Dissertationen zum Thema „Simulation – Dissertation universitaire“
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Vuillod, Bruno. „Stratégie de modélisation multi-fidélité via une approche système incluant des métamodèles basés sur les entités NURBS“. Electronic Thesis or Diss., Paris, HESAM, 2024. http://www.theses.fr/2024HESAE003.
Der volle Inhalt der QuelleThe more complex the problem, the greater the amount of computational resources needed to simulate it. On the other hand, the need for accuracy in the results of a system will not be the same depending on its design phase and the domain studied. The goal of this thesis is to propose a fast, low-cost multi-fidelity modeling strategy. To meet this need, a hybrid modeling approach is developed that combines Model-Based System Engineering (MBSE) and a metamodel based on Non-Uniform Rational Basis-Spline (NURBS) hypersurfaces. More specifically, the scientific challenge of this work is to develop a metamodel based on NURBS entities to simulate the behavior of highly nonlinear systems that require high fidelity modeling but are capable of providing results in real time to be compatible with the MBSE approach. In this context, the NURBS entity-based metamodel is obtained as a solution to an optimization problem solved with a gradient algorithm. In addition, a smoothing term is included in the problem formulation, not only to reduce the influence of any spurious nonlinearities in the training database, but also to limit the phenomenon of overfitting. The technical and scientific challenge of this work is to couple the general MBSE approach with the NURBS-based metamodel
Robberecht, Lieven. „Développement d’un simulateur canalaire endodontique pour des applications pédagogiques et de recherche“. Thesis, Lille 2, 2015. http://www.theses.fr/2015LIL2S073.
Der volle Inhalt der QuelleEndodontic therapy is often complicated and technically demanding. The “in vitro model” to simulate natural human teeth is highly needed for teaching and training dental students in pre-clinics or dental surgeons in continuing dental education courses. Moreover, remarkable development and research of endodontic technology also requires good model for in vitro performance evaluation prior to use on patients. Different practice models, including extracted human teeth, animal teeth or simulated root canals in epoxy resin blocks, etc., cannot satisfy the specific requirements. The objective of this thesis is to develop a process of fabricating a biomimetic dental root canal model (RCM) with a composition, microstructure and anatomy close to a natural tooth root. In order to overcome the limitations of existing RCMs, a ceramic root canal model (C-RCM) was developed, based on microporous hydroxyapatite (HAp), shaped by the casting method, with internal pulp cavity moulded by stereolithographic technique and finished by resin impregnation (to improve the tactile sensation during endodontic instrumentation). Many properties of this SC were shown comparable to the natural dental root: the same mineral component (HAp), porosity of 0-30%, the pore size of 0.8-5 µm, the good hardness (65-500 HV), the potential of customization of variable canal morphology, the suitable radio-opacity, etc. The pilot study on the evaluation of the application of this C-RCM by dental students was carried out and confirmed that better radiological behaviour for C-RCM than commercial resin RCM. This canal simulator poses no risk of infection, available in large numbers, allowing the objective assessment through its uniformity, therefore, well suits the endodontic practices and presents promising potential for training student or research on new endodontic technology
Fındık, Volkan. „Simulations atomistiques de la réaction d’acétylation d’amines et de l’inhibition covalente de l’enzyme Phosphoinositide 3-kinase (PI3K)“. Electronic Thesis or Diss., Université de Lorraine, 2022. http://www.theses.fr/2022LORR0266.
Der volle Inhalt der QuelleTargeted Covalent Inhibitors (TCIs) hold great promise for search of new drugs. They offer a number of potential advantages over traditional reversible inhibitors, such as extended residence time, increased potency, and the ability to make modifications for effective design. Kinase inhibitors are the most common examples of TCIs. Phosphoinositide 3-kinase (PI3K) enzymes are important drug targets in oncology as they are involved in the signaling pathway for many cellular functions such as growth control, metabolism and translation initiation. Lysine (Lys) residues have gained increasing interest as an alternative for targeted covalent inhibition. Recently, the first selective and irreversible inhibitors with ester groups as electrophilic head targeting the Lys779 residue and covalently inactivating the PI3Kδ enzyme were reported. The main objective of this thesis is to elucidate the mechanism of the covalent inhibition of PI3Kδ by these ester inhibitors in order to assist future design of new inhibitors with superior activities. Prior to the mechanistic studies on the enzyme, initially, we performed ab initio and DFT calculations on the model reaction between methylamine and methyl, phenyl and p-NO2 phenyl acetates in aqueous solution. The same model systems were then studied by the "dual-level" QM/MM molecular dynamics approach. For the “low-level” option, PM3/TIP3P umbrella sampling QM/MM simulations were applied for the sampling. The obtained structures were then used to obtain perturbative corrections to the free energy with a “high-level” QM region at the M06-2X/6-311+G(d,p) level. The results show that thefirst step involves the formation of the zwitterionic tetrahedral intermediate. Then, for sufficiently electrophilic esters, such as the p-NO2 derivative, the reaction proceeds by dissociation of the zwitterion as an ion pair, followed by proton transfer leading to the formation of the expected products. We, then, employed similar computational tools to shed light on the mechanistic aspects of the enzyme. First, an active site model of the enzyme was built through classical molecular dynamics simulations. Then, ONIOM QM:QM approach at the M06-2X/6 -31+G(d,p):PM6 level was applied to get possible reaction mechanisms in this active site. These calculations guided us to refine the reaction mechanisms in enzyme environment which globally confirm the steps obtained from the small model system. We finally used this information to approach a dynamic QM/MM study on the enzyme using the same“dual-level” protocol established for the small model system, which allowed us to obtain the free energy profile of the inhibition mechanism of PI3Kδ for p-NO2 derivative of the ester inhibitor. The calculated barrier is in good agreement with the available experimental kinetic data, which validates the proposed theoretical approach and the obtained mechanisms. Through the elucidation of the inhibition mechanism of previously experimentally tested compounds, our study paves the way for the discovery of new inhibitors with improved activity with the help of theoretical chemistry tools
Ejjaaouani, Ksander. „Conception du modèle de programmation INKS pour la séparation des préoccupations algorithmiques et d’optimisation dans les codes de simulation numérique : application à la résolution du système Vlasov/Poisson 6D“. Thesis, Strasbourg, 2019. http://www.theses.fr/2019STRAD037.
Der volle Inhalt der QuelleThe InKS programming model aims to improve readability portability and maintainability of simulation codes as well as boosting developer productivity. To fulfill these objectives, InKS proposes two languages, each dedicated to a specific concern. First, InKS PIA provides concepts to express simulation algorithms with no concerns for optimization. Once this foundation is set, InKSPSO enables optimization specialists to reuse the algorithm in order to specify the optimization part. The model offers to write numerous versions of the optimizations, typically one per architecture, from a single algorithm. This strategy limits the rewriting of code for each new optimization specification, boosting developer productivity.We have evaluated the InKS programming model by using it to implement the 6D Vlasov-Poisson solver and compared our version with a Fortran one. This evaluation highlighted that, in addition to the separation of concerns, the InKS approach is not more complex that traditional ones while offering the same performance. Moreover, using the algorithm, it is able to generate valid code for non-critical parts of code, leaving optimization specialists more time to focus on optimizing the computation intensive parts
Hullo, Marie. „Place des nanoparticules pour lutter contre la radio-résistance du cancer du sein : impact de l’hétérogénéité tumorale Gold Nanoparticle Uptake in Tumor Cells: Quantification and Size Distribution by sp-ICPMS . Radiation Enhancer Effect of Platinum Nanoparticles: Experimental in Vitrolimits Andrelevant Physical Chemical Simulation“. Thesis, université Paris-Saclay, 2021. http://www.theses.fr/2021UPASL004.
Der volle Inhalt der QuelleThe use of high-Z nanoparticles to enhance radiotherapy effects has gained momentum over the last decade. Historically, as nanoparticles increase tumor density, they were thought to improve radiation dose by locally increasing the probability of interactions with ionizing radiations. Local dose enhancement is then associated with increased oxidative stress and DNA damage. Therefore, radiosensitization with nanoparticles could impair radioresistance as well as improve therapeutic index. Radiotherapy is a cornerstone of breast cancer treatment. However, mammary tumors are heterogeneous and comprise distinct populations of cancer cells that respond differently to treatments. Cancer stem cells (CSC) and epithelial to mesenchymal transition (EMT) are major factors contributing to cancer cells plasticity, tumor heterogeneity, and escape from programmed cell death (apoptosis). In breast cancer, both CSC and cells undergoing EMT are characterized by the expression of two surface markers CD24 and CD44 (CD24-/low, CD44 high). This work aims to evaluate the efficiency of high-Z nanoparticles of different nature (gold, platinum), different size (from 5 to 35 nm) and different surface charge (positive and negative) as potent radiosensitizer on several breast cancer models of different epithelial or mesenchymal state. As no significant change could initially be observed in vitro following the combination of nanoparticles with radiation compared to radiation alone, I gain insight on the influence of physical, chemical and biological parameters required for characterizing radio-enhancement. Among them, I focused on improving the diffusion of nanoparticles and their internalization in tumor cells. I showed that nanoparticles uptake by breast cancer cells was depending on their mesenchymal state: nanoparticle internalization by cancer cells is dramatically increased in mesenchymal-like cancer cells compared to epithelial-like cells across a panel of several breast cancer cell lines. Importantly this discrepancy was not affected by the charge, size or surface chemistry of the nanoparticles themselves. This strongly suggests a cell-dependent mechanism, in opposition to the current paradigm that nanoparticles uptake is mainly governed by their inherent physical/chemical properties. This study emphasized the importance of membrane and extracellular structures in nanoparticle recognition and preferential interaction with cells. Our results are of peculiar interests as the identification of genes or mechanisms facilitating nanoparticles accumulation into radioresistant cancer cells could further conception of promising therapeutic nanoparticles
Bibin, Lazar. „Simulation 3-D d'anesthésie loco-régionale : neurostimulation et échographie“. Paris 5, 2007. http://www.theses.fr/2007PA05S004.
Der volle Inhalt der QuelleJean, Dit Gautier-Gaudenzi Estelle. „Modélisation du système pelvien de la femme enceinte et simulation d'accouchement : outil analytique et pédagogique“. Thesis, Lille 2, 2018. http://www.theses.fr/2018LIL2S019/document.
Der volle Inhalt der QuelleWe aim at developing a complete 3D numerical model of a parturient pelvic system representing all the anatomical structures of the pelvis such as ligament, muscle and organs. Then we generate a parametric FE model that allows simulating normal and dystocic vaginal delivery.We have developed a parturient pelvic numerical model at different gestational ages, 16, 32 and 38 weeks of gestation, (WG) and in postpartum (2months and 1year) from MRI. The different organs, muscles and ligaments of the pelvic system were segmented in order to generate a complete anatomical 3D model. Starting from this numerical model we studied the changes the muscles and ligaments undergo during pregnancy. Then we performed a Finite Element (FE) model that allows simulation and analysis of the deformations of pelvic anatomical structures under the stress induce by normal and dystocic vaginal delivery. In particular, we investigated the influence of the head size, terms and cephalic orientation and flexion. We particularly studied the structures that play an important role in the stability of the pelvic system.ResultsThe analysis during pregnancy of the US ligaments and levator ani muscle (LAM) reveals some geometrical modification, even then at the beginning of the second pregnancy trimester. This 3D anatomical model help to develop a teaching model for manual removing of the placenta, that could be integrated in a simple physic mannequin. The proof of pedagogical interest of this tool was made by different series of tests, underwent by gynaecolog-obstetrician and midwives. Then we worked with FE simulation of the vaginal delivery. The model developed is parametric. Than mean we can then change different maternal and fetal criteria such as gestational age, fetal head size, orientation and flexion. First place we performed normal vaginal delivery to study the impact of the fetal head descent in the pelvic system, and his stress impact on the different anatomical structures. Then we introduce dystocic element. We can evaluate and localize the strain levels and the most injured areas. Posterior cephalic presentation presents higher injury risk than the anterior one. Maternal geometry at different terms brings equivalent results contrary to the fetal head sizes that have an influence on the strain level and the potential damage induced. We developed pressure and trajectories sensors integrated in a forceps. We can then record an ex-vivo forceps extraction and then integrate all the information in the FE model.ConclusionThis multi-parametric investigation allows us to have a customizable and predictive tool evaluating the potential damages on the pelvis during vaginal delivery. We could then explain, understand and maybe predict some maternal and fetal complications that could happen during vaginal delivery. We can in particular try to explain the perinea injuries during, after and long time after vaginal delivery. This tool can be used to teach the complexity of obstetric
Risser, Fanny. „Études d’un mécanisme enzymatique et d’interactions inter-protéiques au sein de voies complexes de biosynthèse de polycétides Characterization of Intersubunit Communication in the Virginiamycin trans-Acyl Transferase Polyketide Synthase Understanding Intersubunit Interactions in the Enacyloxin Mixed cis- /trans-acyltransferase Modular Polyketide Synthase Insights into a dual function amide oxidase/macrocyclase form lankacidin biosynthesis“. Thesis, Université de Lorraine, 2019. http://www.theses.fr/2019LORR0296.
Der volle Inhalt der QuelleComplex polyketides are secondary metabolites which are produced by a range of different organisms, and which present a broad spectrum of therapeutic activity. The modular organization of the enzymes responsible for their synthesis, the polyketide synthases (PKS), makes them attractive targets for synthetic biology aimed at obtaining new polyketide structures. One of the most promising strategies to date consists in swapping of whole sub-units between different PKS systems. However, the success of this strategy critically depends on understanding and exploiting ‘docking domains’ the protein sequences at the C- and N-terminal extremities of the subunits which are responsible for correctly ordering the polypeptides, and therefore for faithful chain transfer. To increase our knowledge of DDs, we investigated several interfaces in both trans-AT and cis-AT PKSs. This work led notably to the identification of the first family of DDs from trans-AT PKSs, and we were further able to characterize a complete interface formed between two consecutive subunits within the virginiamycin PKS. In addition, we showed that at least one DD of matched pairs is often an intrinsically disordered region (IDR), as this type of interaction motif allows for specific but medium affinity contacts. Indeed, in the enacyloxin hybrid cis-AT/trans-AT PKS which we also investigated extensively, docking at every interface is mediated by a C-terminal IDR. In addition, we demonstrated that multiple structural classes of DD are present within the system, but that variations of the electrostatic ‘code’ within an individual structural class can also be used to ensure specificity. Taken together, these results provide important guidelines for future attempts to deploy DDs in subunit engineering. Another attractive target for synthetic biology are the so-called ‘post-PKS’ enzymes, which chemically decorate the initially-formed structure, and are often essential for their bioactivity. In this context, we studied LkcE, a bi-functional enzyme that catalyzes a rare amide oxidation followed by an intramolecular Mannich reaction to yield the lankacidin macrocycle – both to understand its unusual mechanism and to evaluate its suitability as a general polyketide modifying enzyme. We solved four crystal structures of the enzyme, and characterized it kinetically. Together, our data allowed us to propose a detailed catalytic mechanism for LkcE, involving a large-scale conformational change of the enzyme to bring the substrate into a cyclisation-ready state. Moreover, we showed that LkcE displays a certain tolerance toward its substrate structures, suggesting its usefulness as a general catalyst for cyclisation/ligation reaction in synthetic biology and chemical synthesis
Chabridon, Sophie. „Performances et fiabilite des systemes paralleles et distribues“. Paris 5, 1996. http://www.theses.fr/1996PA05S002.
Der volle Inhalt der QuelleDeyawe, Kongmeneck Audrey. „Investigation des mécanismes d’activation et de couplage du canal potassique voltage-dépendant KV7.1 dans les cardiomyocytes à l’aide de méthodes computationnelles“. Electronic Thesis or Diss., Université de Lorraine, 2020. http://www.theses.fr/2020LORR0175.
Der volle Inhalt der QuelleKV7.1 is a voltage-gated ion channel that open to selectively diffuse K+ ions across the plasma membrane upon membrane depolarization. In the myocardium tissue, KV7.1 channel is co-expressed with the ancillary subunit KCNE1 to generate the IKS current during cardiac action potential. The mutations of KV7.1 and KCNE1that are linked to severe cardiac arrhythmias make KV7.1 channel a major therapeutic target. Each α-subunit of KV7.1 tetramer counts six transmembrane helices (S1 to S6), the first four ones forming the voltage-sensor domain (VSD), and the last two ones forming the pore domain (PD). This channel has a 2-step activation mechanism involving three stable states: resting, intermediate and activated. These conformations can induce pore opening or closure by a process called VSD-PD coupling. Accordingly, the states for KV7.1 channel are Resting/Closed (RC), Intermediate/Open (IO) and Activated/Open (AO). In the presence of KCNE1, the coupling is inhibited in the intermediate state, thus the states for IKS channel are RC, Intermediate/Closed (IC) and AO. Furthermore, the lipid PIP2 (phosphatidylinositol-4,5-bisphosphate) plays a crucial role in the VSD-PD coupling of KV7 channels. Despite the information drawn from both functional and structural studies of KV7.1, the modulation mechanisms of its VSD-PD coupling by KCNE1 and PIP2 remain unclear at an atomistic level. With the help of powerful computational tools, we designed molecular models of Kv7.1 in order to have a better understanding of its function. The study of these models, conducted in collaboration with Pr. Jianmin Cui’s research team (Washington University of Saint-Louis, USA) allowed us to obtain four novel results about the way Kv7.1 opens. Indeed, this joint study revealed a novel VSD-PD coupling mechanism that we conceptualized by a “hand-and-elbow” model likely to occur in all domain swapped (KV1- KV7) channels. The analyses of IKS MD trajectories suggest that KCNE1 disrupts the “hand-and-elbow” model. In addition, the interactions between KCNE1 and PIP2 form a tourniquet around the cytoplasmic region of S6, leading to pore closure in both RC and IC models. Finally, the S6 helix of KV7.1 has a motif SFF (338-340), highly conserved in KV7 family, which forms an unidentified hydrophobic gate in KV7.1 pore. Two of these results were confirmed by in vitro experiments conducted by our collaborators on this channel, which validates the quality of our models for innovative therapeutic research
Moas, Heloire Valeria. „Conception, synthèse et évaluation de nouveaux ligands antagonistes de récepteurs A2a“. Thesis, Lille 2, 2015. http://www.theses.fr/2015LIL2S007/document.
Der volle Inhalt der QuelleAdenosine is a ubiquitous neuromodulator able to regulate many physiological processes and plays an important neuroprotective role in the central nervous system. Its effects are transmitted by four distinct G protein receptor subtypes designated A1, A2a, A2b, and A3. A2a receptors (A2aR) show a restricted distribution, being characteristic of the dopamine enriched areas, the highest concentration being in the caudate-putamen in brain, where it has an important role in neuronal signaling with this region and potential involvement in neurologic disease of extrapyramidal origin.A2a antagonism was shown to be a promising pharmacological target for neurodegenerative diseases such as Parkinson’s disease (PD) and Alzheimer disease (AD). Currently, only three compounds are still in clinical phase for PD treatment. Even if they show good affinities for the receptor, there is still a need for improving their ADME properties by keeping their selectivity towards other adenosine receptors.At the beginning of this project, a Tic-hydantoin derivative was identified as a new ligand with a good affinity for the A2a receptor. Based on the recently published crystalline structure of the A2A receptor complexed with the selective and high-affinity antagonist ZM241385 and a pharmacophoric model, we identified the missing features needed for a good affinity in our molecule. We designed and evaluated in silico many pharmacomodulations around the heterocyclic ring and Tic-guanidin substructure was proposed to present favorable hydrogen bound with Asn253 of the A2a binding site. This structure was obtained after optimization of a new synthetic pathway. Moreover, 1700 molecules were originally designed and evaluated in silico. Among potential interesting families, two of them, quinolizidinones and amino-imidazopyridines were synthesized and evaluated in vitro toward their affinity for A2a receptor and their cytotoxicity towards neuronal cells
Madaoui, Hocine. „Prédiction structurale et ingenierie des assemblages macromoléculaires par bioinformatique“. Paris 7, 2007. https://tel.archives-ouvertes.fr/tel-00553875.
Der volle Inhalt der QuelleThe high-throughput characterization of the protein-protein interactions networks laid the bases for the first interaction maps in all model organisms, including human. In contrast, the structures of the protein assembles are still restricted to a very limited set of interactions. In this work, a specific evolutionary pressure that is exerted at protein interfaces has been revealed. To our knowledge, no such effect had been previously described. Based on this finding, a novel bioinformatic approach, called scotch (surface complementarity trace in complex history) has been developed to predict the structures of protein assembles. Coupled to a docking program, such as scotcher also developed in this work, this approach was shown to predict efficiently the structures of many complexes. This work also focuses on the inhibition of protein interactions by synthetic peptides, rationally designed on the basis of the complex structure. The results obtained for two examples, the asf1 - histone h3/h4 and the gp120 - cd4 complexes emphasize the high interest of rational design of complex interface for the development of novel therapeutic strategies
Audry, Cécile. „Gestion des ressources en situation de crise : étude réalisée avec des étudiants en médecine de 5e annéeApports de le [i. E. = la] simulation“. Montpellier 1, 2011. http://www.theses.fr/2011MON11101.
Der volle Inhalt der QuelleLamblin, Géry. „Modélisation biomécanique 3D des prolapsus génitaux et simulation de leur correction chirurgicale“. Thesis, Lille 2, 2017. http://www.theses.fr/2017LIL2S032/document.
Der volle Inhalt der QuelleGenital prolapse is a frequent female functional pathology that can have strong impact on quality of life; it is today a real public health issue. Surgical treatment of the various stages of cystocele is a current challenge. We developed an innovative 3D numerical model using the Finite Elements method, to enable simulation of the various surgical techniques. The model also allowed validation of our surgical hypotheses and provided some answers to outstanding questions in cystocele surgery. The first of my PhD studies allowed me to make a complete review of the anatomical pelvic organ support structures involved in prolapse, and to distinguish certain anatomic theories relating clinical expression to specific anatomic lesions. The various theories are actually quite close and complementary, but differ in terms of the mechanism implicated. The second study involved designing a 3D numerical biomechanical model of the pelvic floor, based on Finite Elements analysis coupled to dynamic MRI. The model allowed me to assess the various theories of pelvic organ suspension, and to design simulations of cystocele mobility. The model provided better understanding of the anatomic structures involved in prolapse. The third study involved designing a 3D numerical pathologic model based on data for patients with grade ≥ 3 cystocele. The model enabled analysis and assessment of the impact of the various surgical correction techniques and fixation zones on organ mobility. Although the results have not been validated clinically, the study contributed to the scientific literature on the importance of mesh reinforcement in the management of cystocele. Comparison between the various techniques (sacrocolpopexy, vaginal mesh suspension, sacrospinous fixation) using the POP-Q points found that point Ba was better corrected by sacrocolpopexy than sacrospinous fixation or vaginal mesh suspension. For sacrospinous fixation, the further it is performed from the sciatic spine, the better the apical correction of point C but the poorer the correction of point Ba. These findings could be used to improve surgical correction techniques and standardize practice. Thus, our 3D numerical cystocele model could contribute to selecting the surgical technique for correction of the cervix and anterior vaginal wall. The Finite Elements model of the pelvic system provides better understanding of the mechanisms underlying surgical correction of cystocele and the vaginal apex. It could also enable the results of prolapse surgery to be predicted, adapting technique to the individual patient by preoperative simulation. Simulation provides original and interesting information on mobility in prolapse. The present simulation results obviously need future assessment in comparison with clinical practice. In conclusion, simulation and the implementation of a 3D numerical model of pelvic mobility now allows better understanding of the mechanisms underlying pelvic statics disorder, with simulation of pathological pelvic mobility and of prolapse surgery procedures
Laurent, Xavier. „Etude in silico du complexe CD1d/Ag : bases moléculaires de l’orientation de la réponse immunitaire des cellules iNKT“. Thesis, Lille 2, 2014. http://www.theses.fr/2014LIL2S031/document.
Der volle Inhalt der QuelleDevelopment of new ligands able to switch invariant Natural Killer T (iNKT) cells toward an immunostimulant Th1 or an immunoregulative Th2 profile is a great challenge that can lead to new therapeutic opportunities in the treatment of various auto-Immune diseases or cancers. In this context, understanding the polarizing effect of iNKT ligands is of a major interest. We hypothesized that the intensity and nature of the biological response could depend on the stability of the CD1d-T Cell Receptor (TCR) interactions under the influence of the antigen which could modulate the shape of CD1d. Thus, our goal was to study the impact of iNKT ligands on the structure of the CD1d molecule and find clues to help design Th1/Th2 selective ligands.Using structure-Activity relationships, docking and molecular dynamic analyzed by a mix of classical and in house tools, we compared the structural behavior of the human and mouse CD1d molecule loaded with different ligands inducing Th1 or Th2 immune response profile. From the analysis of our molecular dynamics trajectories, it appears that there are noticeable differences in the behaviour of human and mouse CD1d molecules, mainly caracterized by changes at the inter-Helix distance and an increase ligand mobility for human systems.One major result is the identification of a specific conformational state of the ligand sugar group which could be correlated, in the present study, to the biological Th2 biased response. The different methods and combinations of ligand and protein descriptors used to analyze the dynamics of the binary complexes provide a structural basis for predicting the very different dynamical behaviors of ligands in CD1d and might aid in the future design of new iNKT modulators
Bourget, Philippe. „Contribution à la maitrise des thérapeutiques chez la femme enceinte : à propos de 6 médicaments majeurs : conception d'un outil expert d'analyse pharmacocinétique : pharmac BD® 1.0“. Paris 11, 1991. http://www.theses.fr/1991PA114828.
Der volle Inhalt der QuelleDupont, Clément. „Photodynamic therapies of high-grade gliomas : from theory to clinical perspectives“. Thesis, Lille 2, 2017. http://www.theses.fr/2017LIL2S034/document.
Der volle Inhalt der QuelleGliomas are the most common primary brain tumors in adults. Among them, glioblastoma (GBM) represents the most frequent primary brain tumor and have the most dismal prognosis. Its annual incidence is about 3 to 5 cases for 100,000 persons (about 3000 news cases each year in France). Median survival varies between 11 to 13 months according the extent of tumor resection.The standard of care includes surgery and is followed by radiation therapy and chemotherapy. Maximal resection is expected to delay recurrence. Despite of using intraoperative photodynamic diagnosis, or fluorescence guided resection (FGR), which improves the extent of resection, relapse still occurs in these resection margins in 85% of cases.Alternatives therapies have to be developed to enhance patients’ overall survival. In this context, Photodynamic Therapy (PDT) seems relevant. PDT is based on the synergy of three parameters: a photosensitizing molecule, the photosensitizer (PS) that concentrates preferentially into the tumor cells, laser light and oxygen. Laser light induces a reaction between the PS and the oxygen of the cell. This reaction produces highly cytotoxic molecules (including singlet oxygen) and leads to death of tumor cells. Two treatment modalities are investigated: interstitial PDT (iPDT) or intraoperative PDT.The main goal of this thesis is to provide technological tools to develop the PDT for GBM treatment. Thus, the two treatment modalities have been investigated.When tumor resection is non-achievable (about 20% to 30% of cases), iPDT may be preferred. This modality aims to insert optical fibers directly into the target to illuminate tumor tissues. Thus, simulation of light propagation in brain tissues is required to plan the location of optical fibers. Considered as reference method, a Monte-Carlo model accelerated by graphics processing unit was developed. This model computes the light propagation emitted by a cylindrical diffusor inside heterogeneous media. Accuracy of the model was evaluated with experimental measurements. The acceleration provided by the parallelization allows its use in clinical routine.The iPDT has to be planned using a Treatment Planning System (TPS). A proof of concept of a TPS dedicated to the stereotactic iPDT treatment of GBM was developed. This software provides basic tools to plan the stereotactic insertion of cylindrical diffusors in patient’s brain and to compute the associated dosimetry. The stereotactic registration and the dosimetry computation’s accuracy were evaluated with specific methodologies.When tumor resection is achievable, the intraoperative PDT may be applied early after the FGR. It takes advantage of the presence of the PS (the protoporphyrin IX) used for FGR purpose and that is already concentrates into the tumor cells. Thus, the proposed treatment strategy fits into the current standard of care. A medical device was designed to fit to the resection cavity and illuminate homogeneously the cavity’s margins. The device is constituted of two parts: a trocar coupled to an inflatable balloon and a fiber guide developed in the ONCO-THAI laboratory allowing to insert the light source. Specific methodologies were developed to calibrate and assess the device in terms of mechanical properties and dosimetry. The calibration process leaded to a transfer function that provides fast, robust and easy treatment duration prescription to induce a PDT response in cavity margins. Furthermore, a comprehensive experimental design has been worked out prior to the clinical trial that evaluate the safety of the procedure
Platkiewicz, Jonathan. „Dynamique de l'excitabilité neuronale : approches théorique et numérique“. Phd thesis, Université René Descartes - Paris V, 2010. http://tel.archives-ouvertes.fr/tel-00612602.
Der volle Inhalt der QuelleBano, Jordan. „Modélisation et correction des déformations du foie dues à un pneumopéritoine : application au guidage par réalité augmentée en chirurgie laparoscopique“. Thesis, Strasbourg, 2014. http://www.theses.fr/2014STRAD010/document.
Der volle Inhalt der QuelleAugmented reality can provide to surgeons during intervention the positions of critical structures like vessels. The 3D models displayed during a laparoscopic surgery intervention do not fit to reality due to pneumperitoneum deformations. This thesis aim is to correct these deformations to provide a realistic liver model during intervention. We propose to deform the preoperative liver model according to an intraoperative acquisition of the liver anterior surface. A deformation field between the preoperative and intraoperative models is computed according to the geodesic distance to anatomical landmarks. Moreover, a biomechanical simulation is realised to predict the position of the abdomino-thoracic cavity which is used as boundary conditions. This method evaluation shows that the position error of the liver and its vessels is reduced to 1cm
Boutillier, Johanna. „Contribution à la compréhension et à la modélisation des effets lésionnels sur le thorax des ondes de choc aériennes“. Thesis, Strasbourg, 2017. http://www.theses.fr/2017STRAD003.
Der volle Inhalt der QuelleWith the increasing number of bombing attacks and armed conflicts, the risk of thoracic injuries caused by the blast threat is worsen, without knowing the efficiency of the current individual chest protection systems impacted by such a threat. This research, combining experiments and numerical simulations, dealt with the physics at play from the detonation of an explosive charge and the injury outcomes. One of the first objectives was to understand the different physical phenomena involved in the propagation of the shock wave in the open field. The huge set of data acquired allowed the development of simple tools for the determination of the blast characteristics as well as a robust numerical approach under LS-DYNA. The next objective was to study the interaction of shock waves with targets of simple geometries and different compositions. In addition to the numerical validation of the fluid-structure interaction and of the FEM of the structures, the analysis of the experimental data acquired allowed to determine possible candidates for the definition of a thoracic injury criterion. Finally, tests on biological post-mortem reactors have been carried out, which enabled to obtain the kinematic response of the swine’s thorax under blast. All this work has led to improvements and promising tools for the evaluation and the improvement of chest protection systems in the near future. The proposed tools should be used to limit the risks to this threat which has gained in importance in recent years
Rosati, Elise. „Outils d'aide à la conception pour l'ingénierie de systèmes biologiques“. Thesis, Strasbourg, 2018. http://www.theses.fr/2018STRAD008/document.
Der volle Inhalt der QuelleIn synthetic biology, Gene Regulatory Networks (GRN) are one of the main ways to create new biological functions to solve problems in various areas (therapeutics, biofuels, biomaterials, biosensing). However, the complexity of the designed networks has reached a limit, thereby restraining the variety of problems they can address. How can biologists overcome this limit and further increase the complexity of their systems? The goal of this thesis is to provide the biologists with tools to assist them in the design and simulation of complex GRNs. To this aim, the current state of the art was examined and it was decided to adapt tools from the micro-electronic field to biology, as well as to create a Genetic Programming algorithm for GRN design. On the one hand, models of diffusion and of other various systems (band-pass, prey-predator, repressilator, XOR) were created and written in Verilog A. They are already implemented and well-functioning on the Spectre solver as well as a free solver, namely NgSpice. On the other hand, the first steps of automatic GRN design were achieved. Indeed, an algorithm able to optimize the parameters of a given GRN according to a specification was developed. Moreover, Genetic Programming was applied to GRN design, allowing the optimization of both the topology and the parameters of a GRN. These tools proved their usefulness for the biologists’ community by efficiently answering relevant biological questions arising in the development of a system. With this work, we were able to show that adapting microelectronics and Genetic Programming tools to biology is doable and useful. By assisting design and simulation, such tools should promote the emergence of more complex systems
Congnard, Florian. „Méthodologie et physiopathologie des mesures de pressions artérielles périphériques chez le sujet sain : aspects cliniques, méthodologiques et pédagogiques“. Thesis, Angers, 2017. http://www.theses.fr/2017ANGE0049/document.
Der volle Inhalt der QuelleThe measurement of ankle to brachial pressure index (ABPI) is a simple and non-invasive diagnostic tool for detecting arterial involvement of the lower limbs. If the methodology and interpretation of this index have been standardized, there remain some discrepancies about some aspects of its measurement. Thus, the present thesis reports the investigations of three of these aspects. First, the objective was to study the physiological relationship between ABPI and age among healthy and physically active subjects. The results show a positive relationship. This trend is consistent with structural modifications of arterial wall with ageing. Second, our aim was to investigate the use of automatic blood pressure measurement tools for the calculation of ABPI during the recovery of a maximal physical exercise. We found that the use of anoscillometric blood pressure device allowed to obtain a faster postexercise ABPI faster than a manual recording and also to reduce the standard error of the measurement. Finally, we discussed the learning strategies of this peripheral vascular measurement. Indeed, it appears that the measurement of arterial systolic blood pressure at the ankle (ASBPa) is largely under-taught compared to the humeral measurement. The purpose was to objectively assess, by a simulator, the effect of an additional practical and pedagogical intervention on the ability of novice students to perform ASBP a measurement. The results suggest that a one-hour practical learning allows to significantly reduce the measurement error but is not sufficient to harmonize all of the measurement parameters according to the measurement standards