Li-O2 batteries have been attracting increasing attention and R&D efforts as promising power sources for electric vehicles (EVs) due to their significantly higher theoretical energy densities compared to conventional Li-ion batteries. The research presented in this thesis covers the investigation of factors influencing the decomposition of Li2O2, the development of highly active electrocatalysts, and the design of low-cost and easy-operation binder-free O2 electrodes for Li-O2 batteries. Being the main technique, SR-PXD was used both as a continuous light source to advance the electrochemical decomposition of Li2O2 under the X-ray illumination and an operando tool that allowed us to probe the degradation of Li2O2. Since XRD was intensively used in my thesis work, the effect of X-ray irradiation on the stability of Li2O2 was studied. The accelerating effect of X-rays on the electrochemical decomposition of Li2O2 was, for the first time, explored. The electrochemical decomposition rate of Li2O2 was proportional to the X-ray intensity used. It is proposed that the decomposition might involve a three-step reaction with [Li2O2]x+ and Li2-xO2* as intermediates, which followed pseudo-zero-order kinetics. Then, three electrocatalysts (Pt/MNT, Ru/MNT and Li2C8H2O6) were developed, which exhibited good electrocatalytic performances during the OER. Their activities were evaluated by following the Li2O2 decomposition in electrodes during the charging processes. In addition, the time-resolved OER kinetics for the electrocatalyst-containing Li-O2 cells charged galvanostatically and potentiostatically was systematically investigated using operando SR-PXD. It was found that a small amount of Pt or Ru decoration on the MNTs enhanced the OER efficiency in a Li-O2 cell. The Li2O2 decomposition of an electrode with 5 wt% Pt/MNT, 2 wt% Ru/MNT or Li2C8H2O6 in a Li-O2 cell followed pseudo-zero-order kinetics. Finally, a novel binder-free NCPE for Li-O2 batteries was presented. It displayed a bird’s nest microstructure, which could provide the self-standing electrode with considerable mechanic durability, fast O2 diffusion and enough space for the discharge product deposition. The NCPE contained N-containing functional groups, which may promote the electrochemical reactions.

This paper reports the development of an Alkali Activated Binder (AAB) with an emphasis on the performance and the durability of the AAB-matrix. For the development of the matrix, the reactive components granulated slag and coal fly ash were used, which were alkali activated with a mixture of sodium hydroxide (2 - 10 mol/l) and aqueous sodium silicate solution (SiO2/Na2O molar ratio: 2.1) at ambient temperature. A sodium hydroxide concentration of 5.5 mol/l revealed the best compromise between setting time and mechanical strengths of the AAB. With this sodium hydroxide concentration, the compressive and the 3-point bending tensile strength of the hardened AAB were 53.4 and 5.5 MPa respectively after 14 days. As a result of the investigation of the acid resistance, the AAB-matrix showed a very high acid resistance in comparison to ordinary Portland cement concrete. In addition, the AAB had a high frost resistance, which had been validated by the capillary suction, internal damage and freeze thaw test with a relative dynamic E-Modulus of 93% and a total amount of scaled material of 30 g/m2 after 28 freeze-thaw cycles (exposure class: XF3).

L’infertilité affecte jusqu’à 15-20% des couples en âge de se reproduire. C’est pourquoi, mieux comprendre les mécanismes à la base de la fécondation est essentiel pour l’identification de nouvelles causes d’infertilité et l’optimisation des techniques de reproduction assistée. La capacitation est une étape de la maturation des spermatozoïdes qui se déroule dans le tractus génital femelle. Elle est requise pour la fécondation d’un ovocyte. Notre laboratoire a démontré que des protéines du plasma séminal bovin, appelées protéines Binder of SPerm (BSP), se lient aux phospholipides portant des groupements choline à la surface de la membrane des spermatozoïdes lors de l’éjaculation et promeuvent la capacitation. Ces protéines exprimées par les vésicules séminales sont ubiquitaires chez les mammifères et ont été étudiées chez plusieurs espèces dont l’étalon, le porc, le bouc et le bélier. Récemment, l’expression de gènes homologues aux BSP a été découverte dans les épididymes d’humains (BSPH1) et de souris (Bsph1 et Bsph2). Notre hypothèse est que les BSP chez ces deux espèces sont ajoutées aux spermatozoïdes lors de la maturation épididymaire et ont des rôles dans les fonctions spermatiques, similaires à ceux des protéines BSP bovines. Les protéines BSP humaines et murines représentent une faible fraction des protéines totales du plasma séminal. Pour cette raison, afin d’étudier leurs caractéristiques biochimiques et fonctionnelles, des protéines recombinantes ont été produites. Les protéines recombinantes ont été exprimées dans des cellules Escherichia coli origami B(DE3)pLysS en utilisant un vecteur d’expression pET32a. Suivant la lyse cellulaire, les protéines ont été dénaturées avec de l’urée et purifiées par chromatographie d’affinité sur ions métalliques immobilisés. Une fois liées à la colonne, les protéines ont été repliées à l’aide d’un gradient d’urée décroissant avant d’être éluées. Cette méthode a mené à la production de trois protéines recombinantes (rec-BSPH1 humaine, rec-BSPH1 murine et rec-BSPH2 murine) pures et fonctionnelles. Des expériences de chromatographie d’affinité et de co-sédimentation nous ont permis de démontrer que les trois protéines peuvent se lier à des ligands connus des protéines BSP comme la gélatine et l’héparine en plus de pouvoir se lier aux spermatozoïdes. Nos études ont également révélées que les deux protéines rec-BSPH1 peuvent se lier aux liposomes de phosphatidylcholine (PC) et sont capable de promouvoir la capacitation des spermatozoïdes. À l’opposé, rec-BSPH2 ne peut ni se lier aux liposomes de PC, ni stimuler la capacitation. Finalement, les protéines recombinantes n’ont aucun effet sur la réaction acrosomique ou sur la motilité des spermatozoïdes. Chez les bovins, les protéines BSP induisent la capacitation grâce des interactions avec les lipoprotéines de haute densité (HDL) et les glycosaminoglycanes. Puisque le HDL est également un joueur important de la capacitation chez la souris, le rôle de la protéine native BSPH1 murine au niveau de la capacitation induite par le HDL a été étudié. Les résultats obtenus suggèrent que, in vivo, la protéine BSPH1 de souris serait impliquée dans la capacitation via une interaction directe avec le HDL. Comme les protéines BSPH1 humaines et murines sont orthologues, ces résultats pourraient aussi s’appliquer à la fertilité humaine. Les résultats présentés dans cette thèse pourraient mener à une meilleure compréhension de la fertilité masculine et aider à améliorer les techniques de reproduction assistée. Ils pourraient également mener au développement de nouveaux tests diagnostiques ou de contraceptifs masculins. / Infertility can affect as much as 15-20% of couples of reproductive age. Therefore, elucidating mechanisms occurring during fertilization is needed to resolve cases of infertility and optimize assisted reproductive technology procedures. Sperm capacitation is a maturation step that takes place in the female genital tract and is deemed to be essential for sperm to fertilize an oocyte. Our laboratory has demonstrated that proteins from bovine seminal plasma called Binder of SPerm (BSP) proteins bind to choline phospholipids on the sperm membrane upon ejaculation and promote capacitation. These proteins expressed in seminal vesicles are ubiquitous amongst mammals and have been studied in many species including stallion, boar, ram and goat. More recently, the expression of BSP-homologous genes has been discovered in the epididymis of humans (BSPH1) and in mice (Bsph1 and Bsph2). We hypothesized that the BSP homologs in these two species are added to sperm during epididymal maturation and play similar roles in sperm functions as bovine BSP proteins. BSP proteins in humans and mice constitute only a minute percentage of the seminal plasma proteins. Thus, to study their biochemical and functional characteristics recombinant proteins were produced. Recombinant proteins were expressed in Escherichia coli origami B(DE3)pLysS cells using a pET32a expression vector. Following cell lysis, proteins were denatured using urea and purified by immobilized metal ion affinity chromatography. Once bound to the resin, proteins were refolded using a decreasing urea gradient after which they were eluted. This method led to the production of three pure, functional recombinant proteins (human rec-BSPH1, mouse rec-BSPH1 and mouse rec-BSPH2). Using affinity chromatography and co-sedimentation experiments, we were able to demonstrate that all three recombinant proteins bind known ligands of BSP proteins including gelatin, heparin and have the ability to bind to sperm. Studies also revealed that both rec-BSPH1 proteins bind to phosphatidylcholine (PC) liposomes and promote sperm capacitation. However, rec-BSPH2 neither binds to PC liposomes nor stimulates capacitation. Recombinant proteins had no effect on acrosome reaction or sperm motility. In bovine, BSP proteins promote sperm capacitation through interactions with high-density lipoproteins (HDL) and glycosaminoglycans. Since in mice HDL is also a major factor implicated in capacitation, the role of the native murine BSPH1 protein in HDL-induced capacitation was investigated. Results obtained suggest that, in vivo, murine BSPH1 protein could act in capacitation via a direct interaction with HDL. As human and murine BSPH1 are orthologs, these results could possibly also apply to human fertility. The results presented in this thesis could lead to a better understanding of male fertility and help improve assisted reproduction technology procedures. They could also lead to the development of diagnostic tests as well male contraceptives.

Fast and precise quantification of circulating tumour cells (CTC) in lung adenocarcinoma is a pivotal step in acceleration of diagnosis, selection of early therapy and estimation of treatment prognosis. Development of a new type of microfluidic device based on detection and quantification of epithelial- and mesenchymal-type CTC by high-affinity and cell-type specific protein binders anchored to a microfluidic chip surface represents a highly innovative approach. In this work, we used EpCAM membrane glycoprotein as a target for generation of epithelial cell-specific protein binders by a directed evolution of proteins selected from highly complex combinatorial libraries derived from albumin-binding domain scaffold (ABD) or human muscle protein domain-derived "Myomedin" scaffold. Collections of EpCAM-binding candidates from the both used libraries were generated and particular binding variants were further characterized by DNA sequencing, biochemically and by functional cell-surface binding assays. The best candidates might serve as robust anchor proteins of a microfludic chip. Key words: epithelial cell, EpCAM, protein binder, ribosome display, combinatorial library, protein scaffold

Aditivos têm sido incorporados ao ligante asfáltico no intuito de melhorar o desempenho dos pavimentos. O enrijecimento do ligante asfáltico provocado pelos aditivos, aumenta a resistência à deformação permanente das misturas asfálticas, mas ainda não se sabe qual o efeito deles sobre a resistência à fadiga e ao trincamento térmico dos ligantes asfálticos. Um dos produtos modernos mais promissores para modificação de ligantes asfálticos é o ácido polifosfórico (PPA). No entanto, o mecanismo de modificação com PPA depende fortemente da composição química do ligante asfáltico de base. Para avaliar o impacto da adição de PPA em ligantes asfálticos de diferentes fontes, dois ligantes asfálticos 50/70 (REDUC e LUBNOR), de diferentes PGs e composição química foram modificados por quatro proporções de PPA (0,5, 1,0, 1,5, 2,0%). As frações de saturados, aromáticos, resinas e asfaltenos (SARA) dos ligantes asfálticos puros e modificados foram determinadas por meio da cromatografia de camada fina. Para avaliar o efeito da adição de PPA sobre as propriedades reológicas dos ligantes asfálticos, foram analisados a viscosidade, o grau de desempenho, a rigidez, a elasticidade, a recuperação elástica, a compliância não-recuperável e o comprimento de trinca na ruptura. A viscosidade dos ligantes asfálticos e as temperaturas de usinagem e compactação aumentaram com o aumento do teor de PPA. A temperatura alta do PG aumentou com a proporção de PPA em intensidades diferentes, dependendo do ligante asfáltico de base. A adição de PPA aumenta a rigidez, a elasticidade e a recuperação elástica e diminui a compliância não-recuperável dos ligantes asfálticos. Em termos de tolerância à fadiga, a adição de PPA e o envelhecimento provocaram um aumento na tolerância à fadiga dos ligantes asfálticos. Os resultados apresentados destacam a importância da composição química do ligante asfáltico de base no grau de modificação provocado pela adição de PPA. Recomenda-se a adição de teores baixos de PPA para o LUBNOR (até 1%) e de teores altos de PPA para o REDUC (superiores a 1,0%). / Additives have been incorporated to asphalt binder in order to improve the performance of pavements. The stiffening of asphalt binders induced by additives should increases the rut resistance of asphalt concrete, unclear how PPA affects the resistance to fatigue and thermal cracking of asphalt binders. One of the most promising new products for asphalt binders modification is the polyphosphoric acid (PPA). However, the mechanism of PPA modification depends strongly on the chemical composition of the base asphalt binder. To evaluate the impact of the PPA modification in asphalt binders from different sources, two asphalt binders 50/70 penetration grade (REDUC and LUBNOR) from different crude source with different performance grades and chemical composition have been modified by four proportions of PPA (0.5, 1 0, 1.5, 2.0%). Saturated aromatics, resins and asphaltenes (SARA) fractions of neat and modified asphalt binders were determined using the thin-layer chromatography. To evaluate the effect of PPA addition on the rheological properties of asphalt binders it was analyzed the viscosity, the performance grade, the stiffness, the elasticity, the elastic recovery, the non-recoverable compliance and the crack length at failure. The viscosity of asphalt binders and the mixing and compaction temperature increased with increasing levels of PPA. The high temperature of PG increased in different magnitude with the ratio of PPA, depending on the base asphalt binder. The addition of PPA increases the stifiness, the elasticity and the elastic recovery and decrease the non-recoverable compliance of asphalt binders. With regard to the fatigue tolerance, the addition of PPA and the thermo-oxidative aging induced an increase in the fatigue tolerance of asphalt binders. The presented results show the importance of the chemical composition of the base asphalt binder on the extent of modification caused by the addition of PPA. It is recommended to use low levels of PPA to modify the LUBNOR (to 1%) and high levels of PPA to modify the REDUC (over 1.0%).

Pesquisas sobre aplicação de borracha de pneus descartados em pavimentação asfáltica vêm sendo desenvolvidas desde a década de 1960, especialmente nos Estados Unidos e, desde o início da década de 1990, no Brasil, como alternativa para diminuição dos problemas ambientais gerados por estes resíduos sólidos. Esta pesquisa tem por objetivo avaliar o desempenho de três misturas asfálticas do tipo concreto asfáltico usinado à quente: duas empregando teores diferentes de borracha moída e óleo de xisto (CAP 40 + 12% de borracha + 10% de óleo de xisto e CAP 40 + 20% de borracha + 15% de óleo de xisto) e uma convencional. Este estudo faz parte de um programa de pesquisa coordenado pela Escola de Engenharia de São Carlos da Universidade de São Paulo (EESC-USP), Universidade Estadual de Maringá (UEM) e Petrobrás, envolvendo a execução de misturas com borracha e óleo de xisto em trechos experimentais. Foram realizadas dosagens Marshall e ensaios de resistência à tração, módulo de resiliência e fluência por compressão uniaxial estática. Os corpos-de-prova empregados nos ensaios foram moldados no teor ótimo de cimento asfáltico referente a cada uma das misturas. Constatou-se a viabilidade técnica da adição de óleo extensor para a incorporação de borracha de pneus descartados em concreto asfáltico, permitindo a obtenção de resultados satisfatórios quanto aos projetos de dosagem das misturas pelo método Marshall. Com base nos resultados dos ensaios realizados, acredita-se ser viável a execução de trechos experimentais empregando as duas misturas modificadas. / Researches on the application of discarded tires in asphaltic pavements has been developed since 1960, mainly in the United States and since the beginning of the 90\'s in Brazil, as an alternative to the reduction of environmental problems created by this kind of solid residues. The purpose of this research is to evaluate the performance of three hot mix asphalt concrete: two using different crumb rubber and shale oil contents (CAP 40 + 12% rubber + 10% shale oil and CAP 40 + 20% rubber + 15% shale oil) and a conventional hot mix asphalt concrete. The research is part of a major program coordinated by the Universidade de São Paulo (EESC-USP), Universidade Estadual de Maringá and Petrobras, comprehending the execution of asphaltic mixtures using tire rubber and shale oil in experimental road segments. The tests performed are: Marshall test, indirect tension, resilient modulus and static creep. The samples tested were compacted in the optimum binder content of each mixture. Good results obtained in tests confirrned the technical viability of using the shale oil as extender in crumb rubber asphalt hot mixtures. The results lead to the conclusion that experimental road sections or segments may be constructed with both tested rubber-oil modified asphalt mixtures.

Das Influenza A Virus (IAV) stellt weltweit eine ernstzunehmende Bedrohung für Gesundheit und Wirtschaft der Menschheit dar. Ein universeller und langanhaltender Impfstoff konnte noch nicht entwickelt werden und klinisch zugelassene Medikamente verlieren durch die rasante Entstehung von resistenten Stämmen zunehmend ihre Wirkung. Aus diesem Grund gewinnt die Erforschung neuer antiviraler Strategien zur Bekämpfung des Influenzavirus an Bedeutung zum Schutze unserer Gesellschaft. Eine vielversprechende Zielstruktur für die Entwicklung neuer antiviraler Medikamente stellt das virale Hämagglutinin (HA) dar. Das HA liegt in hoher Dichte auf Influenzaviren vor und ermöglicht die Bindung an Sialinsäuren (SA) auf Wirtszellen und die Verschmelzung mit deren Lipidmembran. HA-bindende Moleküle entfalten eine hemmende Wirkung bereits bei dem ersten Kontakt mit Zellen, sodass eine Infektion erst gar nicht stattfinden kann. Aufgrund einer hohen HA-Dichte auf der Virusoberfläche eignen sich besonders multivalente SA tragende Nanopartikel für die Hemmung einer viralen Infektion. Aufbauend auf diesen Erkenntnissen, wurden in der vorliegenden Arbeit neue multivalente Binder gegenüber dem viralen Hämagglutinin (HA) entwickelt und studiert. Im Gegensatz zu bereits bekannten multivalenten Sialosiden, die in einer undefinierten räumlichen Orientierung auf Polymergerüsten präsentiert wurden, konnten in der vorliegenden Arbeit strukturelle Aspekte identifiziert werden, um Gerüstsysteme mit optimaler Rezeptorpräsentation gegenüber der Influenza A Virusoberfläche zu generieren. Neben SA-basierten Polymersystemen wurde auch ein gegen HA gerichtetes Peptid aus einem Antikörper identifiziert, welches sich auch für eine multivalente Interaktion mit IAV eignet. Diese Arbeit ermöglicht neue Einblicke in die Auswahl geeigneter Trägersysteme, eines optimalen Rezeptorabstandes und der Verwendung alternativer Rezeptoren mit dem Ziel einer Infektionshemmung von IAV. / Influenza A virus (IAV) still poses a serious threat to global health and economy of mankind. So far, a universal, long-lasting vaccine could not be developed, and clinically approved drugs are prone to lose activity due to the fast development of resistant strains. Because of this, research on new antiviral compounds and strategies to combat influenza viruses is of great importance for the protection of our society. A promising candidate for the development of novel antiviral drugs is the viral hemagglutinin (HA) protein. HA is present at high density on the viral envelope, which allows binding to sialic acid (SA) molecules on host cells and fusion with their membrane. Following, HA binding molecules have an inhibitory effect at the very first step of the infection cycle, leading to the inability of an infection. Based on a high HA density on the viral surface, SA carrying nanoparticles qualify for the inhibition of a viral infection. Based on this knowledge the study at hand demonstrates the development of new multivalent binders against viral HA and discusses them critically. In contrast to published multivalent sialosides, which are displayed in an undefined fashion on polymer scaffolds, the results of this thesis support the identification of structural requirements for the design of new scaffold systems with an optimal match to the viral surface. Beside sialoside based polymer systems, completely new peptide based systems, based on an HA binding antibody, were developed. Similar to polyglycerolsialosides, such multivalent peptide-decorated polymers were able to achieve nanomolar binding inhibition constants, too. In summary, this thesis enables new insights into the choice of a suitable carrier system, the optimal receptor spacing, and the use of alternative receptors with the ultimate goal of virus neutralization.

Micro RNA sind nicht-kodierende dsRNA ~22 Nukleotiden lang, die eine wichtige Rolle in der Entwicklung und Regulation in beinahe allen Eukaryoten spielen. MiRNAs binden target mRNA, was zu einer Blockierung der Proteintranslation führt. Viele Krankheiten sind bekannt, die durch veränderte miRNA Expressionsmuster entweder beeinflusst oder verursacht werden. Demnach könnte eine Manipulation der miRNA-Bildung einen therapeutischen Ansatz darstellen. MiRNA werden im Zytoplasma von längeren haarnadelförmigen prekursor RNA (pre-miRNA) durch das Enzym Dicer freigsetzt. Inhibition dieser Spaltung könnte durch spezifische pre-miRNA-bindende Moleküle erfolgen. Selektive Binder der pre-miRNA als Inhibitoren der miRNA-Reifung können durch testen von Substanzbibliotheken mit Hochdurchsatzscreening (HTS) gefunden werden. Diese Arbeit beschreibt den ersten homogenen Assay der miRNA-Reifung. Eine Fluoreszenzsonde in Form einer pre-miRNA wurde benutzt, die einen 5´-Fluorophor (FAM, Cy3, oder TMR) und einen 3´-Quencher (DABCYL) aufweist. Durch die nahe Nachbarschaft von Fluorophor und Quencher in der nativen Haarnadelstruktur erfolgt Fluoreszenzlöschung. Dicer spaltet diese Struktur effizient, was zur Dissoziation von Fluorophor und Quencher und somit zu einem Fluoreszenzanstieg führt. Der Assay wurde für HTS optimiert. Die ersten Verbindungen wurden auf deren Inhibition der miRNA-Reifung getestet. Mit einem Duplexassay, wobei zwei unterschiedliche pre-miRNA Sonden mit verschiedenen Fluorophoren eingesetzt wurden, konnte etwas spezifische Inhibition gezeigt werden. Der Assay wurde in Zellen durchgeführt und der Fluoreszenzanstieg mit Fluoreszenzmikroskopie detektiert. Somit ist ein Zell-basiertes Screening von Inhibitoren möglich. Eine einfachere Synthese der Sonde mittels in vitro Transkription und anschließender enzymatischen Ligation wurde entwickelt. Verwendung des Assays um hoch selective Inhibitoren der miRNA-Reifung zu entdecken könnte zu therapeutischen Ansätzen führen. / Micro RNAs (miRNAs) are non-coding dsRNAs of ~22 nucleotides that play a vital role in development and regulation in nearly all eukaryotes. MiRNAs bind target mRNA, thus blocking protein translation. Many diseases have been found to be influenced or caused by aberrant expression of miRNAs. A manipulation of miRNA formation may have therapeutic potential. MiRNAs are cleaved from longer hairpin precursor RNA (pre-miRNA) in the cytoplasm by the enzyme Dicer. It might be possible to inhibit this cleavage through specific pre-miRNA binding molecules. Selective binders of pre-miRNA as inhibitors of miRNA maturation can be found by testing large libraries of substances through high throughput screening (HTS) using an appropriate assay. This work describes the first homogenous assay of miRNA maturation. A fluorescent probe in the form of a pre-miRNA containing a 5´-fluorophore (FAM, Cy3, or TMR) and a 3´-quencher (DABCYL) was used. This ‘beacon’ in its native hairpin formation brings the fluorophore and quencher moieties into close proximity, resulting in fluorescence quenching. Dicer efficiently cleaves this structure, leading to dissociation of fluorophore and quencher and thus a fluorescence increase. In the presence of an RNA ligand that blocks cleavage, a lower fluorescence increase is seen. The assay was optimized for HTS. The first compounds were tested for their inhibition of miRNA maturation. Using a duplex assay, with two different pre-miRNA probes each containing a different fluorogenic group, some specific inhibition was shown. The assay was performed in cells using fluorescence microscopy to measure the fluorescence. This would allow for a cell-based screening of inhibitors. A simpler approach of beacon synthesis using in vitro transcription followed by enzymatic ligation was also established. Use of this assay to discover highly selective inhibitors of miRNA maturation may lead to disease therapeutics.

Die hydrolysestabile C-C-Bindung von Nukleosiden, deren Nukleobase über ein aromatisches oder methylen-verbrücktes Kohlenstoffatom an Ribose oder 2-Desoxyribose gebunden ist, ermöglicht die Synthese von neuartigen Strukturen und Eigenschaften, die bei N-Nukleosiden nicht stabil oder nicht gegeben wären. In dieser Arbeit wurde die die Cuprat-vermittelte Glycosylierung und die Friedel-Crafts-Alkylierung als Methoden zur Darstellung von Desoxyribose-basierenden C-Nukleosiden weiterentwickelt. Die Cuprat-vermittelte Glycosilierung ermöglichte die Synthese von C-Nukleosiden in bis zu 93% Ausbeute, wenn Grignard-basierende Normant-Cuprate verwendet wurden. Die Verwendung Organolithium-basierender Gilman-Cuprate war ebenfalls möglich. In Gegenwart von Sauerstoff wurden O-Glycoside isoliert in über 80 % Ausbeute isoliert. Mit den C-Nukleosiden wurden modifizierte Oligonukleotide, die als potentiell verbesserte Binder an M.TaqI und E.coli Dam dienen, dargestellt. Nach ihrer Charakterisierung über Schmelzwerte und Fluoreszenzeigenschaften wurde diese an die Arbeitsgruppe von Prof. Elmar Weinhold weitergereicht und dort erfolgreich als optimierte Binder an an M.TaqI und E.coli Dam getestet. Oligonukleotide, die ein oder mehrere 1,1-Binaphthyl-Chromophore als einen neuen Typus eines torsionsflexiblen Farbstoffes enthalten, wurden untersucht. Die Einführung mehrerer aufeinander folgender Binaphthyle führte zu einer thermodynamischen Stabilisierung von Duplex-Oligonukleotiden. Die geringe Neigung Binaphthyls zur Selbstlöschung bewirkte dabei einen starken Anstieg der Fluoreszenz. / The stable C-C-bond of ncleosides, whose nucleobase is attached to the ribose or 2-deoxyribose via an aromatic or methylen-bridged carbon atom, is stable to hydrolyses. This allows the synthesis of new structures and properties, which would not be available in N-nucleosides. In this work, a cuprate-mediated glycosilation and the Friedel-Crafts-alkylation as methods for the preparation of doxyribose-based C-nucleosides were developed. The cuprate-mediated glycosilation allowed the synthesis of C-nucleosides in up to 93 % yield, when Grignard-based Normant-Cuprates were used. The use of Organolithium-based Gilman-Cuprates was also possible. In the presence of oxygen O-glycosides were isolated in over 80 % yield. With the C-nucleosides modified oligonucleotides, which serve as potentially improved binders of the DNA-methyltransferases M.TaqI und E.coli, were prepared. After their charakterisation via melting point measurements and fluorescence properties, the oligonucleotides were given to the working group of Prof. Elmar Weinhold and successfully tested as improved binders of the DNA-methyltransferases M.TaqI und E.coli. Oligonucleotides, which contain one or multiple 1,1-binaphthyles as a new type of a torsionally flexible chromophore, were charakterised. The incorporation of several successive binaphthyls led to a thermodynamical stabilisation of the duplex-oligonucleotides. The low tendency of the Binaphthyl for self-quenching caused a remarkable increase of the fluorescence.

Aditivos têm sido incorporados ao ligante asfáltico no intuito de melhorar o desempenho dos pavimentos. O enrijecimento do ligante asfáltico provocado pelos aditivos, aumenta a resistência à deformação permanente das misturas asfálticas, mas ainda não se sabe qual o efeito deles sobre a resistência à fadiga e ao trincamento térmico dos ligantes asfálticos. Um dos produtos modernos mais promissores para modificação de ligantes asfálticos é o ácido polifosfórico (PPA). No entanto, o mecanismo de modificação com PPA depende fortemente da composição química do ligante asfáltico de base. Para avaliar o impacto da adição de PPA em ligantes asfálticos de diferentes fontes, dois ligantes asfálticos 50/70 (REDUC e LUBNOR), de diferentes PGs e composição química foram modificados por quatro proporções de PPA (0,5, 1,0, 1,5, 2,0%). As frações de saturados, aromáticos, resinas e asfaltenos (SARA) dos ligantes asfálticos puros e modificados foram determinadas por meio da cromatografia de camada fina. Para avaliar o efeito da adição de PPA sobre as propriedades reológicas dos ligantes asfálticos, foram analisados a viscosidade, o grau de desempenho, a rigidez, a elasticidade, a recuperação elástica, a compliância não-recuperável e o comprimento de trinca na ruptura. A viscosidade dos ligantes asfálticos e as temperaturas de usinagem e compactação aumentaram com o aumento do teor de PPA. A temperatura alta do PG aumentou com a proporção de PPA em intensidades diferentes, dependendo do ligante asfáltico de base. A adição de PPA aumenta a rigidez, a elasticidade e a recuperação elástica e diminui a compliância não-recuperável dos ligantes asfálticos. Em termos de tolerância à fadiga, a adição de PPA e o envelhecimento provocaram um aumento na tolerância à fadiga dos ligantes asfálticos. Os resultados apresentados destacam a importância da composição química do ligante asfáltico de base no grau de modificação provocado pela adição de PPA. Recomenda-se a adição de teores baixos de PPA para o LUBNOR (até 1%) e de teores altos de PPA para o REDUC (superiores a 1,0%). / Additives have been incorporated to asphalt binder in order to improve the performance of pavements. The stiffening of asphalt binders induced by additives should increases the rut resistance of asphalt concrete, unclear how PPA affects the resistance to fatigue and thermal cracking of asphalt binders. One of the most promising new products for asphalt binders modification is the polyphosphoric acid (PPA). However, the mechanism of PPA modification depends strongly on the chemical composition of the base asphalt binder. To evaluate the impact of the PPA modification in asphalt binders from different sources, two asphalt binders 50/70 penetration grade (REDUC and LUBNOR) from different crude source with different performance grades and chemical composition have been modified by four proportions of PPA (0.5, 1 0, 1.5, 2.0%). Saturated aromatics, resins and asphaltenes (SARA) fractions of neat and modified asphalt binders were determined using the thin-layer chromatography. To evaluate the effect of PPA addition on the rheological properties of asphalt binders it was analyzed the viscosity, the performance grade, the stiffness, the elasticity, the elastic recovery, the non-recoverable compliance and the crack length at failure. The viscosity of asphalt binders and the mixing and compaction temperature increased with increasing levels of PPA. The high temperature of PG increased in different magnitude with the ratio of PPA, depending on the base asphalt binder. The addition of PPA increases the stifiness, the elasticity and the elastic recovery and decrease the non-recoverable compliance of asphalt binders. With regard to the fatigue tolerance, the addition of PPA and the thermo-oxidative aging induced an increase in the fatigue tolerance of asphalt binders. The presented results show the importance of the chemical composition of the base asphalt binder on the extent of modification caused by the addition of PPA. It is recommended to use low levels of PPA to modify the LUBNOR (to 1%) and high levels of PPA to modify the REDUC (over 1.0%).