„Kontraste für Viola solo“ entstand 2002. Das 7-8-minütige Werk komplettiert einen Zyklus von drei einsätzigen Werken für ein Streichinstrument allein. Im Unterschied zur „Sonate für Violine solo“ und dem „Allegro für Violoncello solo“ (ADU-Verlag, Aurich 2001, jetzt Merseburger-Verlag, Kassel) wurden die „Kontraste“ bislang (Stand 2020) noch nicht öffentlich aufgeführt oder bei einem Verlag veröffentlicht. Im Zeitraum 2000 bis 2005 entstanden außerdem zwei abendfüllende Oratorien ('Für Deine Ehre habe ich gekämpft, gelitten' – Stationen der Passion Jesu, Oratorium für Sprecher, Sopran, Bariton, Chor und Orchester, 2000 und 'Alles, was atmet, lobe den Herrn' - ein Schöpfungsoratorium, 2003-04). Während ich mich dort um großflächige Anlagen bemüht habe, ging es mir in „Kontraste“ um scharfe Gegensätze etwa zwischen laut und leise, hoch und tief sowie lang und kurz auf engstem Raum. Der großformale Verlauf wird dadurch unkalkulierbar. Dennoch entsteht durch die Wiederkehr von Elementen, z. B. zwei- oder dreitönigen Halbtonfolgen auf- oder abwärts, der Eindruck von Geschlossenheit. (Computer-Notensatz (SIBELIUS): August 2020)

Das Trio für Violine, Horn und Klavier – in der Besetzung von Brahms‘ Opus 40 – entstand 1988 nach Abschluss meines Kompositionsstudiums bei Ulrich Leyendecker in Hamburg. Ausgangspunkt des knapp 10-minütigen Werkes ist eine punktuelle Staccato-Musik in c-Moll. Die Pausen zwischen den Ereignissen verschwinden mehr und mehr. Verdichtungen führen zu dynamischen Höhepunkten. Ein zweites Thema in der Durdominanttonart G-Dur erinnert an die Tradition der Sonatenexposition, eine virtuose Klavierpassage an die Kadenz im Solokonzert. Die Coda hebt sich durch ihr Adagio-Tempo vom Allegro der vorausgehenden Teile des einsätzigen Werkes ab. (Matthias Drude) (Überarbeitet und Computer-Notensatz (SIBELIUS): Juli - August 2020)

Das Trio für Oboe, Klarinette und Fagott entstand kurz nach Beendigung meines Kompositionsstudiums bei Ulrich Leyendecker (Hamburg) im Jahr 1988. Wie das Bläserquintett (1986), jedoch im Unterschied zum Bläseroktett (1988) und den meisten anderen meiner kammermusikalischen Werke ist es nicht ein-, sondern zweisätzig. Die beiden Sätze Allegro und Andante stehen zueinander im Verhältnis des vermittelten Kontrastes. Die Anfänge sind extrem gegensätzlich. Das Allegro beginnt rhythmisch profiliert mit großen Intervallsprüngen, das – geringfügig kürzere - Andante eher diffus mit kleinräumiger Chromatik. Im weiteren Verlauf des Andante kommen aber auch Allegro-Abschnitte vor, durch die sich der Charakter dem Kopfsatz annähert, so wie umgekehrt der 1. Satz auch ruhigere, den Andante-Charakter vorausnehmende Partien aufweist. (Computer-Notensatz (SIBELIUS): August 2020)

Das „Duo für Flöte und Klavier“ (1989) ist das zweite Werk des damals in Hannover lebenden Komponisten Matthias Drude (geb. 1960) für diese Duobesetzung. Gegenüber der Fantasie für Flöte und Klavier (1985-86) ist es mit ca. 12 Minuten deutlich länger und extrovertierter als das Vorgängerwerk. Einem Maestoso-Thema im fortissimo, das die hohe Lage der Flöte mit der tiefen Lage des Klaviers kombiniert, steht ein zweites langsameres und intimeres Thema gegenüber, bei dem der Solist in den geöffneten Flügel hineinblasen soll. Das „Duo“ ist auch durch die Idee der „Mehrsätzigkeit in der Einsätzigkeit“ angeregt. So folgt in der Mitte des Werkes auf einen langsamen Abschnitt ein Scherzando-Abschnitt im 6/8-Takt mit fugierten Partien, der im weiteren Verlauf mit dem emphatischen Hauptthema kombiniert wird. (Computer-Notensatz: September 2020)

No description available.

No description available.

Intrinsically disordered proteins (IDPs) are an abundant class of proteins and protein regions which rapidly change between multiple structures without an equilibrium position. IDPs exist as a series of conformational ensembles of semi-stable conformations that can be adopted based on a hilly landscape of shallow free energy minima. Disordered sequences share characteristic features differentiating them from globular proteins, including low sequence complexity, low occurrence of hydrophobic residues, high polar and charged residue content, and high flexibility. IDPs are commonly involved in regulation in the cell, and frequently function as, or interact with, hub proteins in protein-protein interaction networks, making them an important class of macromolecules for understanding regulatory and other processes. Given their functional importance, these proteins are widely studied. Many analytical techniques are used, though rapid conformational sampling by IDPs makes it difficult to detect many states with NMR or other techniques. Computational approaches such as molecular dynamics are increasingly used to probe the binding and conformational sampling of these proteins, allowing for observation of factors that cannot be observed with traditional analytical methods such as NMR, such as differing conformational ensembles and the dipoles of individual residues. Here, we studied the role of electrostatic interactions in IDP protein-protein interaction using molecular dynamics simulations performed with the Drude-2019 force field (FF), a polarizable model that allows for more accurate representation of electrostatics, an important factor for highly charged systems like IDPs. For this project, a prototypical protein with disordered regions, p53, was simulated with two protein partners, the nuclear coactivator domain of the CREB binding protein (CBP), and the E3 ubiquitin-protein ligase mouse double minute 2 (MDM2). p53 is widely studied, and the p53 transactivation domain (TAD) is disordered and binds to many structurally diverse partners, making this protein domain a useful model for probing the role of electrostatic interactions formed by IDPs at protein-protein binding interfaces. We found that the Drude-2019 FF allows for simulation of the p53 TAD with Cα chemical shifts comparable to those observed with NMR, supporting that the Drude-2019 FF performs well in simulating IDPs. We observed large relative change in sidechain dipole moments when comparing the p53 TAD alone and when bound to either CBP or MDM2. We observed that aliphatic and aromatic amino acids experienced the largest relative change in sidechain dipole moments, and that there is sensitivity to binding shown in this dipole response. The largest percent changes in sidechain dipole moment were found to localize at and around the binding interface. Understanding the binding interactions of IDPs at a fundamental level, including the role of electrostatic interactions, may help with targeting IDPs or their partners for drug design. / Master of Science in Life Sciences / Many proteins adopt one main structure, and these proteins are called ordered proteins. Intrinsically disordered proteins (IDPs) are an abundant category of proteins which adopt multiple structures, and transition between these different structures is based on factors such as the environment around them, modifications, or interactions with other macromolecules. The flexible structures of IDPs allow them to bind to multiple different partners and to regulate processes in the cell. Since IDPs often regulate processes important to cell function, when these proteins are mutated, misfolded, or otherwise mis-regulated the resulting issues are associated with disease states. IDPs are widely studied with analytical techniques, but because IDPs frequently change shape it can be difficult to observe certain behaviors or certain factors with these techniques. Computational approaches, such as molecular dynamics (MD). MD is the study of molecular motion and interaction, and can allow observation of factors that would be difficult or impossible to observe otherwise, such as the varying structures of IDPs or the dipole moments of specific amino acids within the proteins. For this project we wanted to probe the role of dipole moments, which are charge-based interactions, in the binding of IDPs to protein partners, to better understand how IDPs bind to different partners. We used the p53 protein as an example of IDP binding and simulated it alone and bound to two other proteins, the CREB binding protein (CBP), and the E3 ubiquitin-protein ligase mouse double minute 2 (MDM2). We observed that our simulations were comparable to experiments done with nuclear magnetic resonance spectroscopy, which served to validate that our simulations were realistic. We observed that the dipole moments of the proteins change when simulating the proteins alone and in complex, and that the largest relative changes in dipole are observed for regions of the proteins involved in binding. Probing the role of charge-based interactions in protein-protein binding interactions for IDPs can help us to greater understand these interactions at a more fundamental level and could help with targeting IDPs or their partners for drug design or other problems.

Les recherches présentées dans ce mémoire ont été rendues possible grâce à la contribution financière du CRSNG, par à leur Programme de subventions à la découverte (SD) et leur Programme de bourses d’études supérieures du Canada au niveau de la maîtrise (BESC M); du FRQNT, par leur Programme de bourse de maîtrise (B1); et du CLS, par leur Graduate and Post-Doctoral Student Travel Support Program. / Le graphène est un nano-matériau très prometteur grâce à ses excellentes propriétés mécaniques, optiques et électriques. Toutefois, la plupart de ses applications les plus novatrices requièrent de l'altérer, mais la compréhension du graphène altéré est encore limitée. Certaines applications envisagées sont en optique infrarouge. Or, notre compréhension actuelle du graphène ne permet pas d’expliquer l’apparition des pics infrarouges qui sont observés dans les bicouches et dans les monocouches fonctionnalisées. Le comportement du graphène fonctionnalisé est particulièrement contre-intuitif, puisque l’ajout de greffons le rend plus transparent, et non pas plus opaque! Un modèle proposé par Bruno Rousseau, un étudiant post-doctorant du professeur Michel Côté à l'Université de Montréal, suggère une explication à ce phénomène: bien que les phonons du graphène ne puissent pas coupler directement avec la lumière, ils coupleraient indirectement avec celle-ci grâce à des collisions sur les électrons, qui eux, peuvent coupler avec les photons. Ce couplage indirect peut produire des interférences parfois constructives, parfois destructives, de telle sorte que ce mécanisme peut autant produire des pics d’absorbance que de transparence. Dans le cadre de ce mémoire, nous avons entrepris de vérifier expérimentalement la validité de ce modèle, et nous concluons qu’il semble prédire adéquatement le comportement de l’activité infrarouge des bicouches de graphène et des monocouches fonctionnalisées. Nous avons aussi étudié les méthodes par lesquelles nous synthétisions ces différents types de graphène afin de les optimiser. Enfin, nous avons déterminé des techniques, basées sur la spectroscopie Raman, permettant de bien caractériser l’intensité de l’altération causée par ces méthodes. / Graphene is a promising nanomaterials thanks to its excellent mechanical, optical and electrical properties. However, its most innovative applications require that it be altered, but the understanding altered graphene is still limited. Some applications are considered in infrared optics. However, our current understanding of graphene does not explain the appearance of the infrared peaks that are observed in bilayers and grafted monolayers. The behaviour of grafted graphene is especially baffling, since the addition of grafts makes it more transparent, not less! A model proposed by Bruno Rousseau, a postdoctoral student of Professor Michel Côté at Université de Montréal, suggests an explanation for this phenomenon: although the phonons of graphene cannot couple directly with light, they could couple indirectly through collisions with the electrons, which can couple with photons. This indirect coupling may produce constructive and destructive interference, depending on the conditions, so this mechanism can produce absorbance peaks as much as transparency peaks. In this master’s thesis, we have undertaken to experimentally verify the validity of this model, and we conclude that it seems to adequately predict the behaviour of the infrared activity of graphene bilayers and grafted monolayers. We also studied the methods by which we synthesized these different types of graphene to optimize them. Finally, we determined techniques based on Raman spectroscopy to characterize the intensity of the alteration induced by these methods.

La matière dense et tiède (WDM) est un régime caractérisé par une densité proche du solide pour une température avoisinant celle de Fermi. Pour étudier cet état de la matière, dans cette thèse, une expérience d'interférométrie dans le domaine des fréquences est mise en place afin de mesurer la phase et la réflectivité - dans les deux directions de polarisation S et P - d'une onde sonde en réflexion sur un échantillon chauffé de manière très brève par une impulsion laser ultra-courte (sub-100fs). Il est alors porté dans un état hors-équilibre. Une méthode basée sur les mesures de réflectivité est mise en place pour contrôler la forme de l'interface entre le vide et la matière chauffée. Pour des fluences laser de l'ordre de 1 J/cm2, l'hydrodynamique d'un échantillon chauffé est étudiée par la mesure du déplacement de la surface et comparée au code hydrodynamique à deux températures ESTHER. Ensuite, la fonction diélectrique à 800 nm et 400 nm est déduite des mesures expérimentales et certaines quantités en sont extraites comme la densité électronique, la température électronique et les fréquences de collision en régime WDM. Elles sont par la suite comparées avec des modèles couramment utilisés. / The Warm Dense Matter (WDM) regime is characterised by a density close to the solid density and an electron temperature close to the Fermi temperature. In this work, the nonequilibrium Warm Dense Matter is studied during the solid to liquid phase transition induced by an ultra short laser interacting with a solid. A 30 femtoseconds time resolution pump-probe experiment (FDI) is set up, yielding to the measurement of the heated sample complex reflectivity for both S and P polarisation.We have determined a criterion based on the measured reflectivities, which permits to control the interface shape of the probed matter. For pump laser fluences around 1 J/cm2, the hydrodynamics of the heated matter is studied and experimental results are compared to the two-temperatures code ESTHER. Furthermore, the evolution of the dielectric function at 800 nm and 400 nm is inferred from our measurements on a sub-picosecond time-scale. Within the Drude-Lorentz model for the conduction electrons, the dielectric function yields information such as ionisation state, electronic temperature and electron collision frequency.

O Brasil possui uma rica diversidade em espécies de plantas nativas cujo potencial bioativo, embora ainda pouco investigado, as coloca como alvos de pesquisa na área de produtos naturais. Dentre as espécies nativas estão o açaí-do-Pará (Euterpe oleraceae Mart.) e o inajá (Maximiliana maripa Aubl. Drude), frutos processados visando, principalmente, a obtenção de polpa e óleo. Contudo, a extração mecânica do óleo por prensagem gera grande quantidade de um material residual denominado \"torta\", geralmente descartado no meio ambiente como resíduo ou destinado à alimentação animal. Considerando-se a busca por ingredientes ativos naturais em substituição aos sintéticos para aplicação industrial, e a necessidade de exploração científica de resíduos agroindustriais, este trabalho teve como objetivo otimizar a extração de compostos antioxidantes de tortas de açaí e inajá, e avaliar a composição fenólica dos extratos otimizados pela técnica de espectrometria de massas de alta resolução (LC-ESI-QTOF-MS), bem como suas atividades biológicas antioxidante, citotóxica e anti-inflamatória (in vitro) e antimicrobiana. Para tanto, a melhor condição de extração dos compostos antioxidantes foi determinada empregando-se um planejamento experimental com delineamento do tipo DCCR juntamente com a metodologia de superfície de resposta. A atividade antioxidante (variável resposta) foi determinada pelos métodos de sequestro do radical ABTS, FRAP e redução do reagente Folin-Ciocalteau, sob diferentes temperaturas de extração e concentrações de etanol (variáveis exploratórias). Encontrada a condição de extração ideal (70°C e 50% de etanol, v/v) foi realizada a caracterização fenólica por espectrometria de massas de alta resolução, que possibilitou a identificação de 20 compostos bioativos no extrato de torta de açaí e de 6 no de inajá, dentre os quais estão apigeninas, catequinas e derivados do ácido caféico. As atividades biológicas avaliadas foram: antioxidante, determinada pelos métodos de sequestro dos radicais livres sintéticos ABTS e DPPH, FRAP, redução do reagente Folin-Ciocalteau, além da desativação de espécies reativas de oxigênio (radical peroxila, ânion superóxido e ácido hipocloroso); anti-inflamatória, pela inibição da ativação do fator de transcrição NF-κB; e antimicrobiana, pela determinação da CIM e CBM. Os resultados indicaram que ambos os extratos apresentaram elevada atividade antioxidante, todavia, o extrato de torta de açaí destacou-se em comparação ao da torta de inajá. O extrato da torta de açaí não promoveu redução da viabilidade celular para a cultura de macrófagos RAW 264.7 nas concentrações de 1, 10 e 100 μg/mL, enquanto que no extrato de torta de inajá não foi verificada redução da viabilidade nas concentrações de 1, 10, 100 e 1000 μg/mL (p>0,05). Os extratos ainda apresentaram atividade anti-inflamatória, sendo os extratos das tortas de inajá e de açaí capazes de inibir a ativação de NF- κB em 40 e 100%, repectivamente. O extrato de torta de inajá não apresentou atividade antimicrobiana, ao passo que o de torta de açaí inibiu o crescimento de bactérias patogênicas em concentrações de 1250 e 2500 μg/mL. Este trabalho mostra o potencial bioativo desses resíduos, corroborando com potenciais aplicações tecnológicas de seus extratos em escala industrial. / Brazil has a rich diversity of native plant species which bioactive potential, although still unexploited, places them as research targets in the natural products area. Among these native species are açaí-do-Pará (Euterpe oleraceae Mart.) and inajá (Maximiliana maripa Aubl. Drude), fruits processed mainly aiming the extraction of pulp and oil. However, the oil mechanical extraction by pressing results in great amounts of a residual material termed \"cake\", generally discarded in the environment or destined to animal feeding. Considering the search for natural active ingredients to substitute the synthetic ones for industrial application, and the need of scientific investigation of agroidustrial residues, this paper aimed to optimaze the extraction of antioxidant compounds from açaí and inajá cakes, and to evaluate the phenolic composition of the extracts by high resolution mass spectrometry (LC-ESI-QTOF-MS), as well as their antioxidant, cytotoxic and anti-inflammatory (in vitro), and antimicrobial, activities. For this purpose, the best condition for extraction of the antioxidante compounds was determined by using an experimental design with a RCCD design together the response surface methodology. The antioxidant activity (dependent variable) was determined by the methods ABTS radical scavenging, FRAP assay and Folin-Ciocalteau reagent reduction, under different temperatures (°C) of extraction and ethanol concentrations (%, v/v) (independent variables). Established the best extraction condition (70°C and etanol 50%, v/v), the phenolic profile of the cakes extracts was characterized by LC-ESI-QTOF-MS, which made possible the identification of 20 bioactive compounds in açaí cake extract and 6 in inajá cake extract, among which are apigenins, catechins and caffeic acid derivatives. The following biological activities were analyzed: antioxidant, by ABTS and DPPH synthetic radicals scavenging assay, FRAP, Folin-Ciocalteau reagent reduction, and oxygen reactive species deactivation (peroxil, superoxide and hipochlorous acid radicals); anti-inflammatory, by the inhibition of the transcription factor NF-κB activation; and antimicrobial, by determining MIC and MBC. The results indicated that both extracts show high antioxidante activity, however, the açaí cake extract stood out compared to inajá cake extract. The açaí cake extract didn\'t decrease cell viability for RAW 264.7 macrophages culture in the concentrations 1, 10 and 100 μg/mL, while the inajá cake extract didn\'t decrease the cell viability in the concentrations 1, 10, 100 and 1000 μg/mL (p>0,05). The extracts still exhibited anti-inflammatory activity, being the inajá and açaí cakes extracts capable to inhibit NF-κB activation in 40% and 100%, respectively. The inajá cake extract didn\'t show antimicrobial activity, while açaí cake extract inhibited the growing of pathogenic bacteria in concentrations of 1250 and 2500 μg/mL. This work confirms the bioactive potential of the residues, supporting possible technological applications of the extracts on an industrial scale.