<p>The development of a deuterium-deuterium/ tritium-deuterium (D-D/ D-T) pulsed neutron generator based on the principle of the Plasma Immersion Ion Implantation (PI3) technique is presented, in terms of investigating development of a compact system to generate an ultra short burst of mono-energetic neutrons (of order 1010 per second) during a short period of time (&lt / 20&mu / s) at repetition rates up to 1 kHz. The system will facilitate neutron detection techniques, such as neutron back-scattering, neutron radiography and time-of-flight activation analysis.</p> <p><br /> Aspects addressed in developing the system includes (a) characterizing the neutron spectra generated as a function of the target configuration/ design to ensure a sustained intense neutron flux for long periods of time, (b) the system was also characterised as a function of power supply operating conditions such as voltage, current, gas pressure and plasma density.</p>

Les modèles animaux d’arthrose sont utilisés sur le rat depuis des décennies pour évaluer l’efficacité analgésique de nombreux composés. Cependant, la méthodologie utilisée, en particulier les protocoles d’évaluation de la douleur, est très différente d’une étude à une autre, rendant difficile la comparaison entre chaque projet. Afin d'améliorer le transfert des résultats précliniques vers la recherche clinique, ce projet propose d'établir un protocole d'évaluation de la douleur fiable et pertinent, et de le valider à l’aide du modèle d’arthrose expérimental le plus populaire, soit l’injection intra-articulaire de mono-iodoacétate de sodium (MIA). La répétabilité et la fiabilité inter-évaluateur de diverses méthodes d’évaluation de la douleur ont été évaluées, et le protocole d'acclimatation le plus fiable a été déterminé. Ensuite, les méthodes les plus intéressantes ont été testées pour leur sensibilité à détecter les altérations douloureuses induites par l’injection de MIA, ainsi que leur réponse au traitement analgésique, soit une injection intra-articulaire de lidocaïne. Une période d'acclimatation adéquate associée à un protocole d'évaluation combinant des mesures réflexes, des comportements spontanés ainsi que des tests opérants ont témoigné avec succès des changements douloureux liés à l'injection de MIA. Le test opérant fut la méthode la plus sensible pour détecter l'effet analgésique de la lidocaïne. Cette étude a permis d’établir le protocole d’acclimatation et les méthodes de l’évaluation de la douleur les plus fiables et sensibles. Aussi, il a démontré la pertinence du test opérant pour détecter la composante affective de la douleur chez les rongeurs. / Animal models of osteoarthritis pain have been used for decades in rats to test the analgesia response of numerous compounds. Study methodology, in particular the pain assessment methods, is quite variable, making the comparison between each project difficult and sometimes simply impossible. In order to improve the translation of new therapies from the preclinical research to the clinical field, this study proposed to establish the reliability and concurrent validity of a panel of pain assessment methods. The concurrent validation was performed in the most popular osteoarthritis rat model, i.e. using the intra-articular injection of monosodium iodoacetate (MIA). The repeatability and inter-observer reliability of various pain assessment methods were evaluated, and the most reliable acclimatization protocol was determined. Then, the most reliable methods were tested comparatively in the rat MIA osteoarthritis model for their sensitivity in detecting painful changes related to the MIA injection. Their responsiveness to treatment, i.e. an intra-articular injection of lidocaine, was also assessed. A complete pain evaluation protocol and reliable acclimatization period, combining reflexive and spontaneous behavior measures as well as operant testing, successfully demonstrated the pain related changes of the MIA injection. Operant testing was the most responsive to the analgesic effect of lidocaine. This study established the most reliable and sensitive methods of pain assessment and optimized acclimatization protocol. Moreover it defined the operant testing as a highly relevant tool to demonstrate the affective component of pain in rodent.

Moléculas de L-cisteína (CSH) e L-glutationa (GSH) foram ancoradas na superfície de eletrodos de ouro, previamente modificados com uma camada autoarranjada de ácido 3-mercaptopropiônico (MPA). Esta arquitetura molecular foi importante para preservar a atividade redox dos grupos tiólicos da CSH e GSH na interface eletrodo/solução. A identificação do par redox R-S-S-R/R-SH, bem como a determinação do pKa dos grupos -SH superficiais, foram efetuadas usando voltametria cíclica em soluções de eletrólito em diferentes pH contedo ferricianeto de potássio. A presença dos grupos -SH e -S-S- na superfície dos eletrodos modificados foi ainda confirmada por Espectroscopia Raman de Superfície. Determinaram-se as constantes de velocidade de transferência de carga do processo quase reversível R-S-S-R / R-SH. Estes eletrodos modificados apresentaram resposta eletrocatalítica para a redução de espécies reativas de oxigênio (ROS), como peróxido de hidrogênio e para a oxidação de compostos com atividade antioxidante como a quercetina. Demonstrou-se que a presença de íons Cu2+ na superfície destes eletrodos é capaz de deslocar o equilíbrio do par R-SS-R/R-SH, no sentido oxidativo. Métodos de quantificação para estes compostos foram desenvolvidos por amperometria hidrodinâmica e voltametria cíclica. / L-cysteine molecules (CSH) and L-glutathione (GSH) were anchored on the surface of gold electrodes, previously modified with a self assembled monolayer of 3-mercaptopropionic acid (MPA). This molecular architecture was important to preserve the redox properties of the thiol groups of CSH and GSH in the interface electrode / solution. The identification of the redox couple RSSR / R-SH and the determination of the pKa of -SH groups surface were made using cyclic voltammetry in electrolyte solutions at different pH contents potassium ferricyanide. The presence of the -SH and -SS- modified electrode surface was further confirmed by Raman spectroscopy of surface. It was determined the rate constants of direct electron transfer of quasi-reversible coupled R-SS-R/R-SH. The modified electrodes showed electrocatalytic response to the reduction of reactive oxygen species (ROS) such as hydrogen peroxide and the oxidation of compounds with antioxidant activity such as quercetin. It was demonstrated that presence of Cu2+ ions on the electrode surface can shift the equilibrium of the RSSR/R-SH redox coupled into oxidative direction. Hydrogen peroxide and Quercetin were detected at these modified electrodes using amperometry and hydrodynamic cyclic voltammetry.

Moléculas de L-cisteína (CSH) e L-glutationa (GSH) foram ancoradas na superfície de eletrodos de ouro, previamente modificados com uma camada autoarranjada de ácido 3-mercaptopropiônico (MPA). Esta arquitetura molecular foi importante para preservar a atividade redox dos grupos tiólicos da CSH e GSH na interface eletrodo/solução. A identificação do par redox R-S-S-R/R-SH, bem como a determinação do pKa dos grupos -SH superficiais, foram efetuadas usando voltametria cíclica em soluções de eletrólito em diferentes pH contedo ferricianeto de potássio. A presença dos grupos -SH e -S-S- na superfície dos eletrodos modificados foi ainda confirmada por Espectroscopia Raman de Superfície. Determinaram-se as constantes de velocidade de transferência de carga do processo quase reversível R-S-S-R / R-SH. Estes eletrodos modificados apresentaram resposta eletrocatalítica para a redução de espécies reativas de oxigênio (ROS), como peróxido de hidrogênio e para a oxidação de compostos com atividade antioxidante como a quercetina. Demonstrou-se que a presença de íons Cu2+ na superfície destes eletrodos é capaz de deslocar o equilíbrio do par R-SS-R/R-SH, no sentido oxidativo. Métodos de quantificação para estes compostos foram desenvolvidos por amperometria hidrodinâmica e voltametria cíclica. / L-cysteine molecules (CSH) and L-glutathione (GSH) were anchored on the surface of gold electrodes, previously modified with a self assembled monolayer of 3-mercaptopropionic acid (MPA). This molecular architecture was important to preserve the redox properties of the thiol groups of CSH and GSH in the interface electrode / solution. The identification of the redox couple RSSR / R-SH and the determination of the pKa of -SH groups surface were made using cyclic voltammetry in electrolyte solutions at different pH contents potassium ferricyanide. The presence of the -SH and -SS- modified electrode surface was further confirmed by Raman spectroscopy of surface. It was determined the rate constants of direct electron transfer of quasi-reversible coupled R-SS-R/R-SH. The modified electrodes showed electrocatalytic response to the reduction of reactive oxygen species (ROS) such as hydrogen peroxide and the oxidation of compounds with antioxidant activity such as quercetin. It was demonstrated that presence of Cu2+ ions on the electrode surface can shift the equilibrium of the RSSR/R-SH redox coupled into oxidative direction. Hydrogen peroxide and Quercetin were detected at these modified electrodes using amperometry and hydrodynamic cyclic voltammetry.

L'imagerie mono-pixel est un concept récent qui permet l'obtention d'images à un coût relativement faible par une compression des données durant l'acquisition. L'architecture d'une caméra mono-pixel comprend seulement deux éléments, un modulateur spatial de la lumière et un détecteur ponctuel. L'idée est de mesurer, au niveau du détecteur, la projection de la scène observée -l'image- avec un certain motif. Le post-traitement d'une séquence de mesures obtenues avec différents motifs permet de restaurer l'image de la scène. L'imagerie mono-pixel possède plusieurs avantages qui sont d'un intérêt pour différentes applications, en particulier dans le domaine biomédical. Par exemple, une caméra mono-pixel résolue en temps bas coût est bénéfique pour l'imagerie de temps de vie de fluorescence. Un tel système peut également être couplé à un spectromètre afin de compléter le temps de vie avec une information spectrale. Cependant, la limite principale de l'imagerie mono-pixel est la vitesse d'acquisition et/ou de l'étape de restauration d'image qui est, à ce jour, non compatible avec des applications temps réel. Le but de cette thèse est de développer des méthodes rapides d'acquisition et de restauration des images à visée d'applications biomédicales. Tout d'abord, une stratégie d'acquisition basée sur les algorithmes de compression dans le domaine ondelettes est proposée. Celle-ci accélère le temps de restauration de l'image par rapport aux schémas d'acquisition classiques basés sur l'acquisition comprimée. Dans un second temps, une nouvelle méthode pour lever une contrainte expérimentale de positivité sur les motifs est détaillée. Comparée aux approches classiques, cette méthode basée sur une factorisation en matrices non-négatives permet de diviser par deux le nombre de motifs envoyés au modulateur spatial de la lumière, entrainant ainsi une division par deux du temps d'acquisition total. Enfin, l'applicabilité de ces techniques est démontrée pour de l'imagerie multispectrale et/ou résolue en temps, modalités courantes dans le domaine biomédical. / Single-pixel imaging is a recent paradigm that allows the acquisition of images at a reasonably low cost by exploiting hardware compression of the data. The architecture of a single-pixel camera consists of only two elements, a spatial light modulator and a single point detector. The key idea is to measure, at the detector, the projection (i.e., inner product) of the scene under view -the image- with some patterns. The post-processing of a measurements sequence obtained with different patterns permits to restore the desired image. Single-pixel imaging has several advantages, which are of interest for different applications, especially in the biomedical field. In particular, a time-resolved single-pixel imaging system benefits to fluorescence lifetime sensing. Such a setup can be coupled to a spectrometer to supplement lifetime with spectral information. However, the main limitation of single-pixel imaging is the speed of the acquisition and/or image restoration that is, as of today, not compatible with real-time applications. This thesis investigates fast acquisition/restoration schemes for single-pixel camera targeting biomedical applications. First, a new acquisition strategy based on wavelet compression algorithms is reported. It is shown that it can significantly accelerate image recovery compared to conventional schemes belonging to the compressive sensing framework. Second, a novel technique is proposed to alleviate an experimental positivity constraint of the modulation patterns. With respect to the classical approaches, the proposed non-negative matrix factorization based technique permits to divide by two the number of patterns sent to the spatial light modulator, hence dividing the overall acquisition time by two. Finally, the applicability of these techniques is demonstrated for multispectral and/or time-resolved imaging, which are common modalities in biomedical imaging.

Ce travail de thèse est dédié à l'étude de quelques phénomènes de surface impliquant des processus d'interactions à l'échelle nanométrique. Les expériences sont réalisées à l'aide un microscope à force atomique (AFM) à grande sensibilité, utilisant un interféromètre différentiel permettant d'atteindre une résolution de E-28m2/Hz dans la mesure de la déflexion de la sonde de force. Combiné à une approche originale d'analyse du bruit thermique, cet outil permet une caractérisation quantitative de la réponse mécanique de systèmes de taille micrométrique et nanométrique, tel que des micro-leviers ou des nanotubes de carbone, sur une large plage de fréquence.La première partie de mon travail porte sur la viscoélasticité du revêtement de leviers AFM. Mis en évidence par un bruit thermique en 1/f à basse fréquence, ce phénomène est présent lorsque le micro-levier est recouvert d'une couche nanométrique de métal (or, aluminium, platine, etc.) À l'aide du théorème fluctuation-dissipation et des relations de Kramers-Kronig, nous mesurons la dépendance en fréquence de cet amortissement viscoélastique dans une large gamme de fréquence (1Hz à 20 kHz. Nous observons une dépendance en fréquence générique sous la forme d'une loi de puissance pour ce processus de dissipation, avec un petit coefficient négatif qui dépend du matériau considéré. L'amplitude de cet effet est linéaire avec l'épaisseur du revêtement, démontrant ainsi que le mécanisme de dissipation est une propriété du volume de la couche métallique plutôt que de ses interfaces.La deuxième partie de mon travail se concentre sur de nouvelles expériences sur l'interaction de nanotubes de carbone avec des surfaces planes. En utilisant notre AFM, nous réalisons une mesure directe de la réponse mécanique (raideur, dissipation) du contact entre le nanotube et la surface, dans une géométrie de pelage (le nanotube est partiellement adsorbé sur la surface). Les résultats de ce protocole sont en accord avec la mesure de la raideur dynamique déduite de l'analyse du bruit thermique, démontrant une dépendance inattendue en loi de puissance de la raideur du contact en fonction de la fréquence. Nous proposons quelques origines physiques possibles pour expliquer ce comportement, tel qu'une couche de carbone amorphe autour du nanotube. / In this thesis, we test some interactions involving surfaces processes at the nanometer scale. The experiments are conducted with a highly sensitive interferometric Atomic Force Microscope (AFM), achieving a resolution down to E-28m2/Hz for the measurement of deflection. Combined with original thermal noise analysis, this tool allows quantitative characterization of the mechanical response of micrometer and nanometer sized systems, such as microcantilevers or carbon nanotubes, on a large frequency range.The first part of my work deals with the viscoelasticity of the coating of AFM cantilevers. Evidenced by a 1/f thermal noise at low frequency, this phenomenon is present when a cantilever is coated with a metallic layer (gold, aluminium, platinium, etc...). Using the fluctuation dissipation theorem and Kramers Kronig relations, we extract the frequency dependance of this viscoelastic damping on a wide range of frequency (1Hz to 20kHz). We find a generic power law dependence in frequency for this dissipation process, with a small negative coefficient that depends on materials. The amplitude of this phenomenon is shown to be linear in the coating thickness, demonstrating that the damping mechanism takes its roots in the bulk of the metallic layer.The second part of my work tackles new experiments on the interaction of carbon nanotubes with flat surfaces. Using our AFM, we perform a true mechanical response measurement of the rigidity and dissipation of the contact between the nanotube and the surface, in a peeling configuration (the nanotube is partially absorbed to the substrate). The results of this protocol are in line with the dynamic stiffness deduced from the thermal noise analysis, showing an unexpected power law dependence in frequency for the contact stiffness. We suggest some possible physical origins to explain this behavior, such as an amorphous carbon layer around the nanotube.

Dans ce travail, nous décrivons la méthode de synthèse, la structure, les propriétés et quelques applications en catalyse de différentes formes du carbone, en particulier les nanostructures carbonées (Chapitre I). La technique de dépôt chimique en phase vapeur en réacteur à lit fluidisé a été utilisée pour le dépôt de métaux ou d’oxydes de métaux sur des supports comme l’alumine ou la silice. Le matériau résultant est utilisé comme catalyseur pour la synthèse de diverses nanostructures carbones par dépôt chimique en phase vapeur catalytique : nanotubes de carbone mono- et multi-feuillets (SWCNTs, MWCNTs), nanofibres de carbone (CNFs), et des nanotubes de carbone (N-MWCNTs) ou nanofibres (N-CNFs) dopés en azote (Chapitre II). Après dissolution du catalyseur par un traitement a l'acide sulfurique ou par la soude, suivit dans le cas des MWCNTs et CNFs, par un traitement à l'acide nitrique pour générer des fonctions carboxyliques de surface, les nanostructures carbonées ont été utilisées comme supports de catalyseurs. L’hydrogénation du cinnamaldehyde a été choisit comme réaction modèle pour comparer les performances de différents catalyseurs bimétalliques de Pt-Ru en fonction de la nature du support. Une étude paramétrique détaillée ainsi que l'étude de l'effet d'un traitement thermique sur l'amélioration des performances du catalyseur de Pt-Ru/MWCNT sont présentes. Une explication de l'augmentation des performances catalytiques sera proposée après analyses du catalyseur par HREM, EDX, EXAFS et WAXS (Chapitre III). Les nanostructures carbonées préparées seront également testées comme supports conducteurs d'électrocatalyseurs pour l'élaboration d'électrodes de "polyelectrolyte membrane fuel cells" (PEMFC). / In this work, we describe the synthesis, structure, physical properties and some applications in catalysis of previously known carbon allotropes, and recently discovered carbon nanostructure (Chapter I). First, FB-OM-CVD deposition was used for metal or metal oxide deposition on metal oxide supports like alumina or silica, leading to the production of supported catalysts. The resulting material was used as catalyst for catalytic chemical vapor deposition of carbonaceous nanostructures i.e single- and multi-walled carbon nanotubes (SWCNTs, MWCNTs), carbon nanofibers (CNFs), and nitrogen doped carbon nanotubes (N-MWCNTs) and nanofibers (N-CNFs) (Chapter II). After catalyst removal by a H2SO4 or NaOH treatments and carboxylic surface group generation by a HNO3 treatment in the case of MWCNTs and CNFs, the carbon nanostructures were used as supports for heterogeneous catalysis. The hydrogenation of cinnamaldehyde was used as a model reaction to compare the performance of different bimetallic Pt-Ru catalysts as a function of the nature of the support. Detailed parametric studies as well as the effect of a heat treatment on the performance improvement of the Pt-Ru/MWCNT catalyst are presented. An explanation for the increase of performances upon heat treatment will be proposed after HREM, EDX, EXAFS and WAXS characterization of the catalyst (Chapter III). The prepared carbon nanostructures were also tested as supports for Pd based electrocatalysts for direct alkaline fuel cells applications in both cathodes for the ORR reaction and anodes for alcohols oxidation.

Submitted by Rosivalda Pereira (mrs.pereira@ufma.br) on 2017-05-05T19:45:04Z No. of bitstreams: 1 RicardoSousaFerreira.pdf: 2802747 bytes, checksum: 0d4bf284379fe32714f3b112e464cf64 (MD5) / Made available in DSpace on 2017-05-05T19:45:04Z (GMT). No. of bitstreams: 1 RicardoSousaFerreira.pdf: 2802747 bytes, checksum: 0d4bf284379fe32714f3b112e464cf64 (MD5) Previous issue date: 2016-03-24 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Fundação de Amparo à Pesquisa e ao Desenvolvimento Científico e Tecnológico do Maranhão (FAPEMA) / Currently, the amino acid salt crystals are extensively studied, primarily because of their possible application in opto-electronic devices. Many amino acids complexed with chlorine crystals were synthesized and characterized, and suggested as promising materials in frequency conversion. However, the characterization of L-isoleucine hydrochloride monohydrate crystals (L-Ile.H2O.HCl) is poor because to date, one article has been published and only the authors determined the crystal structure of the synthesized material. Thus, the objective of this study was to synthesize crystals of L-Ile.HCl.H2O by the method of slow evaporation and characterize them by X-Ray Fluorescence (XRF), Differential Thermal Analysis (DTA), Differential Scanning Calorimetry (DSC), Thermogravimetric Analysis (TG), X-Ray diffraction (XRD) as a function of temperature and time, Raman scattering as a function of temperature and heat treating the material in a sealed glass tube with argon atmosphere for 24h at 170 °C. The XRF confirms the presence of chlorine. The XRD at 25 oC shows that the crystal belongs to orthorhombic system with lattice parameters a = 5.873 (3) Å, b = 24.814 (4) Å, c = 6.873 (5) Å. The TG, DTA and DSC indicated that the material loses water of solvation and crystallization at approximately 55 °C and 132 °C, respectively .The DRX a function of temperature, the material shows phase transformation starts at 60 oC and 155 oC extends to. The XRD at 140 oC shows that after 32h, the crystal loses water and chlorine. Raman spectra as a function of temperature, confirm the phase transformation at 60 °C and 100 °C. The material when subjected to 170 °C, for a period of 24 sealed in a glass tube with an inert atmosphere (Ar) and undergoes vaporization sublimate the same orthorhombic phase, when it has its temperature reduced to 25 °C. Therefore, the L-Ile.HCl.H2O crystal is not a material suitable for use in optical devices due to their low thermal stability. / Atualmente, os cristais de sais de aminoácidos são amplamente estudados, principalmente devido à sua possível aplicação em dispositivos opto eletrônicos. Muitos cristais de aminoácidos complexados com cloro foram sintetizados, caracterizados e sugeridos como materiais promissores na conversão de frequência. No entanto, a caracterização de cristais de L-isoleucina hidroclorídrica monohidratada (L-Ile.H2O.HCl) é deficiente, pois até o momento, um único artigo foi publicado e os autores apenas determinaram a estrutura cristalina do material sintetizado. Dessa forma, o objetivo do presente trabalho foi sintetizar cristais de L-Ile.HCl.H2O pelo método de evaporação lenta e caracterizá-los por Fluorescência de Raios-X (FRX), Análise Térmica Diferencial (DTA), Calorimetria Exploratória Diferencial (DSC), Análise Termogravimétrica (TG), Difração de Raios-X (DRX) em função da temperatura e do tempo, espalhamento Raman em função da temperatura e tratar termicamente o material em um tubo de vidro selado com atmosfera de argônio por 24h a 170 oC. A FRX confirmou a presença de cloro. O DRX a 25 oC mostrou que o cristal pertence ao sistema ortorrômbico, com parâmetros de rede a = 5,873(3) Å, b = 24,814(4) Å, c = 6,873(5) Å. O TG, DTA e DSC indicaram que o material perde água de solvatação e cristalização em aproximadamente 55 oC e 132 oC, respectivamente. O DRX em função da temperatura, revelou que o material inicia transformação de fase em 60 oC e se estende até 155 oC. O DRX a 140 oC mostrou que após 32h, o cristal perdeu água e cloro. Os espectros Raman em função da temperatura, confirmaram as transformações de fase em 60 oC e 100 oC. O material quando submetido a 170 oC, por um período de 24h selado em um tubo de vidro com atmosfera inerte (Ar), sofreu vaporização e ressublimou na mesma fase ortorrômbica, quando teve sua temperatura reduzida a 25 oC. Portanto, o cristal de L-Ile.HCl.H2O não é um material indicado para ser utilizado em dispositivos ópticos devido a sua baixa estabilidade térmica.

Trinucleotide repeat (TNR) instability including repeat expansions and repeat deletions is the cause of more than 40 inherited incurable neurodegenerative diseases and cancer. TNR instability is associated with DNA damage and base excision repair (BER). In this dissertation research, we explored the mechanisms of BER-mediated TNR instability via biochemical analysis of the BER protein activities, DNA structures, protein-protein interaction, and protein-DNA interaction by reconstructing BER in vitro using synthesized oligonucleotide TNR substrates and purified human proteins. First, we evaluated a germline DNA polymerase β (pol β) polymorphic variant, pol βR137Q, in leading TNR instability-mediated cancers or neurodegenerative diseases. We find that the pol βR137Q has slightly weaker DNA synthesis activity compared to that of wild-type (WT) pol β. Because of the similar abilities between pol βR137Q and WT pol β in bypassing a template loop structure, both pol βR137Q and WT pol β induces similar amount of repeat deletion. We conclude that the slightly weaker DNA synthesis activity of pol βR137Q does not alter the TNR instability compared to that of WT pol β, suggesting that the pol βR137Q carriers do not have an altered risk in developing TNR instability-mediated human diseases. We then investigated the role of DNA synthesis activities of DNA polymerases in modulating TNR instability. We find that pol βY265C and pol ν with very weak DNA synthesis activities predominantly promote TNR deletions. We identify that the sequences of TNRs may also affect DNA synthesis and alter the outcomes of TNR instability. By inhibiting the DNA synthesis activity of pol β using a pol β inhibitor, we find that the outcome of TNR instability is shifted toward repeat deletions. The results provide the direct evidence that DNA synthesis activity of DNA polymerases can be utilized as a potential therapeutic target for treating TNR expansion diseases. Finally, we explored the role of post-translational modification (PTM) of proliferating cell nuclear antigen (PCNA) on TNR instability. We find that ubiquitinated PCNA (ub-PCNA) stimulates Fanconi associated nuclease 1 (FAN1) 5’-3’ exonucleolytic activities directly on hairpin structures, coordinating flap endonuclease 1 (FEN1) in removing difficult secondary structures, thereby suppressing TNR expansions. The results suggest a role of mono-ubiquitination of PCNA in maintaining TNR stability by regulating nucleases switching. Our results suggest enzymatic activities of DNA polymerases and nucleases and the regulation of the activities by PTM play important roles in BER-mediated TNR instability. This research provides the molecular basis for future development of new therapeutic strategies for prevention and treatment of TNR-mediated neurodegenerative diseases.

Pour un terminal mobile alimenté sur batterie, le rendement de l’amplificateur de puissance (AP) doit êtreoptimisé. Cette optimisation peut rendre non-linéaire la fonction d’amplification de l’AP. Pour compenser lesdistorsions introduites par le caractère non-linéaire de l’AP, un détecteur numérique fondé sur un modèle deVolterra peut être utilisé. Le comportement de l’AP et le canal étant modélisé par le modèle de Volterra, uneapproche par filtrage de Kalman (FK) permet d’estimer conjointement les noyaux de Volterra et les symbolestransmis. Dans ce travail, nous proposons de traiter cette problématique dans le cadre d’une liaison montantedans un contexte radio intelligente (RI). Dans ce cas, des contraintes supplémentaires doivent être prises encompte. En effet, étant donné que la RI peut changer de bande de fréquence de fonctionnement, les nonlinéaritésde l’AP peuvent varier en fonction du temps. Par conséquent, nous proposons de concevoir une postdistorsionnumérique fondée sur une modélisation par modèles multiples combinant plusieurs estimateurs àbase de FK. Les différents FK permettant de prendre en compte les différentes dynamiques du modèle.Ainsi, les variations temporelles des noyaux de Volterra peuvent être suivies tout en gardant des estimationsprécises lorsque ces noyaux sont statiques. Le cas d’un signal monoporteuse est adressé et validé par desrésultats de simulation. Enfin, la pertinence de l’approche proposée est confirmée par des mesures effectuéessur un AP large bande (300-3000) MHz. / For a battery driven terminal, the power amplifier (PA) efficiency must be optimized. Consequently,non-linearities may appear at the PA output in the transmission chain. To compensatethese distortions, one solution consists in using a digital post-distorter based on aVolterra model of both the PA and the channel and a Kalman filter (KF) based algorithm tojointly estimate the Volterra kernels and the transmitted symbols. Here, we suggest addressingthis issue when dealing with uplink cognitive radio (CR) system. In this case, additionalconstraints must be taken into account. Since the CR terminal may switch from one subbandto another, the PA non-linearities may vary over time. Therefore, we propose to designa digital post-distorter based on an interacting multiple model combining various KF basedestimators using different model parameter dynamics. This makes it possible to track thetime variations of the Volterra kernels while keeping accurate estimates when those parametersare static. Furthermore, the single carrier case is addressed and validated by simulationresults. In addition, the relevance of the proposed approach is confirmed by measurementscarried on a (300-3000) MHz broadband PA.