Orientador: Alzir Azevedo Batista / Banca: Luiz Antônio Andrade de Oliveira / Banca: Regina Frem / Banca: Wagner Ferraresi de Giovani / Banca: Benedito Lima Neto / Resumo: O complexo inédito mer-[RuCl3(dppb)H2O], foi caracterizado como precursor de uma série de compostos fosfínicos. Foram testadas sínteses do complexo título com ligantes providos de diferentes modos de coordenação, tais como os monodentados (L= DMSO, MeOH, NO e CO, py, 4-Mepy), exodentado (L= 4-CNpy), bidentados (L-L= 2,2'-bipy, fen) e ambidentado (L-L= 4,4'-bipy). Os produtos destas reações foram isolados como espécies bifosfínicas de rutênio (III) de fórmula geral mer-[RuCl3(dppb)(L)], cis-[RuCl2(dppb)(L-L)]+ e [Ru2Cl6(dppb)2(μ-4,4'-bipy)]. Reações do mer-[RuCl3(dppb)H2O] e fosfinas mono, bi e tridentadas, foram investigadas e a partir destas, obteve-se a série de complexos mono, bi e trifosfínicos de rutênio (II), conhecidos na literatura como reagentes para sínteses de compostos de rutênio, tais como [RuCl2(dppb)(PPh3)], [RuCl2(P-P)2] (P-P= dppm, dppe e dppp) e [Ru2Cl4(P-P)3] (PP= dppb), e [Ru2Cl3(P-P-P)2]Cl (P-P-P= tdpme e etp). A partir dos complexos do tipo [Ru2Cl3(P-P-P)2]Cl, obteve-se compostos do tipo [RuCl(P-P-P)(N-heterocíclico)]Cl, dando continuidade à nova série de complexos mononucleares solvato, [RuCl(P-P-P)(solvente)]Cl. Os compostos de Ru(II) e Ru(III) obtidos, foram caracterizados através de espectroscopia de absorção na região do infravermelho, ultravioleta-visível, RPE, RMN 31P, medidas de condutância molar, medidas de susceptibilidade magnética, análise elementar, voltametria cíclica e em alguns casos, difração de raios-X. O comportamento eletroquímico dos complexos bifosfínicos de Ru(III) mer- [RuCl3(dppb)H2O] e mer-[RuCl3(dppb)(L)], apresentou perfil bastante peculiar. A partir da metodologia empregada na obtenção por via eletroquímica, atribuiu-se as espécies Ru2II/III, [Ru2Cl5(dppb)2], de Ru(II), [Ru2Cl4(dppb)2], [RuCl2(dppb)(L)2] e [Ru2Cl4(dppb)2(L)], como produtos formados na superfície do eletrodo,...(Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The new complex mer-[RuCl3(dppb)H2O] was characterized as precursor of a series of ruthenium (III) mono and biphosphines complexes. Syntheses of the complex title were tested with ligands provided from different coordination manners, such as the monodentates ligands (L = DMSO, MeOH, NO, CO, py, 4-Mepy), exobidentate ligand (L = 4-CNpy), chelate ligands (L-L = 2,2'-bipy, fen) and umbidentate ligand (L-L = 4,4'-bipy). The reaction products were isolated as ruthenium (III) phosphines complexes of general formula mer-[RuCl3(dppb)(L)], cis-[RuCl2(dppb)(L-L)]+, and [Ru2Cl6(dppb)2(μ-4,4'-bipy)], respectively. Reactions of the mer-[RuCl3(dppb)H2O] with monophosphines, diphosphines and triphosphines were investigated and starting from these, it was obtained the series of complex mono, di and triphosphines ruthenium (II), wich are known in the literature as starting material for syntheses of compounds of ruthenium, such as [RuCl2(dppb)(PPh3)], [RuCl2(P-P)2] (P-P = dppm, dppe and dppp) and [Ru2Cl4(P-P)3] (P-P = dppb), and [Ru2Cl3(PP- P)2]Cl (P-P-P = tdpme and etp). Mononuclear ruthenium complexes of the type [RuCl(P-PP)( N-heterocylic)]Cl, were isolated from the reaction of the binuclear [Ru2Cl3(P-P-P)2]Cl (PP- P = tdpme and etp) with excess of ligand. Standard spectroscopic methods, particularly IR, UV-Vis, EPR, 31P{1H} MNR, were extensively used to characterize (sometimes in conjunction with X-ray crystallography) all of the species discussed in this thesis. The complexes were also characterized by molar conductance, magnetic moment measurement, elementary analysis and cyclic voltammetry. The electrochemical behaviour of the biphosphine complexes Ru(III) presented quite peculiar profiles. Starting from the methodology using electrochemistry route, it was attributed the species of Ru2II/III, [Ru2Cl5(dppb)2], and of Ru(II), [Ru2Cl4(dppb)2], [RuCl2(dppb)(L)2] and [Ru2Cl4(dppb)2(L)], ...(Complete abstract, click electronic access below) / Doutor

A obesidade e a resistência à insulina induzidas por dieta têm sido associadas ao aumento da morte de neurônios dopaminérgicos e depleção da dopamina (DA) nigroestriatal em modelo animal da Doença de Parkinson (DP), sugerindo uma maior vulnerabilidade dos neurônios dopaminérgicos em resposta a perturbações metabólicas. No entanto, ainda não há evidências consistentes que demonstrem uma associação linear entre a obesidade e a morte de neurônios dopaminérgicos e os mecanismos subjacentes que podem estar contribuindo para o desenvolvimento da DP. Para avaliar se a obesidade promove neurodegeneração dopaminérgica e/ou alterações nos parâmetros relacionados com a progressão da DP, ratos Wistar machos receberam uma dieta padrão ou uma dieta rica em gordura (HFD) durante vinte e cinco semanas e a substantia nigra, estriado e a área tegmental ventral foram isolados e submetidos a análises bioquímicas. Em conformidade com a ingestão calórica, os ratos HFD apresentaram aumento da massa gorda e peso corporal total associados à intolerância à glicose e resistência à insulina A obesidade induzida por dieta diminuiu os níveis de tirosina hidroxilase (TH) indicando perda de neurônios dopaminérgicos e também promoveu alterações no imunoconteúdo de sinaptofisina relacionadas com a inflamação periférica e central indicadas pelo aumento de TNF-α e IL1β bem como estresse oxidativo/nitrosativo com aumento da nitração de tirosina e oxidação de grupos sulfidril. Nenhuma diferença foi detectada para o imunoconteúdo de α-syn e p-Tau entre os grupos. Além disso, níveis reduzidos de TH foram confirmados na análise de imunofluorescência, bem como morte neuronal e ativação de microglia indicados pela diminuição de NeuN e aumento de Iba1 sem haver alterações para GFAP. Adicionalmente, foram identificadas piora da atividade locomotora, mobilidade e evidências apontando para um comportamento do tipo ansiolítico nas tarefas de campo aberto e claro / escuro. Não houve alterações na coordenação motora e memória. Juntos, estes dados sugerem que a obesidade induzida pela dieta hiperlipídica de fato promove a morte de neurônios dopaminérgicos na via nigroestriatal independentemente de α-syn e fosforilação da Tau. O aumento da morte neuronal pode ser atribuído à inflamação cerebral e estresse oxidativo / nitrosativo induzido pela obesidade, o que possivelmente levou às alterações comportamentais observadas neste estudo. / Diet-induced obesity and insulin resistance has been associated to increased dopaminergic neurodegeneration and nigrostriatal dopamine (DA) depletion in animal model of Parkinson’s Disease (PD), suggesting an enhanced vulnerability of dopaminergic neurons in response to metabolic perturbation. However, there is still no consistent evidence demonstrating a linear association between obesity and dopaminergic neurons death and the underlying mechanisms that can be contributing to the development of PD. In order to evaluate whether obesity promotes dopaminergic neurodegeneration and / or changes in parameters related to PD progression, male Wistar rats were fed with standard chow or high-fat diet (HFD) for twenty five weeks and the brain substantia nigra, striatum and ventral tegmental area were isolated before undergoing biochemical analyzes. In accordance with energy intake, the HFD rats showed increased fat mass and total body weight associated to glucose intolerance and insulin resistance. Diet-induced obesity decreases tyrosine hydroxylase (TH) levels indicating dopaminergic neurons loss and also promoted changes in the synaptophysin immunocontent related to peripheral and brain inflammation with increased TNF-α and IL1β, as well oxidative/nitrosative stress with increased tyrosine nitration and oxidation of sulfhydryl groups No difference was detected for α-syn and p-Tau immunocontent between groups. Moreover, decreased levels of TH were confirmed in the immunofluorescence analysis, as well neuronal death and microglia activation with NeuN and Iba1 without changes for GFAP. In addition, impairment of locomotor activity, mobility and evidences pointing for an anxiolytic-like behavior were identified in the open-field and light/dark tasks. There were no changes in the motor coordination and memory. Together, these data suggest that diet-induced obesity indeed promotes dopaminergic neurodegeneration in the nigrostriatal pathway independent of α-syn and phosphorylation of Tau. The increased neuronal death can be attributed to the brain inflammation and oxidative/nitrosative stress induced by obesity, which would likely lead to behavioral changes observed in this study.

En vue d’effectuer des préparations sélectives de composés hétérocycliques, une étude de la synthèse et de la réactivité de 7-oxanorborna-2,5-diènes portant des groupes électroattracteurs différents sur les positions 2 et 3 a été réalisée. Ces composés sont des formes masquées de composés acétyléniques dissymétriques.Dans un premier temps, nous avons optimisé une nouvelle méthode de synthèse sélective d’acétylènedicarboxylates dissymétriques par mono-transestérification d’acétylènedicarboxylates de dialkyle symétriques avec des alcools en présence de la lipase de Candida rugosa. Cette méthode nous a permis d’obtenir les diesters dissymétriques avec de bons rendements et une haute sélectivité a priori inattendue.Dans un second temps, nous avons développé des synthèses régiosélectives de dérivés de l’acide 7-oxanorborna-2,5-diène-2,3-dicarboxylique selon deux stratégies. Dans une première approche, une réaction de Diels-Alder intramoléculaire entre un furane et un composé acétylénique reliés par une agrafe siliciée a été réalisée, suivie d’une coupure des liaisons Si-C. Cette cycloaddition [4+2] s’effectue uniquement en présence de MeAlCl2 avec des rendements moyens. Dans certains cas, la coupure des liaisons Si-C conduit aux diesters désirés. Dans une deuxième approche, une mono-saponification d’oxanorbornadiène-2,3-dicarboxylates de dialkyle a permis d’accéder régiosélectivement à des monoacides et des réactions de couplage avec des amines ou des alcools ont conduit sélectivement à des dérivés présentant deux groupes électroattracteurs différents.Dans une dernière partie, nous avons effectué la préparation régiosélective de 3-pyrrolines par cycloaddition [2+3] d’un ylure d’azométhine suivie d’une réaction de rétro-Diels-Alder à partir des 7-oxanorbornadiènes comportant deux groupes électroattracteurs différents. La préparation aisée de 3-pyrrolines condensées non décrites dans la littérature a été obtenue par formation inattendue d’un motif succinimide dans le cas des amidoesters.En conclusion, il apparaît que la présence du groupe éthyle en tête de pont des 7-oxanorborna-2,5-diènes semble suffisante pour contrôler la régiosélectivité de ces cycloadditions. / In order to selectively prepare heterocyclic compounds, a study of the synthesis and reactivity of 7-oxanorborna-2,5-dienes with different electron-withdrawing groups on the 2 and 3 positions was performed. These compounds are masked forms of unsymmetrical acetylenic compounds. At first, we have optimized a new method for the selective synthesis of unsymmetrical diesters by transesterification of symmetrical dialkyl acetylenedicarboxylates in the presence of Candida rugosa lipase. This unexpectedly highly selective method allowed us to obtain unsymmetrical acetylenedicarboxylates in good yields.In a second part, we have developed a regioselective synthesis of 7-oxanorborna-2,5-diene-2,3-dicarboxylic acid derivatives according to two strategies. In one approach, an intramolecular Diels-Alder reaction between a furan and an acetylenic compound connected by silicon-containing tethers was performed, followed by a cleavage of the Si-C bonds. This [4+2] cycloaddition was carried in the presence of a Lewis acid, only MeAlCl2 gave the expected product and so in moderate yields. In most cases, the cleavage of Si-C bonds leads to the desired diesters. In a second approach, a mono-saponification of dialkyl oxanorbornadiene-2,3-dicarboxylates provided access regioselectively to mono-acids and coupling reactions with amines or alcohols selectively led to poly-functionalized products containing two different electron-withdrawing groups.In the last part, we have regioselectively prepared 3-pyrrolines by [2+3] cycloaddition of an azomethine ylide to 7-oxanorbornadienes bearing electroattracting groups followed by a retro-Diels-Alder reaction. An easy synthesis of previously unknown condensed 3-pyrrolines was obtained by formation of an unexpected succinimide pattern from amidoesters. In conclusion, it appears that the presence of an ethyl group on the bridgehead carbon atom of 7-oxanorborna-2,5-dienes seems sufficient to control the regioselectivity of these cycloadditions.

Marcos Roberto da Silva Tavares / Dissertação (mestrado) - Universidade Federal do ABC, Programa de Pós-Graduação em Física, 2013

Das elementare Kennzeichen der eukaryontischen Zelle ist der Zellkern, in welchem die Erbinformation in Form der DNA vorliegt. Dieser ist von einer äußeren Kernhülle umgeben, welche kontinuierlich in das endoplasmatische Retikulum übergeht. An der inneren Kernhülle setzt die Kernlamina an. Unterbrochen wird die Kernhülle durch die Kernporen. Diese bestehen aus Untereinheiten, welche als Nukleoporine bezeichnet werden. Eine wesentliche Aufgabe der Kernporen ist der Transport von Makromolekülen, welche durch spezifische Transportsignalsequenzen gekennzeichnet sind. Es mehren sich die Hinweise, dass die Nukleoporine nicht allein für den Kerntransport verantwortlich sind, sondern auch regulatorische Eigenschaften bei Mitose, der Expression von Proteinen und der Stabilisierung des Genoms übernehmen. Nach der Entdeckung der Philadelphia Translokation bei der chronisch myeloischen Leukämie wurden eine Reihe weiterer chromosomaler Translokationen im Rahmen von hämatologischen Neoplasien beschrieben. Hierbei sind auch Nukleoporine involviert. Es entstehen Fusionsproteine, welche ein neues Verteilungsmuster der Proteine erzeugen und möglicherweise auch neue Funktionen innehaben. Nup214/CAN ist ein Onkogen, welches in akuten myeloischen Leukämien mit einer chromosomalen Translokation einhergeht t(6;9). Diese Translokation t(6;9) ist mit einer schlechteren Prognose für den Patienten verbunden. Der genaue onkogene Mechanismus ist noch nicht ausreichend verstanden. Ziel dieser Doktorarbeit war die Frage, welches Verteilungsmuster Nup214 als Fusionsprotein mit einer veränderten NLS in Leukämiezellen der chromosomalen Translokation t(6;9) aufweist, zu beantworten. Zu diesem Zweck wurden die Fusionsproteinfragmente DEK, CAN Mitte und CAN 80/81 in E. coli exprimiert, aufgereinigt und der Herstellung eines spezifischen Antikörpers zugeführt. Hierzu wurden die mit den Proteinfragmenten transfizierten E. coli amplifiziert. Nach Lyse der Zellen wurden die Proteinfragmente elektrophoretisch getrennt und den ermittelten Molekulargewichten zugeordnet. Mit Hilfe einer Affinitätschromatographie und einem Proteintransfer auf Nitrozellulosemembran wurde mit polyvalentem Serum eine Affinitätsreinigung des Antikörpers durchgeführt. Dadurch konnten spezifische Antikörper generiert werden, welche in der Immunfloureszenz die physiologischen Verteilungsmuster zeigten. In einem nachfolgenden Schritt konnte in Kooperation mit dem Biologischen Institut Basel mittels Immuno-Gold-Lokalisation von Nup214/CAN in Leukämiezellen mit einer chromosomalen Translokation t(6;9) erstmalig die Lokalisation des Proteins auf zytoplasmatischer und nukleoplasmatischer Seite einer Kernpore gezeigt werden. Dies legt die Vermutung nahe, dass es durch diese Mislokalisation zu einer Störung des nukleären Transports kommen kann, der wiederum zu einem Wachstumsvorteil oder einer Inhibition der Apoptose der Leukämiezellen führt. / The cell nucleus is the fundamental hallmark in eukaryotic cells. It is surrounded by the outer nuclear membrane, which pass into the endoplasmic reticulum. The inner nuclear membrane is lined with the lamina. Nuclear pore complexes interrupt the nuclear membrane. Subunits are called nucleoporines. One major task is the transport of macromolecules with a determined transport sequence. There is evidence, that nucleoporines are not only responsible for the nucleocytoplasmatic transport. They are also involved in mitosis, stabilisation of the genome or protein expression. After discovery of the Philadelphia translocation in chronic myeloid leukaemia a number of other chromosomal translocation in haematological neoplasm were depicted. New types of fusion proteins Nucleoporines are described, which have a new distribution pattern and also might have new functions. The nuclear pore protein Nup214/CAN is an oncogene in acute myeloid leukaemia characterized by a (6;9)(p23;q34) chromosomal translocation. The detailed oncogenic mechanism is still not well known. The objective of this thesis was the distribution pattern of Nup214 in leukaemoid blasts. For this purpose fragments of the fusion protein DEK, CAN Mitte, and CAN 80/81 were expressed in E.coli in order to generate a specific purified antibody. For this transfected E.coli were multiplied. After lysis protein fragments of the fusion protein were electrophoretically separated and then matched to the calculated molecular weight. After affinity chromatographic purification and protein transfer via Western Blot affinity purification was performed. With this procedure affinity purified antibodies were assembled. In cooperation with the Biological Institute Basel, Switzerland in leukaemia cells with a (6;9)-translocation, but not in controll cells, antibodies labelled both sides of the nuclear pore complex, indicating a localization of the oncogenic DEK-CAN fusion protein on the nucleoplasmic side of the NPC. This can be seen to imply, that mislocalization of Nup214/CAN in the fusion protein to the nucleoplasmic surface of the pore might disturb transport equilibrium and therefore benefit cell growth or lead to inhibition of apoptosis.

本論旨在透過包含「mono」「koto」的述語句之分析整理，究明形式名詞「mono」「koto」的性質。 首先自青空文庫、每日新聞、新潮文庫等三項語料庫收集「mono」「koto」的例句，從中整理出以下五組「mono」「koto」的類義句型。 經驗：「-rukoto ga atta」「-tamonoda」 思慮：「koto to omou」「mono to omou」 感嘆：「koto」「-(ta)monoda」 應當：「kotoda」「monoda」 期望：「dekirukotonara」「dekirumononara」 本論假設以上五組類義句型，其意義之所以存在相異之處，乃出自於「mono」「koto」之影響，將五組句型分為五個章節加以論述。 分析的結果簡述如下： 　表經驗的句型中，「-rukoto ga atta」表示的為偶發經驗，「-tamonoda」則是重複頻率更高的習慣性經驗。 　表思慮的句型中，「koto to omou」表推測，多帶有體諒的語氣。其原因在分析後得知來自於「koto」的移動性。「mono to omou」的語意在「堅信」與「推理的結論」間游移。其原因在於是否將結論的證據放置在前後文中。 　表感嘆的句型中，「koto」表即時性的感嘆，少用於主題句中。而「-(ta)monoda」表示回顧式的感嘆，主題句中亦可使用。 表應當的句型中，「kotoda」是針對特定的事項表示應當的語意。「monoda」方面，否定形式的「monodehanai」依動詞的種類，在「否定的性質」與「非應當」兩種語意間形成相輔分布。而「~naimonoda」則不論動詞種類為何，皆傾向於「否定的性質」的表示。 表期望的句型中，「dekirumononara」是表示該願望實現可能性極低的文法句型，而「dekirukotonara」則是具有實際意義的名詞「koto」加上修飾詞語的子句。 最後，在總節各章節的分析之後，可得到以下的結論：「koto」具有動態性質，時間內含其中。而「mono」則具有靜態性質，乃是將時間加以捨象的存在。

Cette thèse traite de l'estimation de la concentration dans le sang artériel de molécules marquées par un radioélément émettant des positons. Cette concentration est appelée « fonction d'entrée artérielle B+ ». Elle doit être déterminée dans de nombreuses analyses en pharmacocinétique. Actuellement, elle est mesurée à l'aide d'une série de prélèvements artériels, méthode précise mais nécessitant un protocole contraignant. Des complications liées au caractère invasif de la méthode peuvent survenir (hématomes, infections nosocomiales).L'objectif de cette thèse est de s'affranchir de ses prélèvements artériels par l'estimation non-invasive de la fonction d'entrée B+ à l'aide d'un détecteur externe et d'un collimateur. Cela permet la reconstruction des vaisseaux sanguins afin de discriminer le signal artériel du signal contenu dans les autres tissus avoisinants. Les collimateurs utilisés en imagerie médicale ne sont pas adaptés à l'estimation de la fonction d'entrée artérielle B+ car leur sensibilité est très faible. Pour cette thèse, ils sont remplacés par des collimateurs codés, issus de la recherche en astronomie. De nouvelles méthodes pour utiliser des collimateurs à ouverture codée avec des algorithmes statistiques de reconstruction sont présentées.Des techniques de lancer de rayons et une méthode d'accélération de la convergence des reconstructions sont proposées. Une méthode de décomposition spatio-temporelle est également mise au point pour estimer efficacement la fonction d'entrée artérielle à partir d'une série d'acquisitions temporelles.Cette thèse montre qu'il est possible d'améliorer le compromis entre sensibilité et résolution spatiale en tomographie d'émission à l'aide de masques codés et d'algorithmes statistiques de reconstruction ; elle fournit également les outils nécessaires à la réalisation de tellesreconstructions.

<p>Oscillator strengths and transition energies are calculated for several mono-substitutes of benzene and naphthalene molecules. The substituents investigated are chlorine, bromine and iodine. Calculations for these molecules are presented, at the Hartree-Fock and DFT level of theory. The functional used in DFT is CAM-B3LYP.</p>

<p>The field of autonomous vehicle navigation and localization is a highly active research</p><p>topic. The aim of this thesis is to evaluate the feasibility to use outdoor visual navigation in a semi-structured environment. The goal is to develop a visual navigation system for an autonomous golf ball collection vehicle operating on driving ranges.</p><p>The image feature extractors SIFT and PCA-SIFT was evaluated on an image database</p><p>consisting of images acquired from 19 outdoor locations over a period of several weeks to</p><p>allow different environmental conditions. The results from these tests show that SIFT-type</p><p>feature extractors are able to find and match image features with high accuracy. The results also show that this can be improved further by a combination of a lower nearest neighbour threshold and an outlier rejection method to allow more matches and a higher ratio of correct matches. Outliers were found and rejected by fitting the data to a homography model with the RANSAC robust estimator algorithm. </p><p>A simulator was developed to evaluate the suggested system with respect to pixel noise from illumination changes, weather and feature position accuracy as well as the distance to features, path shapes and the visual servoing target image (milestone) interval. The system was evaluated on a total of 3 paths, 40 test combinations and 137km driven. The results show that with the relatively simple visual servoing navigation system it is possible to use mono-vision as a sole sensor and navigate semi-structured outdoor environments such as driving ranges.</p>

Oscillator strengths and transition energies are calculated for several mono-substitutes of benzene and naphthalene molecules. The substituents investigated are chlorine, bromine and iodine. Calculations for these molecules are presented, at the Hartree-Fock and DFT level of theory. The functional used in DFT is CAM-B3LYP.