Academic literature on the topic 'Conception innovante – Dissertation universitaire'
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Dissertations / Theses on the topic "Conception innovante – Dissertation universitaire":
Briard, Tristan. "Des données captées aux créations de valeurs : Proposition d’une méthode outillée pour structurer la conception amont des produits intelligents et connectés." Electronic Thesis or Diss., Paris, HESAM, 2023. http://www.theses.fr/2023HESAE095.
Recent advances in information and communication technologies and data science have led to the development of smart connected products. These products have new capabilities that create value for both the user and the manufacturer. These developments are leading to a major paradigm shift. To take full advantage of the potential of smart connected products, manufacturers need to adopt new processes, especially in the design phase. Indeed, the choice of data that can be captured by the product at the design stage defines the potential value creation for the rest of its life cycle. The aim of this thesis is therefore to formalise a methodological structure to guide designers in the integration of value creation based on captured data. In order to propose a relevant and effective method, we first explore the challenges related to design and captured data. Based on the challenges identified, a method is then constructed. It is structured in two phases, each supported by a dedicated tool. The first phase is a creativity phase that systematically generates potential value creation based on captured data. The second phase is a decision-making phase in which the previously generated value creations are systematically ranked according to sustainability criteria. Experiments have validated the relevance and effectiveness of the proposed methodology. Through the method and its tools, this thesis work contributes to scientific and industrial research supporting the paradigm shift brought by digital technologies in product design
Hertault, Adrien. "Conception et évaluation d’un stent actif pro-cicatrisant basé sur la polydopamine, un polymère biocompatible et bioinspiré." Thesis, Lille 2, 2019. http://www.theses.fr/2019LIL2S031.
Introduction: In-stent restenosis (ISR) is induced by an uncontrolled smooth muscular cells (SMC) proliferation after bare metal stent (BMS) implantation. It is associated with recurrence of symptoms and additional health costs. Drug-eluting stents have demonstrated efficiency on ISR but induce a high risk of late acute thrombosis due to a delayed struts reendothelialization. Polydopamine (PDA), a biocompatible polymer inspired from mussels byssus, has been reported to promote endothelial cells (EC) and inhibit SMC proliferation in-vitro, thus suggesting a potential pro-healing effect on the vascular wall. Furthermore, polydopamine expresses amine, catechol and quinone functions on its surface and can be used as an anchor for another therapeutic agent. This study aimed at 1) evaluating the impact of a PDA-coated stent on in-stent restenosis (ISR), 2) designing a vascular stent with a potential additional pro-healing drug, hemin, immobilized via the PDA layer.Methods: In the first part of this study, PDA coatings were obtained by dip coating of cobalt-chromium disks or stents in a dopamine solution. Disk samples were used to evaluate biocompatibility and hemocompatibility. The pro-healing potential was investigated in-vitro by seeding human EC and SMC on the different samples. In-vivo experimentations were conducted to assess the pro-healing effect in a rat model. ISR was evaluated in optic microscopy with quantification of the neointima/media (n/m) ratio after eosin/hematoxillin coloration. Quality of the struts reendothelialization was assessed with transmission electron microscopy (TEM). Molecular pathways involved in a potential pro-healing effect were investigated with western blot analyses.In the second part of this work, PDA-coated surfaces were modified with polyethylenimine (PEI) to enhance the expression of amine functions. This modified coating was characterized and cytocompatibility was assessed in-vitro. This modified surface was used to immobilized hemin, a therapeutic agent, on the sample surfaces. Functionalized surfaces were characterized, and presence of the therapeutic agent was assessed and quantified. The potential healing effect of the hemin-stent was evaluated in-vitro and in-vivo.Results: PDA surfaces demonstrated a pro-healing effect in-vitro compared to bare chromium-cobalt. PDA stents demonstrated a significant reduction in ISR compared to bare metal stents (ratio n/m = 0.48 (+/- 0.26) versus 0.83 (+/- 0.42), p<0.001) in the rat model. TEM analyses confirmed the presence of neointima surrounding the struts in each group and revealed a thinner neointima layer in the PDA-stent group compared to BMS, with similar ultrastructures of the cells facing the arterial lumen. Western blot analyses identified a trend to an increased activation of p38 MAPK phosphorylation and its anti-proliferative effects on vascular SMC which could explain the results observed in the histomorphometric analyses.Immobilization of PEI was achieved through Michael addition and Shift base reaction on PDA coatings, and successfully enriched the surfaces with amino groups without decreasing cytocompatibility. Hemin was successfully grafted on the PDA-PEI surfaces via amide bounds (approximately 10ng of hemin per cm²). Hemin-coated surfaces demonstrated no superiority in-vitro or in-vivo to PDA alone.Conclusion: The expected pro-healing effect of PDA-coating on the arterial wall seems to be confirmed in this in-vivo model. This biocompatible polymer could intrinsically limit in-stent restenosis. Additionally, it also offers the possibility to immobilize many relevant drugs on its surface through amine functions providing potential synergistic effects
Mogrovejo, Valdivia Alejandra. "Conception et évaluation d'un pansement à libération de deux principes actifs pour le traitement des plaies chroniques." Thesis, Lille 2, 2018. http://www.theses.fr/2018LIL2S046.
Chronic wounds present a risk of infection, delaying the healing process and leading to severe pain. Chronic wounds represent a public health problem that generates high costs. Silver dressings are widely used to treat wounds already infected or with a risk of infection. Nevertheless, the toxic effect of silver toward fibroblasts and keratinocytes generates a perception lack of efficacy and cost effectiveness, and question their effectiveness as well as its safety. The goal of this work was to design a wound dressing releasing two active ingredients: a silver salt to treat the infection and ibuprofen to relieve the pain. The dressing was coated by a layer-by-layer (L-b-L) system to slow down silver diffusion into the wound and at the same time provide a moist environment to the wound. First, a nonwoven polyester textile was functionalized by chitosan or by β-cyclodextrin polymer, both crosslinked with citric acid under curing conditions to form a thermofixed negatively charged layer at the surface textile to then loaded silver onto the textile. Next, a L-b-L system was built on the support by alternating self-deposition of CHT as cationic polyelectrolyte and cyclodextrin polymer as anionic polyelectrolyte. A curing process was applied to stabilize the L-b-L system. L-b-L system showed a linear evolution of the weight gain in relation to number of layers formed. Loaded silver and ibuprofen reached up to 240 μg/cm2 and 200 μg/cm2 respectively. Silver was released up to 3 μg/cm2 after 3 days in PBS under static conditions, and ibuprofen was released up to 6 hours under the same parameters. Biological studies proved the dressing cytocompatibility using human lung normal cell lines (L132). In vitro microbiological evaluation showed greater antibacterial activity of the dressing against S. aureus and E. coli. Finally, a preliminary in vivo study was performed in C3H/HE mice with a wound infected by E. coli. The dressings tested were applied to the wounds and were maintained for 3 days. Only the free silver-dressing (negative control) showed a colonization by E. coli
Luu, Duc-Nam. "Proposition et formalisation d’un modèle méthodologique pour la mise en place d’une stratégie d’éco-conception ainsi que des outils de déploiement pour son implémentation. Application au domaine de la pharmaceutique." Electronic Thesis or Diss., Paris, HESAM, 2023. http://www.theses.fr/2023HESAE033.
Environmental issues take a major place in our modern societies. Human activity contributes to the degradation of the environment and manufacturers have the duty to limit the impact of the solutions they offer and put on the market. Eco-design is one of the approaches of Design for Sustainability which makes it possible to integrate environmental aspects, during the development phases. The penetration of its practices within industrials requires vertical and horizontal integration. Horizontal integration concerns the strategic, tactical and operational aspects while horizontal integration focuses on the aspects of cultural change and human factors. This doctoral thesis focuses on the integration of eco-design within a multinational pharmaceutical company. The objective of the project was to formalize the concepts for its integration in the pharmaceutical industry in order to support the transition of internal eco-design practices in this sector. The variety and complexity of eco-design aspects, as well as both the technical and organizational challenges of the pharmaceutical industry must be taken into account in order to provide a coherent transition approach. The experiments for this work were carried out with a partner, an international pharmaceutical industry, in collaboration with the Arts et Métiers, Paris campus. The work carried out has made it possible to lay the foundations of an eco-design integration model within the pharmaceutical industry, with associated support tools
Assailly, Coralie. "Conception et évaluation d'inhibiteurs multivalents de sialidases bactériennes." Thesis, Nantes, 2020. http://www.theses.fr/2020NANT4057.
Sialidases (SA) are expressed by numerous viruses, bacteria and parasites. The catalytic domain (CAT) of bacterial SA is often flanked with a lectinic domain (CBM) that allows the enzyme to anchor to a sialoside surface for increasing its catalytic efficiency. In this work, we designed multivalent thiosialosides targeting both the CAT and CBM domains of SA. The inhibitory activity of the designed sialo-clusters was evaluated on pathogenic SA from S. pneumoniae (NanA), V. cholerae (VcSA) and T. cruzi (TcTS). Strong synergistic effects were observed between NanA and a synthetic polythiosialoside, where each grafted sugar unit has an inhibitory potency up to 3000 times higher than a reference monovalent thiosialoside. An in-depth study of the binding affinity of the multivalent thiosialosides for NanA and the truncated NanA CAT and NanA CBM domains was performed by surface plasmon resonance and by a biochip assay. Insight were provided in the binding mode operating. Then, we developed multivalent compounds based on a more potent inhibitor of the CAT domain, the 2-deoxy-2,3-dehydro-N-acetylneuraminic acid (DANA). Some poly-DANA showed inhibitory levels of the enzymatic activity in the subnanomolar range when assessed against NanA, NanA CAT or the SA from the commensal bacterium B. thetaiotaomicron (BtSA). Binding assays, molecular modeling studies, and crystallographic experiments suggest that this synergistic interactions probably occurs exclusively in the CAT and not the CBM domain. Altogether, these results suggest the interest of using the concept of multivalency to strongly inhibit the binding potency, and the catalytic activity of pathogenic SA
Maiguy-Foinard, Aurélie. "Prévention des événements indésirables médicamenteux associés à la perfusion en anesthésie-réanimation : évaluation de l'impact de dispositifs médicaux de perfusion innovants." Thesis, Lille 2, 2014. http://www.theses.fr/2014LIL2S017/document.
Intravenous (IV) infusion is a common medical act in clinical wards, although not without risk. Many factors affect drug delivery rate (or drug mass flow rate), especially medical devices used to administer one or more drugs. By their very features, these devices may generate more or less significant variations in drug mass flow rate during infusion.The first part of this work consisted in analysing published literature dealing with the impact of medical devices on drug mass flow rate when delivered intravenously. This systematic review revealed mainly in vitro studies on all factors likely to alter the flow rate or concentration of the drug infused.The first stage of our experimental work is dedicated to preventing hazardous disturbances in the mass flow rate of the drug solution infused intravenously to the patient. It showed in vitro the ability of a new multi-lumen infusion access device with a very low internal volume (Multiline-8, Doran International, France) to prevent such disturbances in drug delivery in the context of multi-infusion therapy and when interrupting and resuming carrier fluid flow. The second stage demonstrated in vitro the impact of infusion set characteristics on the accuracy of morphine doses in patient-controlled analgesia. The use of a low dead space volume Y-set significantly improved the accuracy of the morphine dose delivered during bolus and reduced morphine infusion during lockout intervals. Thus, the use of infusion devices with a very low internal volume minimises variations in drug mass flow rate and consequently, clinical impact.The second part of our work focused on the prevention of drug incompatibilities when several treatments are administered simultaneously. The first task accomplished on this topic showed in vitro the ability of multi-lumen infusion access devices to prevent the occurrence of physicochemical incompatibility between two drugs known to be incompatible (furosemide/midazolam). Our results indicate that three factors impact on physical compatibility between drugs: drug concentration, carrier flow rate and the design of the infusion device. Our main hypothesis is that fluid dynamics differ according to infusion devices which modify contact time between the two drugs and saline. The second task was an in vitro quantification of drug loss in the case of drug incompatibility using the example of furosemide and midazolam. Our study revealed that physical incompatibility between two drugs can lead to a significant reduction in drug delivery to the patient, even in the absence of visible particles. Indeed, furosemide precipitation resulting in the formation of visible and/or sub-visible particles led to a drug loss to the patient estimated at between 10% and 15% when midazolam was present. Preventing incompatibilities is a major challenge to ensure the safety and effectiveness of injectable drugs.The results of the whole of our in vitro studies must be validated in a clinical setting to determine the extent to which the choice of device affects the efficiency and safety of IV therapeutics administered to the patient
Bolteau, Raphaël. "Conception, synthèse et évaluation pharmacologique d’antagonistes des récepteurs A2A et de ligands duaux ciblant les récepteurs A2A et mGlu5." Thesis, Lille 2, 2020. http://www.theses.fr/2020LIL2S006.
The past fifty years have been marked by the breakthrough of neurodegenerative diseases such as Alzheimer’s. Unfortunately, only symptomatic treatments are available. Furthermore, facing this multifactorial disease, the search for new and innovative therapeutic targets becomes a major challenge. Among these targets, the adenosine A2A receptor (A2AR) has been the subject of much research in recent years. Indeed, it has been shown that A2AR antagonists such as caffeine improve memory performance as it reduces β-amyloid deposits and Tau-phosphorylation. Though several A2AR antagonists have reached clinical trials, current research efforts are focused on developing new antagonists with relevant ADME properties. On the other hand, negative allosteric modulators of the metabotropic glutamate receptor 5 (mGluR5) also play an important role in the pathological conditions associated with Alzheimer’s disease. It has been found that blocking the activity of mGlu5 reduces the neurotoxicity and synaptoxicity of the amyloid peptide in vitro but also in vivo. Based on a molecular modeling-guided design, we developed new A2AR antagonists with quinazoline and benzofuran as central scaffold and a dual ligands strategy targeting both A2A and mGlu5 receptors. Hit-to-lead optimization has led to nanomolar affinity compounds for A2AR and a new co-crystallized structure. Among them, some hit compounds have been identified with micromolar affinities towards mGluR5
Bollier, Melanie. "Conception et synthèse de purines substituées en positions C8 et N9 en tant qu'antagonistes potentiels du récepteur NOD1 en vue de limiter les lésions d'ischémie-reperfusion hépatique." Thesis, Lille, 2018. http://www.theses.fr/2018LILUS058.
In Europe, liver transplantation is facing a lack of donation and the few available organs are threatened by the ischemia-reperfusion (I-R) phenomenon. Recently, the LIRIC revealed the role of NOD1, a cytoplasmic pattern recognition receptor, in this phenomenon. The NOD1 receptor is an intrinsic central regulator of polymorphonuclear neutrophils (PMNs) migration and phagocytic capacities. The NOD1 receptor regulates also the interaction between PMNs and hepatocytes and consequently the PMN-induced hepatocyte lysis. It is interesting to note that in an I-R model, nod1-/- mice are protected from hepatic I-R injuries. In this model, mice treated with ALINO73, a NOD1 signaling pathway inhibitor from the literature, analogue of SB711, are also protected from hepatic I-R injuries. These results suggest that the development of NOD1 antagonists is a potential therapeutic solution to minimize hepatic I-R injuries.A 3D virtual model of the NOD1 LRR domain, the recognition domain, was developed in the LIRIC. Using this model and a rational design strategy, a new chemical series as potential NOD1 antagonist was identified, the arylimidazole series and more exactly, a series of C8 and N9 disubstituted purinergic compounds.These potential NOD1 antagonists have been synthesized using two strategies: one by imidazole annulation in one or two steps, another one starting from adenine. A total of fifty-seven final compounds were obtained with moderate to good yields. Part of these compounds was evaluated using an in vitro assay to identify their capacity to block NOD1-mediated NFκB signaling pathway.These synthesized compounds will also be evaluated by surface plasmon resonance (SPR) and thermophoresis to determine their affinity for NOD1. The identified NOD1 antagonists will be evaluated in ex vivo and in vivo models after determining their ADME-Tox properties in vitro
Gay, Marion. "Conception, synthèse et évaluation de composes interagissant avec la dégradation des protéines pour le traitement de maladies neurodégénératives." Thesis, Lille 2, 2015. http://www.theses.fr/2015LIL2S056.
Two physiopathological processes are involved in Alzheimer’s disease: the senile plaques (amyloid pathology) consisting of Aβ peptide aggregates and neurofibrillary tangles (Tau pathology) caused by the accumulation of hyper and abnormal phosphorylated Tau protein. Currently, only symptomatic treatments are available. Therefore, the development of curative drugs is a very active research field. Previous work in the laboratory led to the discovery of a family of compounds (MSBD) which lead-compounds are active on both pathologies of the Alzheimer’s disease. A drug candidate, AZP2006, emerged from that research and is currently in phase 1 clinical trials. Investigations on the identification of the biological target of AZP2006 led to p97/VCP protein, a target that has attracted considerable attention over the last few years for the treatment of neurodegenerative diseases (NDD).This PhD thesis deals with three main aspects:1) Study of the interactions between p97/VCP and developed compounds. STD-NMR studies have confirmed the interaction between AZP2006 and p97/VCP, though these preliminary results have to be confirmed by complementary techniques. AZP2006-based chemical probes were designed and synthesized to develop a FRET-based binding assay in order to get a more quantitative characterization of the binding.2) Development of new p97/VCP ligands. Based on previous ligands developed in the laboratory, a pharmacophore model was built. Subsequent, virtual screening and de novo design led to the identification of several chemical structures. Four families were synthesized and tested in vitro showing a good effect on Aβ peptides secretion and APP metabolism. These compounds are being tested on Tau hyperphosphorylation. The binding to p97/VCP was confirmed by STD-NMR.3) Development of multi target compounds acting on both the two pathology of Alzheimer disease and acetylcholinesterase (AChE). Activities of these compounds were validated in vitro (inhibition of AChE, Aβ peptides secretion, APP metabolism and Tau). In vivo, one of the compounds increased cognitive performance in two mice transgenic models.The results obtained during this PhD confirmed the therapeutic potential of p97/VCP in NDD and proposed new structures for their treatment
Sturbaut, Manon. "Conception, synthèse et évaluation de ligands de TEAD pour le traitement des cancers." Thesis, Lille 2, 2019. http://www.theses.fr/2019LIL2S049.
The Hippo signaling pathway is an important player in the control of organ size, cell proliferation, differentiation, and apoptosis. It consists of kinases cascade which regulate the phosphorylation of coactivators YAP and TAZ in order to control their nuclear import and their interaction with TEAD1-4 (Transcriptional enhancer associate domain). The formation of the YAP/TAZ-TEAD1-4 complexes leads to the expression of genes involved in cell adhesion, migration, proliferation, differentiation, apoptosis, and senescence. YAP, TAZ and TEAD are overexpressed in several cancers and targeting these YAP/TAZ-TEAD complexes appears as an innovative strategy for the cancer treatment.The available crystal structures of YAP/TAZ-TEAD1-4 complexes show three interfaces between both proteins, two of them are essential for maintaining the protein-protein interaction. In addition, TEAD1-4 possesses an internal hydrophobic pocket containing a cysteine which can be S-palmitoylated or myristoylated. This acylation seems to be important for the stability of the protein and the loss of this post-translational modification affects the YAP/TAZ-TEAD interaction. Therefore, TEAD1-4 present differents druggables sites which can be targeted.From previous results, we have prepared three series of molecules. In a first series, we examplified a compound which was previously identified through a virtual screening against interface 3. Compounds of the second series were found to be ligands of interface 2 and revealed the existence of a unexpected crytic site. The third series of molecules specifically targeted the internal pocket of TEAD. TEAD2 crystals were soaked with the new synthesized molecules and seven co-crystals with a satisfactory resolution were obtained. The affinity of some relevant compounds for TEAD2 was measured by surface plasmon resonance and microscale thermophoresis. Finally, the biological activity of our compounds was evaluated on HEK293T cells (TEAD-luciferase reporter plasmid) and MDA-MB-231 cells (protein expression of target genes)