This thesis explores the importance of the United Kingdom’s composition as a multinational state to the decoration of the new Houses of Parliament, constructed by Sir Charles Barry following the destruction of most of the old Palace of Westminster by fire in 1834. Over seven chapters, it examines the decorative schemes undertaken between the 1840s and 1860s by Barry and the Fine Arts Commission, followed by later, individual programmes, the last of which was completed in 1928. This study develops the twin notions of the art of union and the art of disunion to analyse the complex relationship between the Union and Parliament’s decorative schemes. The art of union is used to identify the elements of the New Palace of Westminster’s planned or completed decoration that validated and promoted the Union. Meanwhile, the art of disunion is deployed as a means of analysing the works of art that caused disunity and division. Examples of the art of union in the Houses of Parliament have led to it being described as a very British building. However, this thesis argues that this is an inadequate description. Though Scotland, Ireland and Wales are represented in the building’s decoration, it is England that dominates. Therefore, this study argues that Anglo-British is the most accurate term with which to describe the sense of national identity embodied by the Palace of Westminster. However, the Anglo-Britishness presented over the lengthy period covered in this thesis is not a consistent and homogenous vision, but one that is varied, complex and, at times, contradictory. There is also a clear development in the general form that it takes: beginning with a relatively inclusive Anglo-Britishness that gives some recognition to the UK nations other than England, it becomes increasingly Anglocentric and imperialist over the period examined.

Approved for public release, distribution is unlimited / There is a growing movement throughout the Department of Defense (DoD) towards the implementation of Network Centric Warfare (NCW). In an effort to transition to NCW, the Navy has fielded many different technologies. One system exploiting new technologies in the Intelligence, Surveillance, and Reconnaissance (ISR) domain is the Joint Fires Network/Tactical Exploitation System-Navy (JFN/TES-N), which was developed from the Army Tactical Exploitation System, (TES-A). This system was developed rapidly and uniquely for fleet deployment in accordance with the interim acquisition guidance signed by the Honorable Paul Wolfowitz. This guidance authorized Evolutionary Acquisition following a Spiral Development process in lieu of the "traditional" cold war process described in the DoD 5000 series publications. Assuming that (JFN/TES-N) will be viewed as a successful acquisition, several Navy personnel have stated that it may become the model for future C4I (and other) system acquisitions. This thesis seeks to help develop that model. The objectives of this thesis are: ʺ To examine whether the TES-N acquisition process is an appropriate model of Evolutionary Acquisition following a Spiral Development. ʺ To identify and make recommendations for changes or improvements to the TES-N acquisition program, so it can be used as a more appropriate model for Evolutionary Acquisition following a Spiral Development. This thesis concludes that Evolutionary Acquisition following a Spiral Development shown with the JFN/TES-N system is an acquisition policy that is appropriate for programs of the same size and scope, but larger more complex programs will not have as much success. Yet, in order for the JFN/TES-N program and future programs using Evolutionary Acquisition following a Spiral Development to succeed, changes have to be made in policies such as budgetary submissions, test and evaluation, policy, process, and training. / Ensign, United States Navy

Les travaux rapportés dans ce mémoire concernent le développement de la réactivité de N-tosylhydrazones dans la création de liaisons carbone-carbone et carbone-azote ainsi que leurs applications à la synthèse des analogues de l’isocombrétastatine A-4 (isoCA-4), aux propriétés antivasculaires.Au cours de ce travail, des molécules de type 1,1-diaryléthylène furent synthétisées par un couplage pallado-catalysé entre des N-tosylhydrazones et des aryles halogénés. Ainsi, des oléfines polysubstituées avec un motif alcoxyle, analogues de l’isoCA-4, ont présenté des activités biologiques intéressantes. De même, les N-tosylhydrazones constituent des intermédiaires pour la synthèse de 1,5-énynes aromatiques. La cyclisation de ces derniers a pu être contrôlée selon la nature du catalyseur utilisé. En effet, en présence de l’or comme catalyseur, une cyclisation 6-endo-dig majoritaire est obtenue alors qu’en présence du palladium, une cyclisation 5-exo-dig exclusive est observée. Cette méthode permettrait de synthétiser des analogues contraints de l’isoCA-4. Le couplage réducteur, catalysé au cuivre, entre des N-tosylhydrazones et des amines et conduisant à des motifs arylalkylamines fut développé. Enfin, un processus cascade entre des 2’-halogéno-biaryl- N-tosylhydrazones et des amines fournit des dérivés du fluorène par la création d’une liaison CN et d’une liaison CC sur le même atome carbénique. / This manuscript reports the development of new metal-catalyzed reactions using N-tosylhydrazones as coupling partners for the creation of carbon-carbon and carbon-nitrogen bonds. These reactions are applied in the synthesis of analogues of isocombretastatine A-4 (isoCA-4), a vascular disrupting agent.First, a palladium-catalyzed cross-coupling reaction between N-tosylhydrazones and aryl halides was developed. By this means, polysubstituted olefins with an alkoxy motif were synthesized and presented good biological activities. Then, aromatic 1,5-enynes were synthesized by a multi-step approach using N-tosylhydrazones as intermediates. The regioselectivity of the cyclisation of these enynes was controlled depending on the reaction conditions. Under gold catalysis, a major 6-endo-dig cyclisation pattern leads to naphthalene derivatives while under palladium catalysis; an exclusive 5-exo-dig cyclisation furnishes benzofulvène derivatives. Conformationnally restricted isoCA-4 analogues could be synthesized by applying this method. A copper-catalyzed reductive coupling between N-tosylhydrazones and amines leading to -branched amine derivatives was also developed. Finally, a cascade reaction between 2’-halo-biaryl-N-tosylhydrazones and amines furnished fluoren scaffold by the formation of CC and CN bonds on the same carbenic atom.

Thesis (M.F.A.)--Boston University

A mudança de uso da terra no Cerrado acarreta em alterações na dinâmica da matéria orgânica do solo (MOS). Práticas de manejo com revolvimento das camadas de solo aceleram a decomposição da MOS, favorecendo as emissões de gases do efeito estufa do solo para atmosfera. Dessa forma, o objetivo desse trabalho foi avaliar as mudanças na dinâmica da MOS de um Neossolo Quartzarênico submetido a diferentes usos e sistemas de manejo, utilizando como referência o sistema nativo (Cerrado). O presente estudo foi realizado no município de Comodoro - MT (13º50\'00\" a 13º50\'03\" S e 59º37\'18\" O). Foi empregado o delineamento experimental inteiramente casualizado com sete áreas de estudo. As coletas foram realizadas em julho de 2005 e fevereiro de 2006 e as áreas amostradas foram: Cerrado nativo (CER); pastagem (CAP22); plantio convencional com a cultura da soja (CS1), sucessão de culturas arroz-soja (CAS3) e sucessão arroz-soja-sorgo ou milheto (CAS/Sor3 e CAS/M3); e plantio direto (CAP13S/M5). Foram estudadas as seguintes variáveis: atributos físicos e químicos do solo, estoques de carbono (C) e nitrogênio (N) do solo, teores de C e N nas frações granulométricas da MOS, quantidades de N inorgânico, C e N microbiano do solo, quociente metabólico (qCO2) e fluxos de gases do solo (CO2, N2O e CH4). Os resultados deste estudo indicaram que os sistemas com plantio convencional e plantio direto avaliados apresentaram melhoria nos atributos físicos e químicos do solo em relação a pastagem (CAP22), com menor compactação do solo e aumento na disponibilidade de fósforo, cálcio e magnésio. Foram obtidos maiores estoques de C e N em CAS/Sor3 e CAS/M3, áreas com maiores teores de argila. A área CAP13S/M5 também mostrou maiores teores de argila, porém baixos estoques de C e N, resultado atribuído ao uso da terra por treze anos com pastagem sem reforma e ao pouco tempo de implantação do sistema plantio direto. Analisando as frações granulométricas da MOS verificou-se maiores teores de C e N na fração menor que 50 \'mü\'m. As maiores quantidades de N inorgânico em relação ao CER foram observados na área CAS/M3, e com exceção desta área, a forma predominante de N inorgânico foi o amônio. Foram obtidas maiores quantidades de C e N microbiano na época úmida, quando todas as áreas estavam com cobertura vegetal. Entre as áreas de estudo, as maiores quantidades de C e N microbiano foram obtidos em CAP22. Os fluxos de C-CO2, com exceção da área CAS/Sor3, foram maiores na época úmida, enquanto que os fluxos de N-N2O e C-CH4 foram semelhantes entre as épocas de estudo. Os fluxos de gases em C equivalente não apresentaram diferenças significativas entre as áreas de estudo devido ao alto desvio padrão verificado para cada gás. A mudança de uso da terra promove alterações na dinâmica da MOS, porém neste estudo não foi possível distinguir qual o melhor sistema de uso para o Neossolo Quartzarênico devido ao pouco tempo de implantação dos sistemas plantio convencional e plantio direto, e a degradação da pastagem (apesar do maior tempo de implantação) / Land-use changes of Brazilian savanna (Cerrado) result in alterations of the soil organic matter (SOM). Managements practices with tillage accelerate the SOM decomposition, enhancing greenhouse gases emissions from the soil to the atmosphere. Therefore, the objective of this work was to evaluate the changes in the SOM dynamics of a Typic Quartzipisamment submitted to different uses and managements systems, using as reference the native system (Cerrado). The present study was conducted in areas located at Comodoro (Mato Grosso state, Brazil) (from 13º50\'00\" till 13º50\'03\" S and 59º37\'18\" W). At each site, samples were taken randomly within seven areas. Sampling activities were performed in July 2005 and February 2006 and the sample sites consist of an area of \"Cerrado\" (CER); pasture (CAP22); conventional tillage with soybean (CS1), rice-soybean succession (CAS3) and rice-soybean-sorghum or millet (CAS/Sor3 and CAS/M3) successions; and a field with no-tillage system (CAP13S/M5). Studied variables were: physical and chemical attributes, C and N stocks, isotopic composition of 13C/12C and 15N/14N, C and N content in the SOM fractions, quantity of inorganic N, microbial C and N biomass, metabolic quotient (qCO2), and the soil gases fluxes (CO2, N2O and CH4). The results of this study showed that all evaluated fields under conventional or no-tillage systems result in physical and chemical attribute improvement in relation to the pasture (CAP22), with soil compaction decrease, pH increase and improvement of the availability in phosphorus, calcium and magnesium. The C and N stocks were higher in areas CAS/Sor3 and CAS/M3, corresponding to the highest clay content. The area CAP13S/M5 showed similar clay content, but smaller C and N stocks, this result was attributed to the land-use: thirteen years as pastures without reform and also the short time of no-tillage implantation. Analyzing the SOM fractions, it was verified higher C and N contents in the 50 \'mü\'m fraction. The higher quantities of inorganic N in relation to the CER were found in area CAS/M3, and with exception of this area, ammonium was the predominant form of inorganic N. Higher quantities of the microbial C and N were obtained during the wet season, when all areas presented a cover crop. Among areas, the higher quantities of microbial C and N were obtained in CAP22. The fluxes of C-CO2, excepting area CAS/Sor3, were higher during the wet season, while the fluxes of N-N2O and C-CH4 were similar between seasons studied, because high standard deviations were calculated for each gas. The land use promoted alterations in SOM dynamic, however it was not possible to differentiate the best land use for this Typic Quartzipisamment, mainly due to the short time of no-tillage implantation, and the degradation of the pasture (although of the implantation time was higher)

Im Rahmen eines vierjährigen Feldversuches wurden der Einfluss von Bodenbearbeitung, Bodenbedeckung und Stickstoffdüngung auf die N-Dynamik und N-Verlagerung während der Winterhalbjahre und deren Nachwirkungen auf die Hauptfrucht der nachfolgenden Vegetationsperiode untersucht. Es zeigte sich, dass sich neben den Prüffaktoren auch Unterschiede der Vorfrucht und des Witterungsverlaufes auf die Höhe der Nitratauswaschung über Winter auswirkten. Generell führte der Anbau von Winterrübsen gegenüber der Brache erwartungsgemäß zu einer Reduzierung des N-Austrages, was sowohl auf die geringeren Sickerwassermengen als auch auf die geringeren Nitratkonzentrationen in der Bodenlösung zurückzuführen war. Die N-Konservierung der Winterrübsen wirkte sich auf die folgende Hauptfrucht positiv hinsichtlich der Stickstoffverfügbarkeit im Oberboden und der N-Aufnahme des Sommerweizens während dessen Standzeit aus. Der Schwerpunkt in der methodischen Vorgehensweise dieser Arbeit lag in der Erfassung der Sickerwassermengen zur Abschätzung der N-Verlagerung anhand der Daten der Nitratkonzentration in der Bodenlösung. Die Durchflussmengen im Boden wurden ausgehend von der klimatischen Wasserbilanz und unter Berücksichtigung der Veränderungen der Bodenwasservorräte bestimmt, die anhand von Messungen der Matrixpotentiale und der Kenntnis der Bodenwassercharakteristika im Profilverlauf des Bodens berechnet wurden. Dieser Ansatz wurde drei weiteren Ansätzen gegenübergestellt. Diese sind die klimatische Wasserbilanz, die klimatische Wasserbilanz unter Berücksichtigung der Veränderungen der Bodenwasservorräte anhand der volumetrischen Wassergehaltsmessung mit Hilfe der TDR-Messtechnik und die Bestimmung der Perkolation mittels Wasserleitfähigkeitsfunktionen und Potentialgradienten. Mögliche Fehlerquellen der verschiedenen Ansätze wurden diskutiert und Schlussfolgerungen für die praktische Versuchsdurchführung gezogen. / The influence of different tillage managements, soil covering and different nitrogen applications on the N-dynamic and N-leaching during winter and their effects during the following vegetation period have been investigated within the scope of a field trial of several years. Beside these treatments, differences of the preceding crop type and climatic conditions showed also effects on the amount of nitrate leaching during winter. The cultivation of winter rape compared to fallow reduced the N-leaching in accordance with the expectations; generally this was the result of lower rates of water flow as well as lower nitrate concentrations in the soil solution. During the successive vegetation periods the N-conservation by the catch crop led to higher nitrate contents in the soil, particularly in the upper layer, and to an increasing N-uptake of the fallowing spring wheat. Focal point of the methodical proceeding of this study was the recording of the downward water movement to estimate the N-leaching in combination with the nitrate concentration in the soil solution. The calculation of the water movement in the soil based on the climatic water balance in consideration of the variation of the soil water content; the changes in the soil water were determined by data of the soil matrix potential and the knowledge of the moisture characteristics of the horizons, their positions and their wideness. This approach was based to present the results, and was then compared with three other ones. These were the climatic water balance, the climatic water balance in consideration of the variation of the soil water content by data of the changes of the volumetric soil water content measured by ‘time domain reflectrometry’ and the calculation of water flow with hydraulic conductivity functions and data of the hydraulic potentials. Possible sources of error of the methods are discussed to draw conclusions for conducting field trials.

O metabolismo do triptofano (TRP) se dá por três vias metabólicas: a via das quinureninas, a via serotonérgica e a via das triptaminas. A primeira gera quinurenina e uma gama de produtos secundários e contribui para os fenômenos de tolerância e imunoescape de células tumorais. A via serotonérgica leva à produção de neuromediadores e pode gerar melatonina. Há evidências de que compostos desta via podem controlar o crescimento tumoral. A via das triptaminas origina triptamina (TRY) e N-N-dimetiltriptamina (DMT) e representa a rota menos conhecida de degradação do TRP. Assim, investigamos a via das triptaminas em linhagens de melanoma humano SK-Mel-19 e SK-Mel-147. A expressão gênica das enzimas aminoácido aromático descarboxilase (DDC) e indoletilamina-N-metiltransferase (INMT), que convertem o TRP em TRY e DMT, respectivamente, foi determinada por PCR em tempo real. Os metabólitos desta via foram detectados por LC/MS no sobrenadante das culturas celulares. O teste da ferida (scratch test) e o ensaio clonogênico foram usados a fim de triar uma possível atividade antitumoral de TRY e DMT. Apesar de termos observado a expressão das enzimas DDC e INMT apenas na linhagem SK-Mel-147, ambas produziram triptaminas e metabolizaram TRY e DMT. Dependendo da linhagem houve a produção de ácido indolacético, DMT hidroxilado e produtos de abertura do anel indólico. Por fim, TRY e DMT diminuíram a migração e a proliferação das células tumorais. Há ainda muito a se estudar sobre a participação da TRY e DMT na biologia do tumor e as nossas descobertas ampliam o papel do metabolismo do triptofano no processo tumoral. / Tryptophan (TRP) metabolism occurs by three pathways: kynurenine, serotonergic and tryptamines paths. The first generates kynurenine and a range of secondary products and contributes to tolerance and tumor immune escape. Serotonergic pathway leads to the production of neuromediators and can generate melatonin. There are evidences that compounds of this pathway may control tumor growth. Tryptamines pathway originates tryptamine (TRY) and N, N-dimethyltryptamine (DMT) and represents the less-known route of TRP degradation. Thus, we investigated tryptamines pathway on human melanoma cell lines SK-Mel-19 and SK-Mel-147. Gene expression of the enzymes aromatic amino acid decarboxylase (DDC) and indoletilamina-N-methyltransferase (INMT), which convert TRP to TRY and DMT, respectively, was determined by real time PCR. The metabolites of this pathway were detected by LC/MS in cell culture supernatant. The scratch test and clonogenic assay were used to screen a potential antitumor activity for TRY and DMT. Although we have observed the expression of the enzymes DDC and INMT only on SK-MEL-147, both cells produced tryptamines and metabolized TRY and DMT. Depending on the cell line, products were indoleacetic acid (IAA), hydroxylated-DMT (OH-DMT) and indole opening ring products. Finally, TRY and DMT decreased tumor cells migration and proliferation. There is much to be studied about the participation of TRY and DMT in tumor biology, and our findings extend the role of tryptophan metabolism in tumoral process.

This thesis describes the development of a more economical catalytic system for the N-alkylation of amines by “borrowing hydrogen” and its application in the synthesis of a variety of amines including the dopamine agonist Piribedil and the antihistamine agents Antergan and Tripelennamine. <b>Chapter 2</b> describes the development of the ruthenium-catalysed N-alkylation of primary amines with primary alcohols by “borrowing hydrogen”. <b>Chapter 3</b> describes the application of the ruthenium-catalysed N-alkylation of secondary amines with primary alcohols by “borrowing hydrogen”. The ruthenium-catalysed synthesis of dimethylamines by “borrowing hydrogen” is also described and a mechanistic proposal for the N-alkylation of alcohols with amines has been proposed. <b>Chapter 4</b> describes the role of amines in pharmaceuticals and the ruthenium-catalysed synthesis of Piribedil, Antergan and Tripelennamine by “borrowing hydrogen”.

N-Nitrosodimethylamine (NDMA), which is a carcinogenic and toxic N-nitrosamine, can be found in water resources associated with a multitude of processes in various industrial facilities or merely as a by-product of water or wastewater treatment. Therefore, the removal of NDMA from drinking water represents an important human safety and public health concern. The present paper presents a density functional theory study of NDMA adsorption in all-silica MFI, Na-ZSM-5 and H-ZSM-5 zeolites. The stability of NDMA inside the zeolite pores was investigated by calculating the amount of energy released during adsorption. Various configurations of adsorbed NDMA to the zeolites were investigated, predominantly at the intersection of straight and sinusoidal channels. The strength of the adsorption energies followed the order H-ZSM5 > Na-ZSM-5 > all-silica MFI. NDMA has a dipole moment and the strongest binding of NDMA occurred through the interactions of the negatively charged O atom of the molecule to positive atoms of the zeolite. Similar calculations were performed for water adsorption in these three zeolites. The adsorption energy of water to these three structures followed the order Na-ZSM5 > H-ZSM-5 > all-silica MFI. We also incorporated van der Waals corrections in the simulations, which had the effect of stabilizing NDMA within the zeolite channels, but did not significantly change the relative stability of the different adsorption geometries. It was concluded that H-ZSM-5 is the best choice to remove NDMA because it is strong enough to adsorb NDMA and it is not too strong in adsorption of water molecules.

Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant genetic disorder that results from a mutation of one of two key signaling receptors for the transforming growth factor beta (TGFβ) superfamily: endoglin and activin receptor-like kinase 1 (ALK1). These mutations result in development of HHT Type 1 and HHT Type 2, respectively. Patients suffering from HHT experience spontaneous blood vessel growth that can lead to telangiectasia, arteriovenous malformation (AVM) development, and other related health problems. ALK1 is a serine/threonine kinase receptor found on the cell membrane of endothelial cells. ALK1 and its co-receptor endoglin, are activated by binding to the circulating BMP9 ligand. The ALK1-endoglin-BMP9 complex will then regulate endothelial proliferation by activating the SMAD pathway by phosphorylation. Mutations in the ACVRL1 gene can form a modified ALK1 protein that has a high potential to inhibit this function, causing the hyperproliferation of endothelial cells and the development of AVMs, and ultimately HHT Type 2. It is believed, however unproven, that ALK1 is heavily glycosylated in the extracellular domain. My thesis research was aimed at studying the glycosylation of ALK1 and at exploring the relevance of this glycosylation to the development of HHT. The glycosylation of ALK1 was investigated by using: (i) a computational prediction approach (NetNGlyc 1.0 bioinformatics server), (ii) a glycosylation inhibiting drug (tunicamycin), (iii) an in vitro enzymatic approach of glycosylation breakdown, and (iv) site-directed mutagenesis to identify the ASP residue glycosylated on ALK1. The bioinformatics software NetNGlyc predicted a N-linked glycosylation site on an asparagine (ASN) residue located at position 98 in the extracellular domain of ALK1. I further found that, based on western blot analysis, ALK1 proteins shifted to a lighter molecular weight (5-8 kDa) when treated with tunicamycin, as well as endo H and PNGase F enzymes, which represent two glycosidases able to remove N-linked oligosaccharides on proteins. Western blot analysis also revealed an identical shift in protein size (5-8 kDa) when comparing wild type ALK1 to an asparagine98-to-alanine (N98A) mutant ALK1 construct. The 5-8 kDa shift observed in the drug and enzymatic experiments indicate the removal of a bulky oligosaccharide from the wild type ALK1 protein. This 5-8 kDa shift observed in the mutagenesis experiment indicated that the same oligosaccharide addition could not occur on ALK1 when ASP98 was missing. Thus proving that the asparagine at the 98th position of ALK1 is involved in N-linked glycosylation. These important findings on ALK1 modification offer a greater understanding of the mechanisms behind ALK1 regulation and function, especially its role in controlling angiogenesis. Furthermore, this data provides grounds for further research into the importance of ALK1 glycosylation in the pathogenesis of HHT, as well as the investigation into new treatment regiments.