No description available.

Halphen's Theorem states that, "A necessary and sufficient condition for every dynamical trajectory in a positional field of force in E3 to be planar is that the field of force is either parallel or central." This result has been known for some time, however only the sufficiency part of the theorem is widely documented. A new analytic proof of the necessity part of Halphen's Theorem was developed. The details of this proof motivated the new concepts of a flat point in a field of force and a flat point on a dynamical trajectory in a positional field of force. / Ph. D.

A significant focus of nucleic acids research is on the reactivity of electrophilic species with DNA to form addition products (adducts). Phenols are known to be able to form adducts at the C8 site of deoxyguanosine (dG). This dissertation studies the oxygen (O)-linked class of phenolic dG adducts for their hydrolytic stability as well as their structural impact on the DNA duplex. To determine the effect of C8 O-linked phenolic dG adducts on glycosidic bond stability spectrophotometric determination of hydrolysis kinetics was performed. The kinetics establish the adducts to be less stable than native dG in acid, but surprisingly stable under physiological conditions. Then to assess the modified duplex structure, a C8 O-linked phenolic dG adduct was incorporated into a DNA duplex. Thermal melting analysis establish the adduct as having a destabilizing effect on the regularly paired duplex and the conformational analysis suggests the phenolic lesion to be weakly mutagenic. / NSERC

Association rule mining is one of the most popular data mining methods. However, mining association rules often results in a very large number of found rules, leaving the analyst with the task to go through all the rules and discover interesting ones. Sifting manually through large sets of rules is time consuming and strenuous. Although visualization has a long history of making large amounts of data better accessible using techniques like selecting and zooming, most association rule visualization techniques are still falling short when it comes to large numbers of rules. In this paper we introduce a new interactive visualization method, the grouped matrix representation, which allows to intuitively explore and interpret highly complex scenarios. We demonstrate how the method can be used to analyze large sets of association rules using the R software for statistical computing, and provide examples from the implementation in the R-package arulesViz. (authors' abstract)

For over twenty years, flower-visitation networks have been used to assess the effects of pollinator decline, linked to habitat loss, climate change and invasive species, on entire communities. However, most rely on flower visit frequency as a proxy for pollination; very few sample pollen from flower visitor's bodies or from stigmas and so do not include a quantitative measure of pollination success. Here, I add pollinator effectiveness (as single visit pollen deposition) into a traditional flower visitation network, creating a pollinator importance network that better evaluates the flower visitor community from the plant's perspective. Given recent interest in pollination in urban areas, I use an urban garden habitat, and compare visitation, pollen transport and pollinator importance networks, giving several novel conclusions. Firstly, although there are similarities in the structure of my networks, interactions were most specialised in the pollinator importance network, with pollen transport proving to be a better proxy for pollinator importance than visitation alone. Secondly, the specialisation of individual plants and the role of individual flower visitors varied between the networks, suggesting that community-level patterns in simple visitation networks can mask important individual differences. Thirdly, the correlation between flower visit frequency and pollinator importance largely depends on bees, and may not hold in plant-pollinator communities that are not bee-dominated. Fourthly, heterospecific pollen deposition was relatively low, despite the unusually diverse plant community of a garden. Finally, bees (particularly Bombus and non-eusocial halictids) carried the largest pollen loads and were the most effective at depositing pollen on to the stigma during a single visit in this garden habitat. The implications of this thesis highlight the strengths and limitations of each network for future studies, and raise important questions for the future of urban pollination studies.

This thesis is a fundamental reassessment of Jacobean crown finance and its importance in the early-modern English polity. The concurrent focuses are the Jacobean conceptualization of crown finance in terms of projects and the analysis of fiscal policy. Fiscal policy was dominated by attempts to balance the consumptive demands of the patronage culture with the fiscal needs of meeting the state's responsibilities of governance. The introduction describes the origins of projects and their relationship to the Jacobean patronage culture; it also discusses the importance of fiscal policy as a jumping-off point for a reassessment of the Jacobean polity. The structures of policymaking are examined in Chapter 1 with special emphasis on the process of counsel and the central role of James I in the responsibilities of governance. The conceptualization of crown finance in terms of entrepreneurial-like projects is fully explored in chapter 2 as is the importance of the doctrine of necessity in fiscal policy. Chapter 3 examines the nature of projects using a case-study of fishing fleet initiatives. The most significant challenge to the project basis of finance occurred in the parliament of 1621; the consequences of these events, long misunderstood as an attack on monopolies, are re-examined in Chapter 4. Origins of opposition to projects in popular culture, among James' ministers, and in parliament preface this chapter. The three chapters making up section II of the thesis seek to rehabilitate fiscal policy with a focus on policymaking and governance. Robert Cecil's project for fiscal refoundation would have established a precedent of public taxation to support the crown. Its collapse is subjected to a reinterpretation in Chapter 5 which challenges Revisionist orthodoxy on Jacobean parliamentary politics and political philosophy. Chapter 6 examines a number of attempts through conciliar policymaking (1611-1617) to meet ongoing financial challenges which ultimately influenced fiscal policy for the rest of James' reign. The concluding chapter recreates Lionel Cranfield's formulation and application of the abstract ideal of the public good in fiscal policy. Cranfield represents the sharpest Jacobean example of a minister seeking to balance the demands of serving the king and the state in their own rights; and the challenges of so doing. The conclusion places the thesis into a wider perspective of early- modern governance and our understanding of the Jacobean polity.

Ce travail décrit la synthèse et l’étude conformationnelle de nouveaux oligomères mixtes. Dans le premier chapitre, en exploitant des travaux antérieurs concernant la synthèse des N-aminodipeptides, nous avons obtenu des oligomères mixtes, alternant des liens amides et N-aminoamides nommés [[allpha]/[alpha]-N-amino]mères. L’oligomérisation des N-aminopeptides en phase liquide est réalisable grâce à un couplage au fluorure d’acide à partir d’une unité de base possédant les protections Boc (extrémité N-terminale), Bn (extrémité C-terminale) et phtaloyle (azote latéral). Le deuxième chapitre présente les résultats obtenus par différentes méthodes spectroscopiques (RMN, IR et DC) et modélisation moléculaire sur les différents oligomères synthétisés dans le chapitre 1. Ces travaux ont permis de mettre en évidence un repliement répétitif original par une liaison hydrogène de type C8 impliquant un groupement carbonyle du phtalimide et un proton amidique / This work describes the synthesis and the conformational study of new mixed oligomers. In the first chapter, using previous work on the synthesis of N-aminodipeptids, we were obtained mixed oligomers alternating amid and N-aminoamid bond named [[alpha]/[alpha]-N-amino]mers. The oligomerization of N-aminopeptids in liquid phase was achieved through an acid fluorid coupling from a building block with the protections Boc (N-terminus), Bn (C-terminus) and phtaloyl (N-side). The second chapter presents the results obtained by different conformational spectroscopic methods (NMR, IR and DC) and molecular modeling on the various oligomers synthesized in Chapter 1. This work has allowed to highlight a original repetitive folding by a C8 hydrogen bond involving the carbonyl group of phthalimid and a amid proton

In dieser Arbeit werden neue Strategien zur Wachstumskontrolle funktionaler organischer Dünnschichtmaterialien aufgezeigt, mit denen sich die Eigenschaften molekularer Schichtsysteme gezielt beeinflussen lassen. Ein Fokus liegt dabei auf der Untersuchung des Einflusses von optischen Feldern auf das Wachstumsverhalten. Ein weiterer Schwerpunkt wird auf das Grundlagenverständnis von thermisch aktivierten, kinetischen Prozessen, die die Morphologie während und nach dem Schichtwachstum beeinflussen, gelegt. Zuerst wird am Beispiel des molekularen Halbleiters Sexithiophen (6T) gezeigt, wie sich Kontrolle über das Kristallphasengleichgewicht während des Wachstums auf Kaliumchlorid (KCl) erzielen lässt. Im zweiten Teil der Arbeit wird eine neue Herangehensweise zur direkten Ausrichtung von Molekülkristallen im optischen Feld während ihrer Entstehung studiert. Am Beispiel von Tetracene wird gezeigt wie sich so optische anisotrope Absorptionseigenschaften von Molekülen dazu nutzen lassen den Brechungsindex eines polykristallinen Films lokal durch ein photolitographisches Verfahren zu beeinflussen. Im dritten Teil wird der Einfluss von dynamisch variierenden Wachstumsbedingungen während des Schichtwachstums von PTCDI-C8 studiert. Es wird gezeigt, dass sich die Oberflächenrauigkeit stark reduzieren lässt, indem zu Beginn des Wachstums jeder individuellen molekularen Monolage die Nukleationsdichte stark erhöht und in den darauf folgenden Wachstumsphasen die Diffusivität gezielt gesteigert wird. Im vierten Teil wird das Diffusionsverhalten von n-Alkan Schichten unter thermischen Einflüssen betrachtet. Es wird gezeigt, dass die inhärente molekulare Anisotropie von C44H90 Molekülen (TTC) sowie die sehr geringe, stark anisotrope, Oberflächenenergie dieses Materials ein ungewöhnliches Diffusionsverhalten auslöst. / The research performed in the framework of this thesis focuses on new strategies to effectively control the growth of crystalline thin films of functional organic molecules and attributes the quest for additional growth control parameters in organic molecular beam deposition (OMBD). First the influence of light on the growth process of the sexithiophene (6T) is studied. We find that 6T thin films deposited as conventional in dark environments on KCl exhibit a bimodal growth with phase coexistence of two crystal polymorphs. In contrast, films grown under illumination with 532 nm light show increased phase purity. Further, we establish light-directed molecular self-assembly (LDSA) to generate permanently aligned thin films of tetracene (C18H12) and demonstrate direct patterning with light. Polarized light illumination leads to azimuthally photoaligned films on isotropic, amorphous substrates. Thus, LDSA can be regarded as a new degree of freedom in the quest for control-parameters in organic thin film growth. Next the impact of dynamic temperature oscillations on the time scales of molecular monolayer growth during organic molecular beam deposition is discussed. We strongly increase the island density during nucleation and selectively increase interlayer diffusion at later stages of monolayer growth. We analyse the interplay between molecular interlayer transport and island sizes to understand kinetic processes during growth. In a fourth experiment we show how thermal annealing can be used to improve smoothness and to increase the lateral size of crystalline islands of n-alkane (TTC, C44H90) films. We employ real-time optical phase contrast microscopy to track the diffusion across monomolecular step edges which causes the unusual smoothing during annealing. We rationalise the smoothing behaviour with the highly anisotropic attachment energies and low surface energies of TTC.

No description available.

Les maladies neurodégénératives liées à l’âge, telle celle de Parkinson, sont un problème majeur de santé publique. Cependant, la maladie de Parkinson reste incurable et les traitements sont très limités. En effet, les causes de la maladie restent encore mal comprises et la recherche se concentre sur ses mécanismes moléculaires. Dans cette étude, nous nous sommes intéressés à deux phénomènes anormaux se produisant dans la maladie de Parkinson : l’agrégation de l’α-synucléine et l’activation des cellules microgliales. Pour étudier la polymérisation de l’α-synucléine, nous avons établi de nouvelles méthodes permettant la production in vitro de différents types d’oligomères d’α-synucléine. Grâce à des méthodes biophysiques de pointe, nous avons caractérisé ces différents oligomères à l’échelle moléculaire. Puis nous avons étudié leurs effets toxiques sur les neurones. Ensuite, nous nous sommes intéressés à l’activation des microglies et en particulier à leurs canaux potassiques et aux changements liés au vieillissement. Nous avons identifié les canaux Kv1.3 et Kir2.1 et montré qu’ils étaient impliqués dans l’activation des microglies. En parallèle, nous avons établi une méthode originale qui permet l’isolation et la culture de microglies primaires issues de cerveaux adultes. En comparaison à celles de nouveaux-nés, les microglies adultes montrent des différences subtiles mais cruciales qui soutiennent l’hypothèse de changements liés au vieillissement. Globalement, nos résultats suggèrent qu’il est possible de développer de nouvelles approches thérapeutiques contre la maladie de Parkinson en modulant l’action des microglies ou en bloquant l’oligomérisation de l’ α-synucléine. / Age-related neurodegenerative disorders like Parkinson’s disease take an enormous toll on individuals and on society. Despite extensive efforts, Parkinson’s disease remains incurable and only very limited treatments exist. Indeed, Parkinson’s pathogenesis is still not clear and research on its molecular mechanisms is ongoing. In this study, we focused our interest on two abnormal events occurring in Parkinson’s patients, namely α-synuclein aggregation and microglial activation. We first investigated α-synuclein and its abnormal polymerisation. For this purpose, we developed novel methods, which allowed the in vitro production of different types of α-synuclein oligomers. Using highly sensitive biophysical methods, we characterised these different oligomers at a single-particle level. Then, we tested their biological effects on neurons. Afterwards, we studied microglial activation. We concentrated our efforts on two axes, namely age-related changes in microglial function and K+ channels in microglia. We showed that Kv1.3 and Kir2.1 K+ channels are involved in microglial activation. In parallel, we developed a new approach, which allows the effective isolation and culture of primary microglia from adult mouse brains. Adult primary microglia presented subtle but crucial differences in comparison to microglia from neo-natal mice, confirming the hypothesis of age-related changes of microglia. Taken together, our results support the hypotheses that microglial modulation or inhibition of α-synuclein oligomerisation are possible therapeutic strategies against Parkinson's disease.