The goal of this study was to characterize the binding sites on the surface of wheat roots, Triticum turgidum, involved in the adsorption of protons and metals, and quantify the thermodynamic constants needed for a surface complexation model to predict metal binding. The adsorption of protons, Cd(II), Cu(II), and Ni(II) to the root surface as a function of pH and ionic strength in single metal exposure scenarios was quantitatively described using potentiometric titrations, batch metal adsorption experiments, and the least squares fitting program FITEQL. Model predictions from single metal exposures were compared to measured metal adsorption concentrations when roots were exposed to binary and ternary combinations of the metals. Proton dissociation was a function of three discrete monoprotic acid sites on the root surface with log proton dissociation constants of -4.50, -6.23, and -7.37 respectively, upon which varied ionic strength had no effect. The total proton binding capacities for the three sites were 2.58 x 10-4, 1.29 x 10-4, and 2.58 x 10-4 M, respectively. Metal complexation was best described by a two-site model having conditional stability constant log values of 3.04 and 3.30 for Cd(II), 3.21 and 3.25 for Cu(II), and 2.83 and 2.84 for Ni(II) at ionic strength 0.01M. At ionic strength 0.1 M the conditional stability constants log values were 2.37 and 3.36 for Cd(II), 3.11 and 2.56 for Cu(II), and 2.18 and 3.00 for Ni(II). When roots were exposed to binary or ternary mixtures of the metals, the two monoprotic acid single metal model did not provide ideal fits to the data indicating that adsorption in a metal mixture scenario cannot be considered additive and is dependent on the combination of metals present in the exposure environment. The experimentally determined proton dissociation constants and metal stability constants could be used in commercial geochemical speciation programs such as Visual MINTEQ to predict metal adsorption to plants. / Natural Sciences and Engineering Research Council of Canada, The Mining Association of Canada, Ontario Power Generation, Environment Canada.

Le Coated Conductor est un empilement de couches tampon sur un substrat, il est composé d'un substrat métallique, de couches tampon, d'une couche d'YBCO et d'une couche protectrice. Développer de bons substrats métalliques, simplifier l'architecture des couches tampon et trouver des méthodes de fabrication d'YBCO économiques sont les sujets essentiels de ce domaine. On a développé un nouveau substrat bimétallique Cu-Ni par dépôt électrochimique d'une couche de Ni sur un ruban de cuivre texturé et on discute comment déposer un film de La2Zr2O7 (LZO), de même texture, sur un substrat métallique par un processus chimique en solution (CSD). La fabrication de rubans de Cu texturé par un procédé de laminage-recristallisation est présentée en premier, puis on s'intéresse au dépôt électrochimique du Ni sur ces rubans. La stabilité thermique de la texture et les propriétés magnétiques de ces substrats Cu-Ni est discutée. Le dépôt d'une couche tampon de LZO texturée sur ces substrats par le procédé CSD confirme leur intérêt potentiel pour les Coated Conductors. Le dépôt de couches de LZO sur divers substrats métalliques, la préparation de précurseurs et des substrats, la croissance épitaxiale de couches tampon de LZO sont discutés en détail. On montre que l'acetylacétonate dissout dans l'acide propionique est une bonne solution. Une couche de S de structure c(2x2) à la surface du substrat permet le contrôle de l'orientation initiale des couches de LZO. Le carbone résiduel issu de la synthèse de LZO est un facteur inhibant la croissance des grains de LZO mais son gradient sous la surface est utile. La maitrise de l'ensemble de ces facteurs permet la formation de couches de haute qualité.

Treatment of the diethyl ester of o-phenylenebis(oxamic acid) (opbaH2Et2, 1) with 5/6 equivalent of MeNH2 in abs. EtOH results in the exclusive formation of the ethyl ester of o-phenylene(N′-methyl oxamide)(oxamic acid) (opooH3EtMe, 2) in ca. 50% yield. Treatment of 2 with four equivalents of [Me4N]OH followed by the addition of Cu(ClO4)2·6H2O gave [Me4N]2[Cu(opooMe)]·H2O (3A) in ca. 80% yield. As 3A appears to be a hygroscopic solid, the related [nBu4N]+ salts [nBu4N]2[M(opooMe)]·H2O (M = Cu (3B), Ni (4)) have been synthesized. By addition of two equivalents of [Cu(pmdta)(NO3)2] to a MeCN solution of 3B the novel asymmetric trinuclear complex [Cu3(opooMe)(pmdta)2](NO3)2 (5) could be obtained in ca. 90% yield. Compounds 2, 3A, 3B, 4 and 5 have been characterized by elemental analysis and NMR/IR spectroscopy. Furthermore, the solid state structures of 3A in the form of [Me4N]2[Cu(opooMe)]·MeOH (3A′), 3B in the form of [nBu4N]2[Cu(opooMe)] (3B′), 4 in the form of [nBu4N]2[Ni(opooMe)]·1.25H2O (4′) and 5 in the form of [Cu3(opooMe)(pmdta)2] (NO3)2·3MeCN (5′), respectively, have been determined by single-crystal X-ray diffraction studies. By controlled cocrystallization, diamagnetically diluted 3B (1%) in the host lattice of 4 (99%) in the form of single crystals have been made available, allowing single crystal EPR studies to extract all components of the g-factor and the tensors of onsite CuA and transferred NA hyperfine interaction. Out of these studies the spin density distribution of the [Cu(opooMe)]2− complex fragment could be determined. The magnetic properties of 5 were studied by susceptibility measurements versus temperature. An intramolecular J parameter of −65 cm−1 has been obtained, unexpectedly, as 5 should possess two different J values due to its two different spacers between the adjacent CuII ions, namely an oxamate (C2NO3) and an oxamidate (C2N2O2) fragment. This unexpected result is explained by a summarizing discussion of the experimentally obtained EPR results (spin density distribution) of 3B, the geometries of the terminal [Cu(pmdta)]2+ fragments of 5 determined by X-ray crystallographic studies and accompanying quantum chemical calculations of the spin density distribution of the mononuclear [Cu(opooMe)]2− and of the magnetic exchange interactions of trinuclear [Cu3(opooMe)(pmdta)2]2+ complex fragments. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

There exist large number of techniques for the preparation of nanostructured materials. Among them the preparation of nanopowders by gas/vapour condensation is a popular one. Because of very high level of surface to volume ratio, powders of metals which may or may not be reactive in the bulk form undergo vigorous oxidation. Oxidation once initiated continues in an auto catalytic fashion leading to a rise in temperature further increasing the oxidation rate. Therefore, the nanopowders are consolidated in situ under high vacuum. Alternatively a thin passivating oxide layer of few nm can be produced by slow exposure to air. Such powders lend themselves to be handled in further processing in ambient atmosphere. The main objective of the present research is to understand the various scientific and technological issues involved in preparing such passivated nanopowders by levitational gas condensation (LGC) technique, a relatively less explored vapour condensation process and their subsequent consolidation by the powder metallurgical route of compaction and sintering. The nanopowders systems studied are Fe and Fe-Cu (4 wt. %Cu). In chapter 1 a brief review of the gas condensation process and the consolidation behavior of nanopowders produced by this method were carried out. Existing knowledge on various topics relevant for the present study like formation of nanoparticles, agglomeration during gas condensation, physical, structural and chemical nature of the passive layer formed during passivation, compaction and sintering behaviour of this passivated nanopowders were discussed. Chapter 2 details the synthesis of Fe nanopowders by levitational gas condensation process and its physical and structural characteristics. The nanopowders in the as synthesized condition showed extremely low packing density due to loosely packed weakly interlocked agglomerates. The nanoparticles manifest as three dimensional reticulated spongy structure composed of chains of these nanoparticles. Heat transfer calculation carried out to determine the particle temperature at different distance from the levitating drop indicates that the nanoparticles can be ferromagnetic at a distance of less than 2 mm away from the levitation drop and hence the magnetic nature of the materials plays an important role in the formation of nanoparticle chains and spongy agglomerates. Passivation of the nanopowders by slow exposure to air produces 3-4 nm thick oxide layer (Fe3O4) over α-Fe and the volume of these oxides was around 45%. The 3rd chapter presents and discusses the results of Fe-Cu alloy nanopowder synthesized by levitating gas condensation process. While synthesis of elemental nanopowders by gas condensation is straight forward as the operating conditions only influence the particle size, alloys require careful control of the levitating drop composition. Although initially we start the process with levitated drop of required composition, the vapour generated will be richer in more volatile element (Cu in our case). Thus the composition of the levitated drop progressively becomes deficient in Cu which in turn reduces Cu in the vapour. Composition of the drop can be stabilised by continuous feeding of the alloy of required composition that can be estimated from the knowledge of equilibrium relation. To establish the equilibrium relationship between composition of the liquid and vapour in evaporation and condensation, phase diagram in the liquid and vapour region was calculated and was validated by determining composition of the drops. Good agreement between the drop composition and the composition predicted by the phase diagram were observed. Various physical, chemical and structural properties of the Fe-Cu nanopowders are characterized in detail using scanning electron microscopy, transmission electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy (XPS) and thermogravimetry (TG) analysis. The overall chemical composition of the Fe-Cu alloy nanopowders and of the individual agglomerates is same as the composition of feed materials used. However, Cu was found to segregate to the surface of the nanopowders which is attributed to minimization of surface energy with Cu at the surface. The total weight loss observed in TG in flowing hydrogen indicates that the surface passive layer of Fe-Cu appears to be very thin compared to Fe. The consolidation behaviour of both Fe and Fe-Cu nanopowders was studied by both conventional and spark plasma sintering (SPS) and are discussed in chapter 4. The as collected nanopowders from the apparatus have extremely low apparent density. The powders were further subjected to soft milling in a ball mill under ethanol to disentangle the agglomerates there by improving the pack density. A tenfold improvement was achieved thus making it suitable for consolidation. Uniaxial compaction of these powders for conventional sintering at pressure below 200 MPa yielded compacts free from defects. However, at higher pressure the compacts cracks and delaminates during ejection stage. Analysis of the compaction curves helped us to understand various processes involved during compaction as well as providing explanation for lower green density of Fe-Cu powder compared to Fe. Conventional sintering of the nanopowders compacts were carried out in the flowing hydrogen atmosphere in a laboratory vacuum furnace over wide range of temperatures. Instrumented sintering experiments were also carried out in a dilatometer under hydrogen atmosphere to evaluate shrinkage rate at different temperatures. SPS were carried out under 10 Pa vacuum at a compaction pressure of 250 MPa in WC-Co die cavity. The stability, density and residual oxygen content of the sintered compacts were quantified. Detailed microstuctural analysis of the sintered samples were also carried out using optical microscopy, atomic force microscopy, scanning electron microscopy, transmission electron microscopy, scanning transmission electron microscopy and quantitative composition analysis by EDS. Conventionally sintered compacts of both the powders showed stability only when sintered at 700°C and beyond. The maximum shrinkage/densification occured around 450°C for both the powders and the densification rate observed in Fe-Cu is three times higher than Fe. This enhanced densification in Fe-Cu is attributed to an enhanced diffusivity of Fe atoms in the transient liquid Cu layer formed at the interfaces. The microstructure of Fe-Cu is completely free from any separate oxide phase unlike in samples of Fe sintered at 700°C that contain ultrafine oxide grains. This was explained on the basis of role played by acrawax, a lubricant, admixed to increase the green density. Based on the sintered densities of both SPS and conventional sintered compacts, residual oxide content of the compacts sintered at different temperature and experimentally observed shrinkage rate a phenomenological model has been proposed for the possible sequence of processes occurring during sintering of these nanopowders. The major findings of this work are summarized in chapter 6 and chapter 7 details the scope for the future work.

.L’objectif de cette étude était, en premier lieu, de mettre en place en Thaïlande un testd’adhésion par traction-écaillage sur une machine de traction classique (test« macroscopique »), de le comparer au test « microscopique » Grenoblois fonctionnant dansla chambre du MEB et de l’utiliser pour évaluer l’adhérence des calamines de process sur desaciers industriels. Deux paramètres ont été étudiés, la vitesse de déformation et la teneur desaciers en silicium. Il apparaît que l’écaillage des calamines au cours du test augmente quandaugmente la vitesse de déformation. Une vitesse de déformation élevée entraîne unedéformation au premier écaillage plus faible, donc une adhérence mesurée plus faible. Ceteffet est lié aux phénomènes de relaxation. On a pu alors montrer que la présence d’oxyde(s)contenant Si, situé(s) à l’interface avec le métal, augmentait l’adhérence. Les étudesd’oxydation dans la vapeur d’eau qui ont aussi été réalisées ont révélé que la présence desilicium réduisait la vitesse d’oxydation. En augmentant la teneur en Si, les couches defayalite et de wüstite s’épaississent ; par contre, les couches externes s’amincissent. Pour lesaciers contenant du cuivre, la vitesse d’oxydation est réduite quand la teneur en Cu estaugmentée. De la même façon, les couches internes sont plus épaisses et on observe uneaugmentation du nombre de précipités de Cu quand la teneur en cet élément augmente. / The purpose of this study was first to develop in Thailand a “macroscopic” adhesion testusing a conventional tensile machine, to compare it to the micro-tensile test used in Grenobleand sitting in the SEM chamber, and to use it for measuring adhesion of scales grown duringprocessing on industrial steels. Parameters affecting the test, i.e. strain rate and Si content ofsteels were investigated. The results showed that spallation of scales during strainingincreased with increasing tensile strain rate. A higher strain rate resulted in lower straininitiating the first spallation and lower mechanical adhesion of scales, which could beexplained by a relaxation effect. Oxide containing Si existed at the steel-scale interface andpromoted adhesion of scales. Oxidation studies were also performed, and the behaviour inwater vapour of steels with different contents of Si and Cu was investigated. Increasing Sicontent tended to decrease oxidation rate. It also resulted in the thickening of the wüstite andfayalite layers which formed by internal oxidation. When Si in steel increased, theintermediate (FeO + Fe3O4) and outermost (Fe2O3 sitting on Fe3O4) layers formed by externaloxidation were thinner. For Cu containing steel, increasing Cu content tended to decrease theoxidation rate. It also decreased the innermost and intermediate layers and resulted in moreCu precipitates along steel-scale interface.

De acordo com a Organização Mundial de Saúde (World Health Organization - WHO), aproximadamente 40 milhões de pessoas ao redor do mundo estão infectadas com HIV/AIDS. Atualmente, a epidemia tem sido controlada em grande parte do mundo ocidental, porém, projeções sugerem que, até o fim desta década, o número de incidência da doença poderá duplicar. Apesar das significantes melhoras na morbidade e mortalidade de pacientes infectados pelo HIV, o rápido surgimento de cepas resistentes aos agentes anti-HIV, além dos efeitos adversos e o alto custo de fármacos de última geração, torna-se necessário o continuo desenvolvimento de novas classes de agentes anti-HIV. A transcrição e multiplicação do RNA viral são dependentes das interações seqüência-específica entre duas proteínas reguladoras virais essenciais, Tat e Rev, com seus respectivos sítios no RNA, TAR e RRE. Durante a última década, os aminoglicosídeos foram introduzidos como ligantes universais do RNA, sendo capazes de se ligar ao TAR e ao RRE. A literatura apresenta diversos aminoglicosídeos que são capazes de se ligar ao TAR e inibir a interação Tat-TAR bem como, inibir competitivamente a ligação da proteína Rev ao RRE, como, por exemplo, a neomicina e tobramicina. Considerando a importância dos aminoglicosídeos e análogos nucleosídicos, conhecidamente eficazes na terapia antirretroviral, o trabalho foi direcionado para a síntese de conjugados de aminociclitol, 2- desoxi-estreptramina, e adenosina, bem como, dímeros de adenosina via estratégia de click chemistry por reação de cicloadição azido-alcino catalisada por Cu(I) (CuAAC). Para a síntese destes produtos, o precursor adenosina foi convertido no derivado 5\'-azido-5\'- desoxi-adenosina, o qual foi condensado com diversos diinos terminais comerciais, contendo diferentes grupos espaçantes, com a finalidade de explorar suas influências nas propriedades eletrônicas e estéricas nos conjugados de interesse frente à atividade anti-HIV. Os derivados alcinos presentes na posição C-5\' de adenosina, via grupo triazol, foram empregados para a síntese dos monômeros nucleosídeo-aminociclitóis, assim como, na síntese de dímeros nucleosíde0-aminociclitóis, via reação de cicloadição 1,3-dipolar, na presença de CuSO4, quantidade catalítica, e ascorbato de sódio, para geração in situ de Cu(I). Adicionalmente, alguns dos compostos, na concentração de 1mM, foram testados empregando o ensaio de ELISA para detecção da presença de proteína viral p24 em linhagem células H9 e avaliação de sua atividade antirretroviral. De acordo com o ensaio biológico, um dos compostos preparados apresentou, proporcionalmente ao crescimento da linhagem H9 (HIV) controle, atividade de inibição de formação da proteína viral p24 similar ao composto padrão zidovudina (AZT). Além disso, outros dois compostos também apresentaram um resultado relevante uma vez que suas atividades foram similares ao composto padrão lamivudina (3TC). Estes resultados sugerem que a presença de uma cadeia metilênica mais extensa, como cadeia lateral ou grupo espaçante, pode influenciar positivamente a atividade biológica por efeito hidrofóbico ou estérico. Por fim, os ensaios de viabilidade celular demonstraram que os compostos testados não foram citotóxicos nas condições testadas. / According to World Health Organization - WHO about 40 million of people are infected with HIV/AIDS. Currently, the epidemic has been controlled largely in the western world, since, projections suggest that, until this decade end, the disease incidence could increase. Despite significant improvements in morbidity and mortality of HIV-patients, quick emergence of resistant strains to anti-HIV agents, in addition to adverse effects and high cost of recent drugs, becomes necessary the ongoing development of new classes of HIV agents. Transcription and translation of the viral RNA are dependent of sequence-specific interactions among two essential viral regulatory proteins, Tat and Rev, and their corresponding TAR and RRE sites in HIV-1 RNA. Over the past decade, aminoglycosides were established as universal RNA linkers, being able to link to TAR and RRE. The literature reports several aminoglycosides that bind to TAR and inhibit Tat-TAR interaction, as well as, competitively inhibit the bind between Rev protein and RRE, such as: neomycin and tobramycin. Considering the importance of nucleosides analogs, effective in antiretroviral therapy, and aminoglycosides, the work was driven to the synthesis of aminocyclitol, 2- deoxy-streptamine, conjugated to the adenosine, as well as, conjugated dimers of adenosine by molecular duplication via click chemistry strategy involving copper-catalysed azide-alkyne cycloaddition reaction (CuAAC). For the synthesis of these products, the starting material adenosine was converted to 5\'-azide-5\'-deoxy-adenosine, which was conjugated with several commercials terminal dialkynes containing different intercalating groups in order to explore the influences of the steric and electronic properties of conjugates towards anti-HIV activity. Alkynes derivated at C-5\' position of adenosine, via triazole group, were used in the synthesis of nucleoside-linked aminocyclitols, as well as, nucleoside conjugated dimers by 1,3-dipolar cycloaddition reaction under microwave-assisted conditions (MW), using the catalytic system CuSO4/sodium ascorbate for the in situ generation of Cu(I). Additionally, several compounds, at concentration of 1mM, were tested in vitro by ELISA for detection of p24 protein in H9 cells to antiretroviral evaluation. According with the biologic assay, one of the compounds showed inhibition of p24 protein production similar to zidovudine (AZT), when compared to H9 cells line growth control, Furthermore, two compounds also showed important activities similar to lamivudine (3TC). These results suggest that the presence of a longer methylenic chain, as side chain or intercalating groups, could influence positively in the biologic activity due to hydrophobic or steric effects. Ultimately, the cell viability assays showed that compounds were not cytotoxic in the tested conditions.

The Korean church, famous for her rapid growth, has begun to notice a downward trend in her growth rate since the mid-eighties. Although many reputable investigations have recently been carried out with regard to this downward slide, these investigations have overlooked the full meaning of preaching in the interaction between church and culture. In view of this, this study sets the following four aims: (1) to investigate the reasons behind church decline in terms of preaching in the interaction between church and culture in Korea; (2) to interpret preaching in the interaction between church and culture biblically, historically and theologically in order to understand the normative Christian perceptions and practices of preaching; (3) to attempt an integration between the descriptive and the normative; and (4) to propose developmental strategies for the Korean church. To achieve these purposes, two kinds of methods are employed in this study: (a) an analysis of preaching in the interaction between church and culture both in Korea and in the normative Christian sources, with the model advocated by D Browning (1991); and (b) qualitative interviewing as an empirical interpretation with a model based on the findings of Rubin&Rubin (1995). Five claims emerge from this study: (1) How do we reset the context of preaching? (2) How do we revise the present preaching theory of the Korean church? (3) How do we define and defend conversion preaching that is seemingly exclusive in contemporary pluralistic Korean society? (4) How do we rethink and re-establish the ecclesiology of the Korean church? (5) How do we formulate the Christian culture against or in the rage of worldly thoughts and cultures in Korea? This thesis concludes by proposing preaching as interaction and the preacher as an inter-actor between church and culture. Practical strategies are developed to answer the claims. / Thesis (PhD (Practical Theology))--University of Pretoria, 2005. / Practical Theology / unrestricted

Orientadora: Profa. Dra. Giselle Cerchiaro / Tese (doutorado) - Universidade Federal do ABC, Programa de Pós-Graduação em Biossistemas, Santo André, 2018. / Em doencas neurodegenerativas amiloidais o estresse oxidativo tem um papel importante juntamente com a proteina ¿À-amiloide (A¿À), associada a formacao de placas senis na Doenca de Alzheimer. Tais condicoes demonstraram desbalanco de metais, como cobre e zinco, tanto na concentracao celular e quanto nos processos antioxidantes. A Cu,Zn-Superoxido Dismutase (SOD1), em condicoes neurodegenerativas, pode demonstrar alteracoes estruturais e funcionais, tendo menor afinidade pelo cobre e pelo zinco. Diante destas condicoes, o objetivo principal desta tese foi em condicoes oxidativa (H2O2) e neurodegenerativa (A¿À1-42) avaliar os danos a biomoleculas, concentracao metais e a influencia da enzima SOD1 em linhagens de celulas neuronais (NSC-34 e mHippoE2). Diferentes respostas quanto a sensibilidade das linhagens neuronais foi observada durante as condicoes oxidativas e neurodegenerativa. Quanto os danos ao DNA a linhagem NSC-34 demonstrou maior sensibilidade a condicao oxidativa, com aumento de danos ao DNA, lesoes oxidativas em bases nitrogenadas que indicaram a presenca de lesoes tipo 8-oxo-G, corroborando com anormalidades nucleares e inibicao do processo de divisao celular. Nesta mesma linhagem quantidades aumentadas de Cu foram observadas, juntamente com a presenca da enzima SOD1 a nivel citoplasmatico e nuclear na condicao oxidativa (H2O2), alem de resultados significantes para danos permanentes ao DNA (anormalidades nucleares e quebras cromossomicas). A linhagem mHippoE2 apresentou aumentos significativos mediante a condicao oxidativa e neurodegenerativa, como oxidacao de proteinas e lipidios, demonstrando tambem alteracoes morfologicas citoplasmaticas. O tratamento com A¿À1-42 demonstrou aumento de danos ao DNA, lesoes oxidativas 8-oxo-G e tambem em bases purinicas. Podemos observar nesta mesma linhagem a forte influencia do Zn na condicao neurodegenerativa, atividade da SOD1 em ambas condicoes e tambem danos permanentes ao DNA mediante condicao neurodegenerativa. Dentre os resultados obtidos salientamos a relevancia dos achados na condicao neurodegenerativa ocasionada pelo peptideo A¿À1-42 nos ensaios para avaliacao genotoxica e mutagenica. Tal condicao demonstrou a presenca de danos importantes a bases nitrogenadas, tanto purinicas quando pirimidinicas, apontando tambem para possiveis efeitos mutagenicos detectados pelos eventos de quebras cromossomicas associados as anormalidades nucleares, bem como a presenca da enzima SOD1 no nucleo das celulas. / In neurodegenerative diseases, oxidative stress plays an important role associated with â-amyloid protein (Aâ), associated with the formation of amyloid plaques in Alzheimer's Disease (AD). In AD condition it has been demonstrated an imbalance of essential metals, such as copper and zinc, their cellular concentration and antioxidant processes alterations. The antioxidant enzyme Cu, Zn-Superoxide Dismutase (SOD1), under neurodegenerative conditions has structural and functional changes, such as lower affinity for copper and zinc. According to these conditions, the main objective of this thesis was to investigate how the oxidative (H2O2) and neurodegenerative (Aâ1-42) conditions cause biomolecules damage, metal alteration and SOD1 location in neuronal cell lines (NSC-34 and mHippoE2). Different responses in neuronal cell lines were observed during the conditions evaluated. For DNA damage, the NSC-34 cells demonstrated greater sensitivity to the oxidative condition, with increased DNA damage, oxidative lesions on nitrogenized bases indicating the presence of 8-oxo-G type lesions. In this same cell line we observed an increase of Cu amount, together with the presence of the SOD1 enzyme at the cytoplasmic and nuclear level in the oxidative condition (H2O2). The mHippoE2 cell line presented increased protein oxidation through the oxidative and neurodegenerative condition. Treatment with Aâ1-42 demonstrated increased DNA damage in this cell, 8-oxo-G oxidative lesions and also purine bases. We observed, in this same cell line, the strong influence of Zn on the neurodegenerative condition, SOD1 activity in both conditions and it was observed permanent damages to DNA in the neurodegenerative condition. Among the results, we highlight the relevance of the findings in the neurodegenerative condition caused by the Aâ1-42 peptide in the genotoxic and mutagenic evaluation trials. This condition demonstrated the presence of important damages to nitrogenated bases, both purine and pyrimidine, also pointing to possible mutagenic effects detected by the events of chromosomal breaks associated with nuclear abnormalities, as well as the translocation of the SOD1 enzyme to nuclei.

Kommunikation ist allgegenwärtig in unserem Alltag. Personen mit einer Autismus-Spektrum-Störung (ASS) zeigen soziale Schwierigkeiten und beim Erkennen von Kommunikationssignalen von Gesicht und Stimme. Da derartige Schwierigkeiten die Lebensqualität beeinträchtigen können, ist ein tiefgreifendes Verständnis der zugrundeliegenden Mechanismen von großer Bedeutung. In der vorliegenden Dissertation befasste ich mich mit sensorischen Gehirnmechanismen, die der Verarbeitung von Kommunikationssignalen zugrunde liegen und, die in der Forschung zu ASS bisher wenig Beachtung fanden. Erstens untersuchte ich, ob eine intranasale Gabe von Oxytocin die Erkennung der Stimmenidentität beeinflussen, und ihre Auffälligkeiten bei Personen mit ASS mildern kann. Zweitens erforschte ich, welche neuronalen Prozesse den Schwierigkeiten in der Wahrnehmung visueller Sprache in ASS zugrunde liegen, da bisherige Evidenz nur auf Verhaltensdaten basierte. Diese Fragestellungen beantwortete ich mit Hilfe von funktioneller Magnetresonanztomographie, Eyetracking und Verhaltenstestungen. Die Ergebnisse der Dissertation liefern neuartige Erkenntnisse, die für Personen mit ASS und typisch entwickelte Personen von hoher Relevanz sind. Erstens bestätigen sie die Annahmen, dass atypische sensorische Mechanismen für unser Verständnis der sozialen Schwierigkeiten in ASS grundlegend sind. Sie zeigen, dass atypische Funktionen sensorischer Gehirnregionen den Kommunikationseinschränkungen in ASS zugrunde liegen und die Effektivität von Interventionen beeinflussen, die jene Schwierigkeiten vermindern sollen. Zweitens liefern die Ergebnisse empirische Evidenz für theoretische Annahmen darüber, wie das typisch entwickelte Gehirn visuelle Kommunikationssignale verarbeitet. Diese Erkenntnisse erweitern maßgeblich unser aktuelles Wissen und zukünftige Forschungsansätze zur zwischenmenschlichen Kommunikation. Außerdem können sie neue Interventionsansätze zur Förderung von Kommunikationsfähigkeiten hervorbringen. / Communication is ubiquitous in our everyday life. Yet, individuals with autism spectrum disorder (ASD) have difficulties in social interactions and to recognize socially relevant signals from the face and the voice. Such impairments can vastly affect the quality of life - a profound understanding of the mechanisms behind these difficulties is thus strongly required. In the current dissertation, I focused on sensory brain mechanisms that underlie the perception of emotionally neutral communication signals that so far have gained little attention in ASD research. I studied the malleability of voice-identity processing using intranasal administration of oxytocin, and thus the potential to alleviate voice-identity recognition impairments in ASD. Furthermore, I investigated brain mechanisms that underlie recognition difficulties for visual speech in ASD, as until now evidence on visual-speech recognition in ASD was limited to behavioral findings. I applied methods of functional magnetic resonance imaging, eye tracking, and behavioral testing. The contribution of the present dissertation is twofold. First, the findings corroborate the view that atypical sensory perception is a critical cornerstone for understanding of social difficulties in ASD. Dysfunction of visual and auditory sensory brain regions might contribute to difficulties in processing aspects of communication signals in ASD and modulate the efficacy of interventions for improving the behavioral deficits. Second, the findings deliver empirical support for a recent theoretical model of how the typically developing brain perceives dynamic faces. This improved our current knowledge about brain processing of visual communication signals in the typically developing population. Advanced scientific knowledge about human communication, as provided in the current dissertation, propels further empirical research and development of clinical interventions that aim to promote communication abilities in affected individuals.

Les comportements sexuels problématiques (CSP) chez les enfants représentent une problématique complexe tant sur le plan de la recherche que de l’intervention clinique. L’hétérogénéité des enfants qui présentent des CSP est un défi sur les plans conceptuel et méthodologique. Alors que la recherche sur les facteurs associés aux CSP présentés par les enfants apparaît quelque peu limitée, plusieurs indices laissent supposer une association entre les CSP et les traits d’insensibilité émotionnelle. Ces traits sont caractérisés par un affect superficiel ainsi qu’un manque d’empathie et de remords. Seulement quelques études à ce jour ont exploré cette association et aucune n’a porté spécifiquement sur les enfants âgés de 6 à 12 ans. Les traits d’insensibilité émotionnelle sont importants à considérer puisqu’ils sont associés à la gravité des gestes d’agression chez les jeunes et à une résistance accrue à l’intervention. Objectifs. L’objectif général de ce mémoire est de mieux comprendre les facteurs associés à la variété des CSP. Plus précisément, nous voulons comprendre si et dans quelle mesure les traits d’insensibilité émotionnelle sont associés aux CSP. Nous avons donc proposé un modèle conceptuel adapté qui tient compte des traits d’insensibilité émotionnelle. Méthode. Notre échantillon est constitué de 90 dyades parent-enfant (M âge enfant = 9,1 ans ; É-T = 2,2 ; 36,7% filles) ayant reçu des services de psychothérapie pour leurs CSP au Centre d’expertise Marie-Vincent entre 2006 et 2010. Les participants ont complété une batterie d’évaluation incluant plusieurs instruments de mesure qui permettent de refléter l’ensemble des dimensions du modèle conceptuel. Un score de traits d’insensibilité émotionnelle a été dérivé à partir de divers instruments mesurant le comportement des enfants. Un modèle de régression linéaire hiérarchique a été élaboré afin d’estimer l’influence des traits d’insensibilité émotionnelle, en prenant en compte l’influence des autres variables individuelles et familiales. Résultats. Les résultats ont révélé que les traits d’insensibilité émotionnelle ne sont pas associés aux CSP des enfants lorsque leurs comportements extériorisés sont également pris en compte. Par ailleurs, la présence de comportements extériorisés et l’exposition à un cumul d’expériences de victimisation, excluant la victimisation sexuelle, étaient des facteurs associés à la variété des CSP. Il n’y avait également pas d’association significative entre la victimisation sexuelle et la variété des CSP. Conclusion. Les résultats appuient en partie le modèle conceptuel proposé. Des recherches reposant sur de plus grands échantillons devraient être effectuées pour mieux comprendre l’association entre les traits d’insensibilité émotionnelle et les CSP. Les résultats suggèrent néanmoins que les comportements extériorisés et les expériences de victimisation non sexuelles contribuent davantage à expliquer la variété des CSP chez les enfants référés pour une intervention que la victimisation sexuelle. / Sexual behavior problems (SBP) in children represent a complex issue both in terms of research and clinical intervention. The heterogeneity of children with SBP is a conceptual and methodological challenge. While research on the factors associated with SBP presented by children appears somewhat limited, there is some ground of belief in an association between SBP and callous-unemotional traits (e.g., superficial affect and lack of empathy and remorse). Few studies to date have explored this association, and none has focused specifically on children aged between 6 and 12 years old. These traits are important to consider because they are associated with the severity of aggression behaviors in youth and an increased resistance to intervention. Objectives. The main objective of this Masters’ thesis is to foster our understanding of the factors associated with the variety of SBP. Specifically, we want to understand if and to what extent callous-unemotional traits are associated with SBP. We have therefore proposed an adapted conceptual model that takes into account callous-unemotional traits. Method. Our sample consists of 90 parent-child dyads (M child’s age = 9.1 years ; SD = 2.2 ; 36.7% girls), who received psychotherapy services for SBP at the Marie-Vincent Center between 2006 and 2010. Participants completed an assessment battery including several instruments that reflect all the dimensions of the conceptual model. A score of callous-unemotional traits was derived from various instruments measuring children's behavior. A hierarchical linear regression model was developed to estimate the influence of callous-unemotional traits, taking into account the influence of the individual and family variables. Results. Results revealed that callous-unemotional traits were not associated with children's SBP when their externalized behaviors were taken into account. In addition, the presence of externalized behaviors and exposure to a combination of victimization experiences, excluding sexual victimization, were associated with the variety of SBP. There was also no significant association between sexual victimization and the variety of SBP. Conclusion. The results partially support the proposed conceptual model. Research with larger samples should be done to better understand the influence of callous-unemotional traits on SBP. The results suggest, however, that externalized behaviors and non-sexual victimization experiences are more important in explaining the variety of SBP of children referred for an intervention than sexual victimization.