contacts : introduction de l'hétérogénéité dans la transmissibilité." Thesis, Université Laval, 2008. http://www.theses.ulaval.ca/2008/25738/25738.pdf.
Повний текст джерелаCiss, Mamadou. "Modélisation spatio-temporelle de la multiplication-dispersion du puceron des épis du blé à l'échelle de la France." Rennes, Agrocampus Ouest, 2013. http://www.theses.fr/2013NSARG012.
Повний текст джерелаThe grain aphid Sitobion avenae is a major agricultural pest in Western Europe. It causes occasionnaly strong demages during spring, decreasing yield up to several tons by hectare in case of large build up. The overgrowths are difficult to forecast and many insecticide sprays are unjustified. Therefore it is important to design a spatially explicit Decision Support System (DSS) in order to optimize insecticide treatments use. In a first step, we deterministically developed a mathematical model based on convection-diffusion-reaction equations, representing aphid population dynamics from the beginning of the spring to mid-summer. Secondly the parameters of the model (growth rate, landing rate, take-off rate, diffusion coefficient and initial conditions) were estimated from field data between- 1975 to 2011, or taken from the literature. Finally, numerical simulations at France scale described a both spatial and temporal irregular wave by considering agro-climatic factors in the landscape (winter and spring temperatures, winter wheat surfaces and wheat phenology) and their variations at a 25 km2 scale
Farah, Ahcène. "Contribution à la modélisation mathématique de la biomécanique de la pompe cardiaque : application à l'analyse des déformations pathologiques du ventricule gauche." Vandoeuvre-les-Nancy, INPL, 1989. http://www.theses.fr/1989NAN10405.
Повний текст джерелаCourcoul-Lochet, Aurélie. "Modélisation de la propagation de Coxiella burnetii en troupeau bovin laitier." Rennes 1, 2010. https://tel.archives-ouvertes.fr/tel-00591053.
Повний текст джерелаLa fièvre Q est une zoonose mondialement répandue due à Coxiella burnetii. Elle peut engendrer des troubles de la reproduction chez les ruminants. De plus, ces derniers constituent la principale source d’infection pour l’Homme. Il est donc nécessaire de lutter contre la propagation de C. Burnetii en troupeaux bovins pour améliorer les performances de ces élevages et limiter le risque zoonotique. L’objectif de cette thèse a été de mieux comprendre la propagation de l’infection au sein d’un troupeau bovin laitier, afin de mieux la contrôler. Un modèle épidémiologique stochastique, individu-centré et en temps discret représentant la propagation intra-troupeau de C. Burnetii a été développé. Ses paramètres ont été estimés à partir de données de terrain en utilisant une approche Bayésienne. Une forte hétérogénéité entre vaches excrétrices ayant été rapportée, les voies et niveaux d’excrétion ont été explicitement représentés dans une variante du premier modèle. Les paramètres influençant le plus la dynamique d’infection, identifiés par une analyse de sensibilité, étaient les niveaux d’excrétion, les caractéristiques de la bactérie dans l’environnement et certains traits physiologiques des animaux. Enfin, trois stratégies de vaccination ont été représentées dans le modèle et leurs efficacités à long terme ont été comparées par simulation. La vaccination des vaches et génisses pendant 10 ans s’est avérée la stratégie la plus efficace. En conclusion, outre une meilleure compréhension de la dynamique d’infection, ce travail fournit une aide à la priorisation des besoins de recherche et à la définition des mesures efficaces pour contrôler la fièvre Q en troupeaux bovins laitiers
Foucault, Laura. "Evaluation des effets potentiels anti-inflammatoires et neuroprotecteurs d'un agoniste des récepteurs nicotiniques de l'acétylcholine alpha 7 dans un modèle in vivo de neuroinflammation chez le rat." Thesis, Tours, 2018. http://www.theses.fr/2018TOUR3314.
Повний текст джерелаNeuroinflammation is a key component of the pathophysiology of neurodegenerative diseases. To date, the management of patients with neurodegenerative diseases is based on symptomatic treatments. In recent years, the scientific community has focused its research on the regulation of the neuroinflammation. In this thesis, we observed the potential anti-inflammatory and neuroprotective effects induced by an alpha 7 nicotinic acetylcholine receptor agonist (α7 nAChR), PHA 543613, in an in vivo neuroinflammatory model. These observations led us to continue our investigations through a mechanistic approach, and more precisely, to quantify the expression of a phase II antioxidant enzyme. By analogy with the peripheral anti-inflammatory cholinergic pathway, the activation of α7 nAChR localised on glial cells leads to the overexpression of heme oxygenase 1
Eymard, Nathalie. "Modélisation hybride de l’hématopoïèse et de maladies sanguines." Thesis, Lyon 1, 2014. http://www.theses.fr/2014LYO10340/document.
Повний текст джерелаThe thesis is devoted to mathematical modeling of hematopoiesis and blood diseases. It is based on the development of hybrid discrete continuous models and to their applications to investigate production of blood cell (hematopoiesis) and blood diseases such as lymphoma and myeloma. The first part of the thesis concerns production of blood cells in the bone marrow. We will mainly study production of red blood cells, erythropoiesis. In mammals erythropoiesis occurs in special structures, erythroblastic islands. Their functioning is determined by complex intracellular and extracellular regulations which include various cell types, hormones and growth factors. The results of modeling are compared with biological and medical data for humans and mice. The purpose of the second part of the thesis is to model some blood diseases, T cell Lymphoblastic lymphoma (T-LBL) and multiple myeloma (MM) and their treatment. TLBL develops in the thymus and it affects the immune system. In MM malignant cells invade the bone marrow and destroy erythroblastic islands preventing normal functioning of erythropoiesis. We developed multi-scale models of these diseases in order to take into account intracellular molecular regulation, cellular level and extracellular regulation. The response to treatment depends on the individual characteristics of the patients. Various scenarios are considered including successful treatment, relapse and development of the resistance to treatment. The last part of the thesis is devoted to a reaction-diffusion model which can be used to describe Darwinian evolution of cancer cells. Existence of pulse solutions, which can describe localized cell populations and their evolution, is proved
Guigal, Pierre-Michel. "Modélisation de la propagation infectieuse dans un réseau organise d'individus : apport de la prétopologie et de la géometrie fractale." Lyon, INSA, 1995. http://www.theses.fr/1995ISAL0064.
Повний текст джерелаThis report deals with forecast and diagnosis modelling of a disease wich spread is intimately linked to the population organisation. According to some hypothesis, we bring to the fore that the characteristics of susceptibility (defined as local relations) give raise to a kind of global organisation in the population. This characteristic forms a main factor in forecasting. Scrapie in sheep give us a concrete support for this approach. The pretopological theory allows us to design a simplified model of the population organisation and suggests that a scale law may structure a network of local relations. This property leads to look for a self similar process in the clusters consitution. We implement pattern recognition methods based on syntax to design a model of cluster constitution on a network of local relations. This on reveals the self similarity property wich allows us to formulate the aim of analysis in the frame of fractal geometry. An adaptation of the Zifp-Mandelbrot law to hierarchic organisation of the local relations enable us to propose a parametric method of anlaysis. We use these results in a new kind of compartmental model that give an analytic representation of the complex phenomena of spreak in a network. In order to validate this synthetic approach of complex spreak in a network, we propose a cellular automaton for simulation of local events as relation and spread. We obtain similar results by the two ways. This result suggests that the synthetic approach is operative
Kretowski, Marek. "Modélisation et classification en imagerie médical." Rennes 1, 2002. http://www.theses.fr/2002REN10089.
Повний текст джерела