Este estudo in vitro teve como objetivo avaliar os efeitos moleculares do TGF-β1, com diferentes períodos de suplementação, sobre a formação do fenótipo osteogênico das células MC3T3-E1, comparando-os com células tratadas com AA+β-GP suplementados com Dex e/ou TGF-β1, sem e com a neutralização dos receptores de TGF-β1. A expressão gênica do próprio TGF-β1 e Smad3 foram analisadas, bem como, a diferenciação das células osteogênicas e a biomineralização. As células tratadas com TGF-β1 sem neutralização de receptores apresentam efeito inibitório nos estágios mais avançados da diferenciação dos osteoblastos e da biomineralização in vitro, mas expressarem alguns marcadores importantes envolvidos na mineralização. Observaram-se nódulos de mineral em todos os tratamentos das células que tiveram os receptores de TGF-β1 neutralizados, mas houve uma diminuição na expressão de alguns genes. Os resultados confirmam a complexidade da via de sinalização do TGF-β1, mostrando que existem lacunas para que seja entendido o mecanismo dessa molécula na biologia osteoblástica. / This in vitro study aimed to evaluate the molecular effects of TGF-β1, with different supplementation time periods on the establishment of MC3T3-E1 cells, comparing with cells treated with AA+β-GP supplemented with Dex and/or TGF-β1, without or with neutralization of TGF-β1 receptors. The gene expression of the TGF-β1 and Smad3 were analyzed, as well as the osteoblast differentiation and biomineralization. The cells treated with TGF-β1 without neutralization of receptors have had inhibitory effect on some important stages of osteoblast differentiation and biomineralization in vitro, but expressed some important mineralization markers. Mineral nodules were observed in all treatments of cells with their TGF-β1 receptors neutralized, but there was a decrease in the expression of some important genes. The results confirm the complexity of the pathway signaling of TGF-β1, showing that there are gaps for understand the mechanisms of this molecule in the biology of osteoblasts.

This diploma thesis is focused on the charge exchange processes between projectile and target studied by the Low Energy Ion Scattering (LEIS) technique. Basic premise to investigate charge exchange processes is correct cleaning processes and proper settings of experimental instrument Qtac 100 placed in the Central European Institute of Technology (CEITEC) in Brno. Ion fraction expresses neutralization rate of the projectile. The parametr is investigated for clean and oxidized polycrystalline copper. Oxygen presence performs a significant part of reionization of backscattered neutralized projectiles.

Antiviral drug resistance is a major problem in the treatment of viral infections, including influenza and hepatitis C virus (HCV). Influenza neuraminidase (NA) is a viral sialidase on the surface of the influenza virion and a primary antiviral target in influenza. Two subtypes of NA predominate in humans, N1 and N2, but different patterns of drug resistance have emerged in each subtype. To provide a framework for understanding the structural basis of subtype specific drug resistance mutations in NA, we used molecular dynamics simulations to define dynamic substrate envelopes for NA to determine how different patterns of drug resistance have emerged in N1 and N2 NA. Furthermore, we used the substrate envelope to analyze HCV NS3/4A protease inhibitors in clinical development. In addition, influenza hemagglutinin (HA) is a primary target of neutralizing antibodies against influenza. Novel broadly neutralizing antibodies (BnAbs) against the stem region of HA have been described and inhibit several influenza viral subtypes, but antibody neutralization escape mutations have emerged. We identified potential escape mutations in broadly neutralizing antibody F10 that may impact protein dynamics in HA that are critical for function. We also solved crystal structures of antibody fragments that are important for understanding the structural basis of antibody binding for influenza BnAbs. These studies can inform the design of improved therapeutic strategies against viruses by incorporating an understanding of structural elements that are critical for function, such as substrate processing and protein dynamics, into the development of novel therapeutics that are robust against resistance.

Les sédiments urbains et résidus minier sont deux sources de pollution potentielle pour l’environnement et plus particulièrement les eaux de surfaces ou les eaux souterraines. L’altération chimique de ces interfaces solides par contact avec une source d’acidité ou d’alcalinité via l’air ou l’eau, est susceptible de se traduire par une dissolution des phases minérales et organiques et d’induire une mobilisation des éléments majeurs et traces métalliques. Ces mécanismes sont encore mal décrits et modélisés pour ce type de matrices très complexes. Cette thèse étudie donc le potentiel de mobilisation des éléments majeurs et traces métalliques de diverses interfaces carbonaté ou non carbonaté (pour l’étude du drainage minier acide et neutre contaminé). En supplément, des interfaces minérales pures ont été utilisées pour simuler en laboratoire des assemblages de phases et identifier les mécanismes croisés impliqués dans le drainage minier acide et neutre contaminé. Toutes ces matrices ont été soumises à des tests de capacité de neutralisation acido-basique (mise en contact avec une source de protons ou d’alcalinité), avec le suivi du pH (pouvoir tampon), de la conductivité et de la mobilisation élémentaire (majeurs et éléments traces métalliques). Les données expérimentales ont été modélisées avec le logiciel de spéciation géochimique PHREEQC. La combinaison des volets d’expérimentation et de modélisation, qui a très rarement été développé sur des interfaces solides aussi complexes, a permis l’identification (i) des réactions de dissolution des phases constitutives des interfaces polluées avec les réactions de sorption impliquées dans la mobilisation de leurs éléments majeurs et traces métalliques, (ii) de la spéciation des éléments majeurs et traces métalliques dans ces interfaces et dans les solutions en équilibre avec les phases solides. Ce travail de thèse permet donc d’aboutir à une méthodologie robuste, précise et réplicable permettant une caractérisation fine de la spéciation en phase liquide et solide des polluants métalliques dans les interfaces contaminées. Cette méthodologie constitue une base cruciale pour comprendre et prédire l’évolution des matières solides contaminées (sédiments urbains et déchets miniers) en fonction des différents modes de gestion : dépollution, valorisation et recyclage. / Urban sediments and mine tailings constitute two potential sources of pollution for the environment, especially surface water or groundwater. The chemical alteration of these solid matrices by contact with a source of acidity or alkalinity via air or water is likely to result in the dissolution of the mineral and organic phases and to induce the mobilization of majors and trace elements. These mechanisms are still poorly described and modeled for this type of very complex matrices. This thesis investigates potential for the mobilization of major and trace metals elements of various contaminated complex matrices, including an urban infiltration basin sediment and two carbonated and non-carbonated mining waste (for the study of contaminated acid mining drainage and contaminated neutral drainage). Besides, pure minerals were used to simulate phase mixture at the laboratory and identify the crossed mechanisms involved in contaminated acid and neutral mine drainage. All these matrices were subjected to acid-base neutralization capacity tests (solids put into contact with a source of protons or alkalinity), with monitoring of the pH (buffer capacity), the conductivity and the elemental release (major and trace metal elements). Experimental data were modeled with the PHREEQC geochemical speciation software. The combination of experimental and modeling approaches, which had very rarely been developed on such complex solid matrices, allowed the identification of (i) the dissolution reactions of the constitutive phases of the polluted matrices with the sorption reactions involved in the mobilization of their major and trace metal elements, (ii) the speciation of the major and trace metal elements in these matrices and in solution in equilibrium with the solid phases. This thesis, therefore, leads to a robust, precise and replicable methodology allowing a fine characterization of liquid and solid phase speciation of metallic pollutants in contaminated matrices. This methodology constitutes a crucial basis for understanding and predicting the evolution of contaminated solids (urban sediments and mining waste) according to different management methods: decontamination, recovery, and recycling.

No description available.

Multiple-Input-Multiple-Output (MIMO) antenna technology refers to an antenna with multiple radiators at both transmitter and receiver ends. It is designed to increase the data rate in wireless communication systems by achieving multiple channels occupying the same bandwidth in a multipath environment. The main drawback associated with this technology is the coupling between the radiating elements. A MIMO antenna system merely acts as an antenna array if the coupling between the radiating elements is high. For this reason, strong decoupling between the radiating elements should be achieved, in order to utilize the benefits of MIMO technology. The main objectives of this thesis are to investigate and implement several printed MIMO antenna geometries with integrated decoupling approaches for WLAN, WiMAX, and 5G applications. The characteristics of MIMO antenna performance have been reported in terms of scattering parameters, envelope correlation coefficient (ECC), total active reflection coefficient (TARC), channel capacity loss (CCL), diversity gain (DG), antenna efficiency, antenna peak gain and antenna radiation patterns. Three new 2×2 MIMO array antennas are proposed, covering dual and multiple spectrum bandwidths for WLAN (2.4/5.2/5.8 GHz) and WiMAX (3.5 GHz) applications. These designs employ a combination of DGS and neutralization line methods to reduce the coupling caused by the surface current in the ground plane and between the radiating antenna elements. The minimum achieved isolation between the MIMO antennas is found to be better than 15 dB and in some bands exceeds 30 dB. The matching impedance is improved and the correlation coefficient values achieved for all three antennas are very low. In addition, the diversity gains over all spectrum bands are very close to the ideal value (DG = 10 dB). The forth proposed MIMO antenna is a compact dual-band MIMO antenna operating at WLAN bands (2.4/5.2/5.8 GHz). The antenna structure consists of two concentric double square rings radiating elements printed symmetrically. A new method is applied which combines the defected ground structure (DGS) decoupling method with five parasitic elements to reduce the coupling between the radiating antennas in the two required bands. A metamaterial-based isolation enhancement structure is investigated in the fifth proposed MIMO antenna design. This MIMO antenna consists of two dual-band arc-shaped radiating elements working in WLAN and Sub-6 GHz 5th generation (5G) bands. The antenna placement and orientation decoupling method is applied to improve the isolation in the second band while four split-ring resonators (SRRs) are added between the radiating elements to enhance the isolation in the first band. All the designs presented in this thesis have been fabricated and measured, with the simulated and measured results agreeing well in most cases. / Higher Committee for Education Development in Iraq (HCED)

Contexte : Le commerce illégal d’espèces sauvages implique d’importants enjeux sociétaux, mais à ce jour peu d’études s’intéressent au commerce illégal de succulentes qui sont des plantes connues pour transformer l’eau en suc leur permettant ainsi de survivre dans des régions arides (ex. cactus, aloès, etc.). S’intéresser à ce commerce est d’autant plus crucial que la passion des consommateurs pour les succulentes ne cesse de croître, poussant alors certains à adopter des comportements illégaux. Le manque de contrôle de la part des autorités compétentes et l’adoption de ces comportements illégaux favorisent le développement d’un commerce illégal de succulentes. De plus, ce commerce s’est numérisé, posant donc de nouveaux enjeux liés à l’utilisation des nouvelles technologies. Ainsi, le mémoire vise à comprendre le choix des consommateurs à importer illégalement des succulentes à l’aide de plateformes numériques. Méthodologie : Les données analysées sont issues de 14 entrevues semi-dirigées menées auprès de consommateurs ayant importé au moins une fois illégalement une succulente à l’aide d’une plateforme de commerce en ligne. Durant les entrevues, plusieurs thèmes ont été abordés tels que le contexte d’achat, les connaissances des participants concernant les lois et enjeux environnementaux et leur perception vis-à-vis de leur comportement. Résultats : Les consommateurs sont initialement motivés à importer illégalement des succulentes au nom de leur passion et/ou pour des raisons économiques. Le marché illégal de succulentes en ligne représente alors une véritable opportunité pour eux de le faire, puisqu’ils considèrent que les succulentes y sont facilement accessibles, diversifiées et à des prix concurrentiels. Parallèlement, les risques de se faire appréhender par les autorités ou de se faire frauder sont perçus comme faibles. En revanche, ces derniers naviguent dans une zone grise alimentée par leur manque de connaissances concernant le processus légal ainsi que par l’asymétrie d’information du marché. Cette dernière les empêche alors de bien évaluer la source du produit et les risques associés. Face à cette incertitude, les consommateurs recourent à plusieurs justifications permettant de se persuader, mais également de convaincre autrui que leurs comportements sont acceptables. Implications : Ce mémoire fournit une meilleure compréhension du comportement illégal des consommateurs de succulentes, puisqu’il apporte à la fois des explications théoriques et empiriques afin de comprendre ce phénomène. Finalement, cette étude offre des pistes d’interventions intéressantes à l’élaboration de campagnes d’éducation et de sensibilisation visant la réduction de cette demande qui suscite d’important risques environnementaux. / Context: The Illegal wildlife trade (IWT) raises important environmental issues. However, up to now, few studies have focused on the illegal trade in succulents. Succulents correspond to a type of plant which are known for transforming water into juice, enabling them to survive in arid or semi-arid regions. Furthermore, consumers' passion for these plants is growing all the time. But this passion leads some individuals to engage in illegal behaviour. The lack of control by the competent authorities and the adoption of these illegal behaviours encourage the development of an illegal trade in succulents. What's more, this trade has gone online, raising new issues linked to the use of new technologies. This master’s thesis aims to understand consumers' choice to import succulents illegally using digital platforms. Methods: The data analyzed come from 14 semi-structured interviews conducted with succulent consumers who had illegally imported a succulent at least once using an online trading platform. During the interviews, several themes were addressed, such as the purchasing context, participants' knowledge of trade laws and environmental issues, and their perception of their behavior. Results: Consumers are initially motivated to illegally import succulents in the name of their passion and/or for economic reasons. The illegal online succulent market then represents a real opportunity for them to do it. Indeed, they consider succulents to be easily accessible, diversified and competitively priced. At the same time, the risk of being caught by the authorities or defrauded is perceived as low. However, consumers navigate in a grey zone fuelled by their lack of knowledge of the legal process and the asymmetry of market information. The latter prevents them from properly assessing the source of the product and the associated risks. Faced with this uncertainty, consumers use several justifications to persuade themselves and others that their behaviors are acceptable. Implications: This master’s thesis provides a better understanding of the illegal behaviour of passionate succulent consumers, since it offers both theoretical and empirical explanations for this phenomenon. Finally, this research offers interesting avenues of intervention for the development of education and awareness campaigns aimed at reducing this demand, which gives rise to significant environmental risks.

Malgré l’existence d’un vaccin préventif efficace, l’infection chronique par le virus de l’hépatite B (HBV) demeure un problème majeur de santé publique. La persistance de l’infection par HBV étant clairement associée à des réponses immunitaires insuffisantes, l’immunothérapie par le vaccin à base d’ADN nu, visant à stimuler les réponses humorales et cellulaires, apparaît comme particulièrement pertinente pour la thérapie des hépatites B chroniques. Toutefois, l’efficacité thérapeutique d’une telle stratégie reste limitée chez l’homme, d’où la nécessité d’optimiser cette approche vaccinale pour une utilisation ultérieure en clinique. Ainsi, l’objectif général de ce travail de thèse était d’explorer, avec le modèle du DHBV (« Duck Hepatitis B Virus »), étroitement apparenté au HBV humain, si l’administration du vaccin à ADN par électroporation (EP) pouvait davantage améliorer son efficacité prophylactique et thérapeutique. Nous avons montré, dans un 1er temps chez des canards naïfs, que l’administration du vaccin à ADN par EP permet de potentialiser le pouvoir neutralisant et d’élargir le répertoire épitopique de la réponse humorale dirigée contre la protéine d’enveloppe du DHBV, même avec des doses d’ADN relativement faibles. Dans un 2ème temps, nous avons montré chez des animaux chroniquement infectés par le DHBV, que l’administration par EP du vaccin à ADN ciblant les protéines structurales du DHBV et le DuIFN-γ améliore considérablement l’efficacité thérapeutique du vaccin, notamment au regard de la séroconversion et de la clairance virale. Les résultats ainsi obtenus confirment l’intérêt majeur de cette approche vaccinale pour la thérapie des hépatites B chroniques / Despite the existence of an effective prophylactic vaccine, chronic hepatitis B virus (HBV) infection remains a major public health problem. Since persistence of HBV infection is mostly associated with insufficient immune responses, therefore DNA vaccination capable of activating both humoral and cellular immune responses appears as a pertinent strategy for chronic hepatitis B therapy. However, the efficacy of such therapeutic approach remains limited in humans. Improvement of DNA vaccine efficacy is therefore needed for future therapeutic applications in clinic. The main objective of this thesis was to investigate in the duck hepatitis B virus (DHBV) model, whether the protective and therapeutic efficacy of DNA vaccine can be enhanced using EP-based delivery system. Firstly, we showed in naïve ducks that EP-based delivery was able to improve the dose efficiency of DNA vaccine and to maintain a highly neutralizing, multi-specific B-cell response even with relatively low DNA doses, suggesting that it may be an effective approach for chronic hepatitis B therapy at clinically feasible DNA dose. Secondly, we showed in chronic DHBV-carriers that in vivo EP is able to dramatically enhance the therapeutic potency of DNA vaccine targeting hepadnaviral proteins. Indeed, this approach was able to consistently restore humoral immune response and to sustainably decrease and even clear viral infection. Thus, these data strongly support the use of this approach for chronic hepatitis B therapy in humans

In heterogeneous dense networks where spectrum is shared, users privacy remains one of the major challenges. When the receivers are not only interested in their own signals but also in eavesdropping other users' signals, the cross talk becomes information leakage.We propose a novel and efficient secrecy rate enhancing relay strategy EFFIN for information leakage neutralization. The relay matrix is chosen such that the effective leakage channel (spectral and spatial) is zero. Thus, it ensures secrecy regardless of receive processing employed at eavesdroppers and does not rely on wiretaps codes to ensure secrecy, unlike other physical layer security techniques such as artificial noise. EFFIN achieves a higher sum secrecy rate over several state-of-the-art baseline methods.

In heterogeneous dense networks where spectrum is shared, users' privacy remains one of the major challenges. On a multi-antenna relay-assisted multi-carrier interference channel, each user shares the spectral and spatial resources with all other users. When the receivers are not only interested in their own signals but also in eavesdropping other users' signals, the cross talk on the spectral and spatial channels becomes information leakage. In this paper, we propose a novel secrecy rate enhancing relay strategy that utilizes both spectral and spatial resources, termed as information leakage neutralization. To this end, the relay matrix is chosen such that the effective channel from the transmitter to the colluding eavesdropper is equal to the negative of the effective channel over the relay to the colluding eavesdropper and thus the information leakage to zero. Interestingly, the optimal relay matrix in general is not block-diagonal which encourages users' encoding over the frequency channels. We proposed two information leakage neutralization strategies, namely efficient information leakage neutralization (EFFIN) and local-optimized information leakage neutralization (LOPTIN). EFFIN provides a simple and efficient design of relay processing matrix and precoding matrices at the transmitters in the scenario of limited power and computational resources. LOPTIN, despite its higher complexity, provides a better sum secrecy rate performance by optimizing the relay processing matrix and the precoding matrices jointly. The proposed methods are shown to improve the sum secrecy rates over several state-of-the-art baseline methods.