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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

Transporto priemonių numerių atpažinimo algoritmų analizė bei universalios atpažinimo sistemos teorija / License plate localization and recognition algorithms and general lpr theory

Girjotas, Andrius 02 July 2014 (has links)
Automatinis transporto priemonių registracijos numerio atpažinimas atlieka svarbų vaidmenį daugelyje programinių paketų, taikomų tiek valstybinėse institucijose, tiek ir privačiose kompanijose, kuriuose yra naudojamos įvairios atpažinimo algoritmų technologijos. Tačiau net ir dabar neįmanoma sukurti idealiai veikiančios sistemos, kuri palieka laisvę efektyviausių algoritmų paieškai. Šio tiriamojo darbo tikslas yra išanalizuoti alternatyvius automobilio numerio lokalizacijos ir kitų atpažinimo etapų algoritmus, jų efektyvumą bei adaptyvumą. Analizė atliekama juos realizuojant ir atliekant tyrimus su testiniais duomenimis bei iš jų gautais rezultatais. Iš realizuotos alternatyvių atpažinimo algoritmų sistemos gauti rezultatai parodė, kad kiekviena atpažinimo proceso grandis yra jautri įvairiems faktoriams, kurių kitimas lemia tarpinių bei galutinių rezultatų variaciją. / Automatic license plate recognition plays an important role in numerous applications and a number of techniques have been proposed for public institutions or private companies. However, even now it is impossible to design a perfect and operational recognition system. It still leaves a space for creativity and research of the most effective algorithms. The main objective of this dissertation is to analyze alternatives of licese plate localization and other stages of recognition, their efficiency and adaptability. Selected means of this research are such as implementation of algorithms, analysis of testing data and test results. Every stage of recognition process is extremely sensitive to different factors which determinate variation of transitional and final results. This was proven by analysis of alternative algorithms functionality.
2

Transporto priemonių numerių atpažinimo algoritmų analizė bei universalios atpažinimo sistemos teorija / License plate localization and recognition algorithms and general lpr theory

Kazlauskas, Tomas 02 July 2014 (has links)
Automatinis transporto priemonių registracijos numerio atpažinimas atlieka svarbų vaidmenį daugelyje programinių paketų, taikomų tiek valstybinėse institucijose, tiek ir privačiose kompanijose, kuriuose yra naudojamos įvairios atpažinimo algoritmų technologijos. Tačiau net ir dabar neįmanoma sukurti idealiai veikiančios sistemos, kuri palieka laisvę efektyviausių algoritmų paieškai. Šio tiriamojo darbo tikslas yra išanalizuoti alternatyvius automobilio numerio lokalizacijos ir kitų atpažinimo etapų algoritmus, jų efektyvumą bei adaptyvumą. Analizė atliekama juos realizuojant ir atliekant tyrimus su testiniais duomenimis bei iš jų gautais rezultatais. Iš realizuotos alternatyvių atpažinimo algoritmų sistemos gauti rezultatai parodė, kad kiekviena atpažinimo proceso grandis yra jautri įvairiems faktoriams, kurių kitimas lemia tarpinių bei galutinių rezultatų variaciją. / Automatic license plate recognition plays an important role in numerous applications and a number of techniques have been proposed for public institutions or private companies. However, even now it is impossible to design a perfect and operational recognition system. It still leaves a space for creativity and research of the most effective algorithms. The main objective of this dissertation is to analyze alternatives of licese plate localization and other stages of recognition, their efficiency and adaptability. Selected means of this research are such as implementation of algorithms, analysis of testing data and test results. Every stage of recognition process is extremely sensitive to different factors witch determinate variation of transitional and final results. This was proven by analysis of alternative algorithms functionality.
3

Model dopravních situací / Traffic situations model

Krampoťák, Štefan January 2012 (has links)
This master thesis deals with analyze of camera system in real traffic, using these system and realization of traffic situation model. Result of this work is fully functional model of traffic situation, which shows the capability of these camera systems in real traffic. It consists of two basic parts, the first is physical model of traffic with semaphore and second part is control program with algorithm for detection of traffic offences. The system contains speed measurement and red light violation. Model has capable of control the speed of cars, control semaphores and configure cameras.
4

Autophagie comme cible thérapeutique potentielle pour le syndrome de Sjögren / Autophagy as a potential therapeutic target for Sjögren's syndrome

Li, Baihui 13 September 2017 (has links)
Le syndrome de Sjögren (SS) est l'une des maladies autoimmunes (MAI) systémiques les plus fréquentes chez l’Homme. Cette maladie est caractérisée par une infiltration lymphocytaire dans les glandes exocrines conduisant à des symptômes dits de « yeux secs » et à la bouche sèche. Il n’existe actuellement aucun traitement curatif pour cette maladie. Le peptide P140 a été démontrée comme un outil thérapeutique efficace chez les patients atteints d'un lupus érythémateux disséminé (LED) et des souris modèles développant un lupus.L'autophagie est une voie intracellulaire conservée qui joue un rôle central dans le maintien de l'homéostasie cellulaire. En outre, l'autophagie a été démontrée comme un mécanisme de régulation de l'autoimmunité. Les effets bénéfiques du peptide P140 dans le lupus semblent étroitement liés à son effet d'inhibition de l’autophagie qui est hyper-activée dans le lupus. A ce jour, très peu de données sont connues concernant l'autophagie dans le SS. Le sujet de ma thèse porte i. sur l’étude et la compréhension des phénomènes de l’autophagie dans le SS et ii. sur l’effet éventuel du peptide P140 dans cette maladie.Dans cette étude, nous avons d’abord montré des effets protecteurs du P140 contre le SS dans les souris modèle MRL/lpr, comme en témoignent l’amélioration de l'inflammation, une diminution de l'infiltration lymphocytaire dans les SG de souris et une baisse des niveaux d'autoanticorps circulants. Nous avons également constaté que l'autophagie et les lysosomes étaient défectueux dans les SG des souris MRL/lpr et que le P140 rétabli le flux autophagique et l'acidité lysosomale. Ces résultats suggèrent que l'autophagie défectueuse et des défauts des lysosomes pourraient contribuer à la pathologie du SS et que les effets thérapeutiques de P140 pourraient être liés à son effet sur l'autophagie et les lysosomes.Les résultats obtenus dans le cadre de cette thèse nous offrent des informations décisives sur la pathogenèse de SS et suggèrent que l'autophagie pourrait être une cible thérapeutique de choix dans le SS. Au-delà, les effets protecteurs de P140 dans le modèle de souris SS nous éclairent sur l'application thérapeutique du P140 dans d'autres MAIs. / Sjögren's syndrome (SS) is one of the most common systemic autoimmune diseases (AIDs) in human. This disease is characterized by lymphocytic infiltration in the exocrine glands which leads to symptoms named dry eyes and dry mouth. There is no cure for SS currently. P140 peptide has been demonstrated to be an effective therapeutic tool in patients with systemic lupus erythematosus (SLE) and lupus mouse model. Autophagy is a conserved intracellular pathway that plays a central role in maintaining cellular homeostasis. In addition, autophagy has been demonstrated to be a mechanism of autoimmune regulation. The beneficial effects of P140 peptide in lupus seem to be closely related to its inhibitory effect on autophagy which is overactivated in lupus. However, the role of autophagy in SS is largely unknown. The aim of my thesis is: 1, to study the role of autophagy in SS and 2, to examine the possible effect of the P140 peptide in this disease. In this study, we first demonstrated the protective effects of P140 against SS in MRL/lpr mouse model, as evidenced by ameliorated inflammation, decreased lymphocyte infiltration in mouse salivary glands (SGs), as well as decreased levels of circulating autoantibodies. We also found that autophagy and lysosomes were defective in SGs of MRL/lpr mice and that P140 restored the autophagic flux and lysosomal acidity. These results suggest that defective autophagy and lysosome dysfunction may contribute to the pathology of SS and that the therapeutic effects of P140 may be related to its effect on autophagy and lysosomes. The results obtained in this study provide us valuable information about the pathogenesis of SS, and suggest that autophagy could be a potential therapeutic target in SS. Moreover, the protective effects of P140 in SS mouse model shed light on the therapeutic application of P140 in other AIDs.
5

Régulation des aquaporines et réponse des racines d'Arabidopsis thaliana à des stimuli abiotiques et nutritionnels. / Regulation of aquaporins and response of Arabidopsis thaliana roots to abiotic and nutritional stimuli.

Di Pietro, Magali 13 December 2011 (has links)
La conductivité hydraulique racinaire (Lpr) traduit la facilité du passage de l'eau au travers des racines. Ce paramètre, majoritairement contrôlé par l'activité de canaux hydriques membranaires (aquaporines), est modulable par diverses contraintes environnementales. Ce travail a permis de caractériser, sur un même organisme (Arabidopsis), les effets d'un ensemble de contraintes abiotiques et biotiques, représentatives de situations environnementales, sur la Lpr. Alors que la flagelline n'affecte pas la Lpr, les contraintes osmotiques (NaCl, mannitol), oxydantes (H2O2, NO) et nutritionnelles (carence en phosphate, en nitrate, culture des plantes en nuit prolongée) inhibent la Lpr. Par contre, la réalimentation en phosphate ainsi que l'addition de saccharose à des plantes cultivées en nuit prolongée stimulent la Lpr. Une approche phosphoprotéomique quantitative, basée sur l'analyse par MS de protéines microsomales racinaires purifiées à partir de plantes cultivées dans trois de ces contextes (NaCl, NO, phosphate) a permis de quantifier les variations d'abondance de l'ensemble des aquaporines racinaires ainsi que de leur état de MPT. D'un point de vue qualitatif, 22 aquaporines ont été identifiées dans la racine ainsi que plusieurs types de MPTs, incluant des nouveaux sites de phosphorylation (7), de méthylation (13 à 15), de formylation (4) et de déamidation (25 à 26). D'un point de vue quantitatif, cette étude a permis de conclure que les observations réalisées au niveau de la Lpr sont la résultante de mécanismes multifactoriels incluant l'état de phosphorylation des trois sites de l'extrémité C terminale de PIP2;1/2;2/2;3, l'état de phosphorylation de l'extrémité N terminale de PIP1;1/1;2, ainsi que les aquaporines TIPs. Ce travail permet donc de proposer de nouveaux mécanismes moléculaires impliqués dans la régulation de la Lpr en réponse à des contraintes de l'environnement / The water uptake capacity of plant roots (root hydraulic conductivity, Lpr) is mainly determined by water channels (aquaporins) and is modulated by environmental constraints. The present work characterised, in a unique organism (Arabidopsis), effects on Lpr of abiotic and biotic constraints representative of environmental situations. Whereas flagelline does not affect Lpr, osmotic (NaCl or mannitol), oxidative (H2O2 or NO) and nutritional (phosphate or nitrate starvation, prolonged night) stimuli inhibit Lpr. However, phosphate and sucrose resupply stimulate Lpr. A phosphoproteomics approach based on MS analysis of microsomal proteins extracted from roots of plants cultivated in different environmental constraints (NaCl, NO,phosphate starvation and resupply) allowed to quantify variations of abundance of roots aquaporins and of their PTMs. As a qualitative point of view, 22 aquaporins were identified in roots as well as several post-translational modifications including new sites of phosphorylation (7), methylation (13 to 15), formylation (4) and deamidation (25 to 26). From a quantitative point of view, the present work drove to the conclusion that the modulations of Lpr result from multifactorial mechanisms including the phosphorylation status of the C terminal part of PIP2;1/2;2/2;3 and of the N-terminal part of PIP1;1/1;2 and TIP aquaporins. This study proposes new molecular mechanisms implicated in Lpr regulation in response to various environmental situations.
6

Polyélectrolytes cationiques. Synthèse, caractérisation et application en analyse et élimination de l'arsenic

Sanchez Poblete, Julio 01 June 2010 (has links) (PDF)
L'arsenic, existe dans l'environnement sous une grande variété de formes et à divers degrés d'oxydation. Aux pH naturels, l'arsenic libre se rencontre essentiellement sous forme inorganique aux degrés d'oxydation +III (arsénite) et +V (arséniate). Il est reconnu que l'efficacité des processus d'élimination de l'arsenic dépend fortement de la possibilité de convertir les espèces de l'arsenic (III) en celle de l'arsenic (V), plus faciles à extraire. La recherche développée au cours de cette thèse démontre d'abord qu'il est possible d'éliminer l'arséniate de solutions aqueuses par extraction par des polymères solubles (LPR : liquid-phase polymer-based retention). La technique LPR utilise l'ultrafiltration sur membrane pour la séparation, basée sur des effets de taille, d'espèces ioniques suite à leur complexation par des polyélectrolytes solubles. Les espèces oxo-anioniques de l'arsenic(V), associés à des polyélectolytes du type polyalkyammonium, ne passent pas à travers la membrane et peuvent être ainsi séparés des espèces non-complexées de plus petite taille. Nous avons aussi montré la grande activité catalytique des matériaux composites du type nanoparticules de Pt0 et Pd0 dispersées dans des matrices de poly(pyrrole-alkylammonium), pour l'oxydation électrochimique de l'arsénite en arséniate. En particulier, des microélectrodes de carbone modifiées par des films de ces nanocomposites ont été appliquées à l'analyse de l'arsenic(III). Enfin, l'oxydation exhaustive de solutions d'arsénite a été réalisée sur des électrodes de carbone modifiées de grande surface. L'utilisation de sels poly(alkyl-ammonium) jouant le rôle à la d'électrolyte support et d'agent d'extraction des espèces de l'arsenic(V) a permis de combiner les processus d'électrocatalyse et d'extraction par LPR, permettant ainsi d'extraire efficacement des traces d'arsenic de solutions aqueuses.
7

Effect of Laser Welding and Stretch Forming on the Corrosion Performance of Hot-Dip Galvanized Steel

Su, Ken Yu Jen 17 September 2008 (has links)
The use of laser welding in the automotive industry in the past few decades has facilitated joining of hot-dip galvanized (HDG) steel sheets at high production rates and low cost. The recent development of tailor welded blanks (TWB) using laser welding allowed combinations of sheet grades and thicknesses to “tailor” the vehicle part for optimized design, structural integrity and crash performance but more importantly, reductions in weight. Welded blanks are further subjected to stamping or stretch forming prior to final assembly. Unfortunately, both welding and stretch forming cause the galvanized coating to deteriorate, and thereby, undermine the long term corrosion protection. Despite existing publications on zinc coated steel and advances in processing techniques, there is a lack of understanding on the influence of laser welding and stretch forming on the corrosion performance of HDG steel. Hence, the purpose of this study was to determine how welding speed and biaxial strain affect interstitial-free (IF) and high strength low allow (HSLA) steel coupons when they are subjected to continuous immersion and accelerated corrosion tests. The corrosion rates of the coupons were evaluated using electrochemical techniques and gravimetry. Changes in the galvanized coating were characterized using scanning electron metallography. It was observed that, the original zinc layer transformed into the delta and gamma Fe-Zn intermetallic phases locally in the heat affected zone (HAZ) after laser welding. The resulting microstructure was similar to that of a commercially galvannealed coating and exhibited superior corrosion resistance than that of pure zinc. Linear polarization resistance (LPR) measurements revealed that the zinc coating was able to protect a chemically exposed region of steel in 0.1 M NaCl solution. While the Nd:YAG laser welded coupons with narrow HAZs performed equally well as the non-welded ones, diode laser welded coupons, with a wide locally annealed coating in the HAZ, exhibited a decrease in the peak corrosion rate of zinc. Moreover, minimal amounts of rust were observed on the surface of the HAZ after testing. With biaxial strain, welded and deformed coupons generally demonstrated higher peak corrosion rates than that of undeformed welded ones. When subjected to cyclic corrosion testing according to SAE J2334, rust formed in the exposed region after one 24 hour test cycle due to wet-dry conditions. However, zinc corrosion products on the surface provided substantial corrosion resistance to the remaining zinc coating and to the steel substrate. Gravimetric measurements of welded coupons showed a linear increase in weight gain with increased exposed widths of the steel after 30 cycles but biaxial strain further increased the weight gain on deformed coupons. After 60 cycles, the trend became exponential for both welded and deformed coupons. There was a negligible difference between the corrosion performance of IF and HSLA steel. Using X-Ray diffraction and Raman spectroscopy, species of both iron and zinc corrosion products were identified. Without the application of paint coatings, zinc oxide (ZnO), zinc hydroxy chloride (ZnCl2[Zn(OH)2]4), and hydrozincite ([ZnCO3]2[Zn(OH)2]3) were responsible for passivating the surface and reducing the overall corrosion rate of the galvanized coating.
8

Effect of Laser Welding and Stretch Forming on the Corrosion Performance of Hot-Dip Galvanized Steel

Su, Ken Yu Jen 17 September 2008 (has links)
The use of laser welding in the automotive industry in the past few decades has facilitated joining of hot-dip galvanized (HDG) steel sheets at high production rates and low cost. The recent development of tailor welded blanks (TWB) using laser welding allowed combinations of sheet grades and thicknesses to “tailor” the vehicle part for optimized design, structural integrity and crash performance but more importantly, reductions in weight. Welded blanks are further subjected to stamping or stretch forming prior to final assembly. Unfortunately, both welding and stretch forming cause the galvanized coating to deteriorate, and thereby, undermine the long term corrosion protection. Despite existing publications on zinc coated steel and advances in processing techniques, there is a lack of understanding on the influence of laser welding and stretch forming on the corrosion performance of HDG steel. Hence, the purpose of this study was to determine how welding speed and biaxial strain affect interstitial-free (IF) and high strength low allow (HSLA) steel coupons when they are subjected to continuous immersion and accelerated corrosion tests. The corrosion rates of the coupons were evaluated using electrochemical techniques and gravimetry. Changes in the galvanized coating were characterized using scanning electron metallography. It was observed that, the original zinc layer transformed into the delta and gamma Fe-Zn intermetallic phases locally in the heat affected zone (HAZ) after laser welding. The resulting microstructure was similar to that of a commercially galvannealed coating and exhibited superior corrosion resistance than that of pure zinc. Linear polarization resistance (LPR) measurements revealed that the zinc coating was able to protect a chemically exposed region of steel in 0.1 M NaCl solution. While the Nd:YAG laser welded coupons with narrow HAZs performed equally well as the non-welded ones, diode laser welded coupons, with a wide locally annealed coating in the HAZ, exhibited a decrease in the peak corrosion rate of zinc. Moreover, minimal amounts of rust were observed on the surface of the HAZ after testing. With biaxial strain, welded and deformed coupons generally demonstrated higher peak corrosion rates than that of undeformed welded ones. When subjected to cyclic corrosion testing according to SAE J2334, rust formed in the exposed region after one 24 hour test cycle due to wet-dry conditions. However, zinc corrosion products on the surface provided substantial corrosion resistance to the remaining zinc coating and to the steel substrate. Gravimetric measurements of welded coupons showed a linear increase in weight gain with increased exposed widths of the steel after 30 cycles but biaxial strain further increased the weight gain on deformed coupons. After 60 cycles, the trend became exponential for both welded and deformed coupons. There was a negligible difference between the corrosion performance of IF and HSLA steel. Using X-Ray diffraction and Raman spectroscopy, species of both iron and zinc corrosion products were identified. Without the application of paint coatings, zinc oxide (ZnO), zinc hydroxy chloride (ZnCl2[Zn(OH)2]4), and hydrozincite ([ZnCO3]2[Zn(OH)2]3) were responsible for passivating the surface and reducing the overall corrosion rate of the galvanized coating.
9

Reconhecimento Automático de Placas de Automóveis Utilizando Redes de Kohonen

GONÇALVES, Pedro Rodolfo da Silva 01 September 2015 (has links)
Submitted by Fabio Sobreira Campos da Costa (fabio.sobreira@ufpe.br) on 2016-01-18T12:53:32Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Dissertação_Pedro Gonçalves.pdf: 8565820 bytes, checksum: f14c8d37ea1f5daef226a8a6f131bada (MD5) / Made available in DSpace on 2016-01-18T12:53:32Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Dissertação_Pedro Gonçalves.pdf: 8565820 bytes, checksum: f14c8d37ea1f5daef226a8a6f131bada (MD5) Previous issue date: 2015-09-01 / Punir infrações de trânsito, controlar tráfego em rodovias, controlar o acesso a áreas restritas, entre outras, são ações tomadas para melhorar o trânsito nas grandes cidades. Para realizar tais ações é necessário, portanto, identificar o veículo automotivo, utilizando, para isso, sua placa de licenciamento. Entretanto, com o aumento de automóveis nas vias urbanas, essa tarefa tornou-se muito difícil de ser realizada de uma forma eficiente por apenas agentes de trânsito, pois existe uma grande quantidade de dados a serem analisados e reportados aos órgãos competentes. Soma-se a isso, o fato de fatores emocionais, cansaços físico e mental, inerentes aos seres humanos, atrapalharem a eficácia da tarefa executada. Por isso, ferramentas que realizam o reconhecimento ótico de caracteres, Opitcal Character Recognition (OCR), vem sendo cada vez mais empregadas para realizar a identificação automática de caracteres existentes nas placas dos automóveis. Este trabalho visa descrever um sistema para identificação de veículos automotivos através de imagens estáticas, apresentando técnicas pesquisadas e estudadas em cada etapa do processo de identificação. As etapas que são apresentadas e detalhadas incluem: a identificação da placa, segmentação dos caracteres presentes na placa e o reconhecimento dos caracteres isolados. Técnicas envolvendo processamento digital de imagem como detectores de bordas, operações morfológicas, análise de componentes conectados e limiarização serão explicitadas. Redes neurais artificias são propostas para realizar o reconhecimento do caractere isolado, tais como Self-Organizing Maps (SOM) e Kernel Self-Organizing Map (KSOM), e serão pormenorizadas. Para avaliar o desempenho das técnicas empregadas nesse projeto, imagens presentes na base de dados MediaLab LPR Database foram utilizadas. Métricas como Recall, Precision e F-Score foram empregadas na avaliação de performance dos diferentes algoritmos estudados e implementados para realizar a detecção da placa, ajudando na escolha do extrator da placa do sistema final. No estágio de segmentação da placa e do reconhecimento dos caracteres isolados, a taxa de acerto foi utilizada para avaliar os algoritmos propostos. Para um grupo de 276 imagens pertencentes a uma base pública, as etapas de detecção, segmentação e reconhecimento alcançaram desempenhos semelhantes aos vigentes na literatura ANAGNOSTOPOULOS et al. (2006) e propiciaram, aproximadamente, uma taxa de acerto global do sistema OCR proposto de 85%. / Punish traffic infractions, traffic control on highways, control access to restricted areas, among others, are actions taken to improve traffic in major cities. In order to take these actions is therefore necessary to identify the motor vehicle using it licensing plate. However, with the increase of the number of cars on urban roads, this task has become very difficult to be performed effectively only by traffic agents because there is a lot of data to be analyzed and reported to the competent agencies. In addition, the fact that emotional factors, physical and mental tiredness, that inherent features to humans, hider effectiveness of task begin performed. Therefore, tools that perform optical character recognition (OCR) are begin increasingly used for automating the identification of characters on licensing plate of the vehicles. This research describes a system for identification of automotive vehicles through still images showing algorithms researched in the literature on each step of the identification process. The stages are presented and detailed include: plate identification, segmentation of the characters existing in plate and the recognition of single characters. Techniques involving digital image processing like edge detectors, morphological operations, connected component analysis and thresholding are explained. Artificial neural networks are submitted to achieve the recognition of single character, such as Self-Organizing Maps (SOM) and Kernel Self-Organizing Map (KSOM), are detailed. In order to evaluate the performance of the techniques used in this project, images from mainly the MediaLab LPR Database were used. The metrics employed to analyze the performance of algorithms implemented to detect a region of plate on image are Recall, Precision and F-Score. This metrics helped to choose the better algorithms for extraction plate on image. In the segmentation stage of the plate and the recognition of single characters, the hit rate was used to evaluate the proposed algorithms. For group of 276 images belonging a public database, the stages of detection, segmentation and recognition reached similar performance with previous approaches (ANAGNOSTOPOULOS et al., 2006), leading the proposed OCR system to 85% of hit rate.
10

Développement d'une stratégie de vaccination thérapeutique antitumorale basée sur l'utilisation de lipopolyplexes à ARN ciblant les cellules dendritiques / Preclinical Evaluation of Trimannosylated mRNA Lipopolyplexes as Therapeutic Cancer Vaccines Targeting Dendritic-Cells

Coulon Le Moignic, Aline 30 January 2017 (has links)
L'élimination des cellules tumorales par le système immunitaire repose sur la capacité des cellules dendritiques à correctement présenter l'antigène aux cellules effectrices. Nous avons donc développé une stratégie de vaccination thérapeutique basée sur des lipopolyplexes à ARNm (LPRs) : l'ARNm codant pour l'antigène est associé à un complexe de polylysine histidylée, et incorporé dans un liposome trimannosylé afin de mieux cibler les cellules dendritiques. En effet, les cellules dendritiques expriment largement les lectines de type C, qui sont des récepteurs reconnaissant principalement des résidus mannose. Dans le travail présenté ici, nous montrons que les LPR trimannosylés sont capables de fixer les cellules dendritiques humaines et murines. De manière très intéressante, nous montrons aussi que les LPR trimannosylés injectés chez la souris induisent le recrutement et l'activation de cellules dendritiques dans le ganglion drainant. De plus, quand les LPR trimannosylés vectorisent un ARNm codant pour l'antigène tumoral E7, ils sont capables d'induire une réponse T spécifique d'E7 au niveau systémique. Enfin, les LPRs trimannosylés permettent une réponse thérapeutique lorsqu'ils sont utilisés dans trois différents modèles de tumeurs : le modèle TC1 de carcinome exprimant E7, le modèle B16 de mélanome exprimant MART1 et le modèle EG7 de lymphome exprimant OVA. Cette stratégie apparaît donc prometteuse comme thérapie innovante anti-cancer. / Elimination of cancer cells requires an efficient cytotoxic immune response. In order to obtain such a response, antigens need to be uptaken by dendritic cells (DCs) and correctly presented to effector cells. We developed a strategy based on RNA lipopolyplexes (LPRs): antigenic mRNA is associated with a histidine-polylysine polyplexe and incorporated in a trimannosylated liposome to better target dendritic cells (DCs) in vivo, as DCs express several C-Type lectin receptors that preferentially bind to mannose. Here, we report that trimannosylated LPRs are efficient to target both human and murine DCs. Interestingly, in vivo experiments reveal that trimannosylated LPRs not only target DCs but also induce their recruitment and activation in draining lymph nodes. Furthermore, when combined with mRNA encoding E7 oncoprotein from HPV16, trimannnosylated LPRs trigger specific T-cell response against E7. Finally, when used as therapeutic vaccines in three different tumors models, LPRs promote curative therapeutic responses in E7-expressing TC1 tumor, in OVA-expressing EG7 lymphoma and in MART-1-expressing B16 melanoma, when combined with E7, OVA or MART-1 mRNA, respectively. Altogether, these results comfort us to considerate the use of this strategy for anti-cancer vaccine therapies.

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