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.

Submitted by Angela Maria de Oliveira (amolivei@uepg.br) on 2018-04-20T12:04:40Z No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) Karla Miky.pdf: 833137 bytes, checksum: 4aac692850a86aaeabe93d6bbcf5af02 (MD5) / Made available in DSpace on 2018-04-20T12:04:40Z (GMT). No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) Karla Miky.pdf: 833137 bytes, checksum: 4aac692850a86aaeabe93d6bbcf5af02 (MD5) Previous issue date: 2018-03-09 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / O óleo de linhaça tem se destacado como alimento funcional para humanos, sendo a fonte mais rica de ácido graxo α-linolênico. Quatro dietas isentas de farinha de peixe foram formuladas para serem isoproteicas (321,2 g/kg de proteína brua), isocalóricas (17,1 Mcal/kg de energia bruta) e isolipídicas (73,1 g/kg de lipídios totais), contendo duas fontes de óleos vegetais (óleo de soja ou óleo de linhaça) suplementadas em dois níveis (15 ou 30 g / kg). Foram distribuídos ao acaso 144 peixes (1076,3 ± 37,2 g) em esquema fatorial 2x2, em 12 gaiolas flutuantes de 1000 L cada, alimentadas manualmente até saciedade aparente. Observou-se maior aumento de peso, consumo de ração e melhor conversão alimentar em peixes alimentados com 30 g/kg de óleo de linhaça em comparação com peixes alimentados com 15 e 30 g/kg de óleo de soja. O rendimento de filé foi maior em peixes alimentados com 30 g/kg de óleo de linhaça em relação aos peixes alimentados com 30 g/kg de óleo de soja. Não foram observadas diferenças no peso corporal inicial, índice hepatosomático e composição próxima dos filés. Peixes alimentados com 30 g/kg de óleo de linhaça apresentaram maior teor de 18: 3 n-3 e menor teor de 18:2n-6 nos filés em comparação com peixes alimentados com 15 e 30 g/kg de óleo de soja. As maiores somas de SFA, MUFA e AG n-3 foram observados em filés de peixes alimentados com 15 g/kg de óleo de soja. Peixes alimentados com 30 g/kg de óleo de linhaça apresentaram maiores somas de ácidos graxos PUFA e de ácidos graxos n-3 nos filés. Filés de peixes alimentados com óleo de linhaça apresentaram menor relação de ácidos graxos n-6/n-3 em comparação com peixes alimentados com óleo de soja. A cor, capacidade de retenção de água, pH e a dureza dos filés não foram afetados. A adesividade dos filés analisada um e sete dias pós mortem foi maior em peixes alimentados com óleo de linhaça, enquanto observou-se menor mastigabilidade em filés de peixes alimentados com 30 g/kg de óleo de soja e de linhaça em relação aos peixes alimentados com 15 g/kg de óleo de soja e linhaça. Em conclusão, o óleo de linhaça demonstrou ser um alimento funcional como fonte de AG α-linolênico e para aumentar a relação de ácidos graxos n-6/n-3 nos filés. Além disso, recomenda-se 30 g/kg de óleo de 8 linhaça em dietas de terminação para melhorar o desempenho produtivo de tilápias do Nilo em terminação. / Linseed oil has emerging as functional food for human being one richest source of α-linolenic fatty acid. Four fishmeal-free diets were formulated to be isonitrogenous (321.2 g/kg of crude protein), isocaloric (17.1 Mcal/kg of gross energy) and isolipidic (73.1 g/kg of total lipids), containing two sources of vegetable oils (soybean oil or linseed oil) supplemented at two levels (15 or 30 g/kg). A hundred and forty-four fish (1076.3 ± 37.2 g) were distributed in a completely randomized in a 2x2 factorial scheme, into twelve 1000 L each floating cage, hand fed until apparent satiety and reared at 18 to 24 oC, during 6 wk. Higher weight gain, feed intake and improved feed conversion ratio were observed in fish fed 30 g/kg of linseed oil compared to fish fed 15 and 30 g/kg of soybean oil. Fillet yield of fish fed 30 g/kg of linseed oil was higher compared to observed in fish fed 30 g/kg of soybean oil. No differences on initial body weight, hepatosomatic index and proximate composition of fillets were observed. Fish fed 30 g/kg of linseed oil showed higher 18:3 n-3 and lower 18:2 n-6 content in the fillets compared to fish fed 15 and 30 g/kg of soybean oil. Higher sum of SFA, MUFA and n-3 FA were observed in fillets of fish fed 15 g/kg of soybean oil. Fish fed 30 g/kg of linseed oil showed higher sum of PUFA and sum of n-3 fatty acids in the fillets. Fillet of fish fed linseed oil showed lower ratio of n-6/n-3 fatty acids compared to fish fed soybean oil. Color, water holding capacity, pH and hardness of fillets were not affected. The adhesiveness of fillets analyzed at one and seven days post-mortem was increased in fish fed linseed oil, while lower chewiness was observed in fillet of fish fed 30 g/kg of soybean or linseed oil compared to observed in fish fed 15 g/kg of soybean or linseel oil. In conclusion, linseed oil was demonstrated to be functional food as α-linolenic source to enhance n-6/n-3 ratio of the fillets. In addition, linseed oil at 30 g/kg is recommended in finishing diets

One of the primary focuses in the works presented and discussed herein is the juxtaposition of many disparate musical styles, recordings, and sound worlds within each individual piece. This juxtaposition extends to combining live improvisation meticulously created non-realtime elements, and elements of generative processes in the creation of individual works. A secondary theme is my attitude to accessibility and how this informs my work with audiovisual elements.

Made available in DSpace on 2014-06-12T17:40:02Z (GMT). No. of bitstreams: 2 arquivo7556_1.pdf: 1319814 bytes, checksum: 7a24f78f3fe9fcf10ae4520aa4b35406 (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) Previous issue date: 2006 / A indústria de Panificação é uma das mais antigas atividades desenvolvidas pelo Homem e nos primórdios das civilizações, todo o processo de fabricação era, naturalmente, artesanal e rudimentar. Com a evolução e o passar dos séculos, foi se aprimorando lentamente, até chegar aos dias de hoje em que a atividade de panificação dispõe de equipamentos e técnicas para seu fabrico, de uma vasta quantidade e crescente variedade de pães. Com o crescimento da população e o aumento na demanda por alimentos prontos para o consumo - incluindo-se nestes os pães - os governos foram forçados a editar leis a fim de adequar sua fabricação a normas regulamentares, visando assegurar a melhor qualidade do produto e forçar a observância de requisitos mínimos de higiene e sanitização. No Brasil, dentre essas normas, sobressai a Resolução n. 216 da Agência Nacional de Vigilância Sanitária, de setembro de 2004, com o objetivo de padronizar os trabalhos de limpeza e higiene de máquinas e equipamentos, higiene pessoal, limpeza de reservatórios e o controle de pragas urbanas. A este projeto foi dado o nome de Boas Práticas de Fabricação (BPF). Esta Resolução padroniza os trabalhos e exige dos estabelecimentos produtores a elaboração de manuais de produção e os procedimentos operacionais padronizados, concernentes aos itens acima referidos. A presente pesquisa tem por objetivo descrever os trabalhos de implantação das BPFs em 25 panificadoras da região metropolitana do Recife. No escopo desta dissertação relaciona-se uma vasta revisão bibliográfica sobre o assunto e a descrição, pari passu, dos trabalhos de campo realizados entre os meses de agosto de 2005 e agosto de 2006. De posse dos dados coletados no trabalho de campo, é possível demonstrar como a implantação das Boas Práticas de Fabricação e o treinamento dos manipuladores de alimentos podem auxiliar a obter melhores resultados para os próprios estabelecimentos e a benefício da população. Resultados estes que transcendem o objetivo da qualidade dos produtos e contribuem para o aumento da produtividade

Chapter one introduces N-heterocyclic carbenes (NHCs) and discusses their use as ligands for rare earth metal complexes, with particular emphasis upon compounds synthesised from 2009 until the present day. Chapter two details the synthesis and characterisation of the homoleptic scandium-NHC complex [Sc(L)3] (L = [OCMe2CH2(1-C{NCHCHNiPr})]). Reactions of [Sc(L)3] with boranes, CO2 and CS2 are described which exploit the relative lability of the Sc–Ccarbene bond and allow formation of [Sc(L)2(OCMe2CH2(1-B'C{NCHCHNiPr}))] (B' = 9-BBN, BPh3, B(C6F5)3, BH3), [Sc(OCMe2CH2(1-O2CC{NCHCHNiPr})3]n, [Sc(L)2(OCMe2CH2 (1-S2CC{NCHCHNiPr})] and [Sc(L)(OCMe2CH2(1-S2CC{NCHCHNiPr})2]2. The chapter also discusses the reactivity of [Sc(L)3] towards substrates containing acidic C–H and N–H bonds and substrates containing polar E–X bonds (where E = C, Si, B, P and X = Cl, I). Chapter three describes the synthesis and characterisation of the NHC substituted scandium benzyl complexes [Sc(Bn)2(L)]2 and [Sc(Bn)(L)2], and the attempted synthesis of NHC substituted scandium aminobenzyl complexes. The reactivity of [Sc(Bn)2(L)]2 with RX substrates (R = alkyl) is discussed in detail; depending on the nature of the alkyl group, these reactions can allow formation of R–Bn , the result of carbon-carbon coupling. The complex [Sc(Bn)(L)Cl]2 has been isolated from these reactions and is structurally characterised. The reactivity of [Sc(Bn)2(L)]2 towards C–H bonds is explored and attempts to prepare NHC substituted scandium hydrides are described. Comparisons of the relative stability and reactivity of [Sc(Bn)2(L)]2 and [Sc(Bn)3(thf)3] are drawn. Chapter four documents the synthesis and characterisation of [Sc(Odtbp)2(L)] (Odtbp = 2,6-di-tert-butylphenoxide), [Sc(Odtbp)(L)2], and the samarium analogue [Sm(Odtbp)(L)2]. The reactivity of these complexes towards various small molecules is described. The chapter also details attempts to prepare the cationic scandium complexes [Sc(L)2][Bort] (Bort = bis[3,3',5,5'-tetra-(tert-butyl)-2,2-diphenolato]borate) and [Sc(L)2][B(Ph)4]. Chapter five provides overall conclusions to the work presented in this thesis. Chapter six contains all experimental and characterising data for the complexes and reactions detailed in this work.

Considerando a necessidade de antipsicóticos mais seguros e eficazes, uma série de derivados N-fenilpiperazínicos funcionalizados e N-benziltiazolidínicos foi planejada e sintetizada pelo Laboratório de Avaliação e Síntese de Substâncias Bioativas (LASSBio-UFRJ) (LASSBio-1412, LASSBio-1413, LASSBio-1414, LASSBio-1415 e LASSBio-1422) e pelo Grupo de Pesquisa em Inovação Terapêutica (GPIT-UFPe) (FPY-1, FPY-2, FPY-3, FPY-5, FPY-6, FPT-1, FPT-2, FPT-4, FPW-1), respectivamente. Objetivos: selecionar os derivados com potencial atividade antipsicótica através do ensaio de climbing induzido por apomorfina, um modelo preditivo de sintomas positivos da esquizofrenia. Avaliar a ocorrência de efeitos motores e neurotoxicidade por catatonia e rota-rod. Avaliar possíveis efeitos adversos por locomoção e tempo de sono barbitúrico. Verificar o perfil de afinidade a receptores através de ensaios de binding. Métodos: para os ensaios de binding foram utilizados cérebros de ratos Wistar para os receptores D2-like, 5-HT1A e 5-HT2A e fígado de coelho e rato para os receptores α1A e α1B. Camundongos CF1 machos foram utilizados para os testes in vivo. As substâncias foram testadas no modelo de climbing induzido por apomorfina e apenas às substâncias capazes de inibir climbing foi dado continuidade ao estudo. Resultados: LASSBio-1412, LASSBio-1413, LASSBio-1422, FPT-2, FPT-4 e FPY-3 inibiram climbing, sem induzir sinais de catatonia, comprometimento motor, alteração do comportamento exploratório e efeito hipnótico-sedativo. Um estudo dose-resposta (0,5 - 30 mg/kg, v.o.) dessas substâncias indicou LASSBio-1412 como o composto mais potente in vivo. In vitro, observou-se que os derivados N-fenilpiperazínicos possuem uma moderada afinidade pelos receptores estudados, demonstrando um perfil de ligação multirreceptor; semelhante aos antipsicóticos atípicos. Por outro lado, os derivados N-benziltiazolidínicos possuem baixa afinidade por esses receptores, sugerindo um mecanismo de ação diferente. Conclusão: Essas moléculas podem representar protótipos promissores para o desenvolvimento de novos antipsicóticos. / Considering that more effective and safer drugs to treat schizophrenia are still needed a series of functionalized N-phenylpiperazines and N-benziltiazolidines derivatives were planned and synthesized by Avaliação e Síntese de Substâncias Bioativas Group (LASSBio/UFRJ): (LASSBio-1412, LASSBio-1413, LASSBio-1414, LASSBio-1415 and LASSBio-1422), and Núcleo de Pesquisa em Inovação Terapêutica Group/UFPE: (FPY-1, FPY-2, FPY-3, FPY-5, FPY-6, FPT-1, FPT-2, FPT-4, FPW-1), respectively. The aim of this study was to search the derivatives with potential antipsychotic activity through apomorphine-induced climbing test and binding receptor assaying as well as to evaluate their potential extrapyramidal sideeffects and neurotoxicity by catatonia and rota-rod tests. Adverse effects were also evaluated by open-field test and barbiturate sleeping time. Methods: Binding assays to D2-like, 5-HT1A, and 5-HT2A receptors were performed in brain rat regions and binding to α1A and α1B receptors were performed in rabbit and rat liver, respectively. All compounds were initially tested by mice apomorphine-induced climbing and only those able to inhibit climbing were selected to further studies. Results: LASSBio- 1412, LASSBio-1413, LASSBio-1422, FPT-2, FPT-4 and FPY-3 inhibited climbing without inducing catatonic behavior, general motor impairment, exploratory behavior alterations or hypnotic-sedative effect. A dose-responde study pointed LASSBio- 1412 as the most potent compound in vivo. In vitro, the N-fenilpiperazines derivatives demonstrated a moderate affinity to the studied receptors, demonstrating a multireceptor profile characteristic of atypical antipsychotics. In a different way, the Nbenziltizolidines derivatives have a low affinity to these receptors, suggesting that these compounds could be acting through a different action mechanism. Conclusion: These compounds are promising molecules to antipsychotics development.

A recent pattern has emerged amongst some of the top television production companies in the world – a global investment in a new style of television show format. Food television show formats such as Channel 4’s The Great British Bake Off in the UK and Fox’s Hell’s Kitchen in the US have consistently topped television ratings and attracted millions of viewers in every episode aired in their home counties and abroad. A range of publications argue that there has been a global demand for factual television formats, yet existing literature has focused primarily on dramas, talent shows and game show television format genres. From a production perspective, this thesis aims to respond to these industry changes and the gap in the literature by examining the media branding techniques employed by media managers that have contributed to the development of international food television show formats. It analyzes the distinct challenges and opportunities food television format producers of shows such as Endemol Shine Group’s MasterChef undergo when adapting food formats in international markets. Furthermore, it investigates production decisions around multi-platform strategies. This includes the adaptation of food television show formats onto multi-platform distribution channels such as catch up television like Netflix, Amazon Prime, format brand websites and social media channels like Facebook, Twitter, YouTube, and Instagram in order to acquire additional revenue streams. This thesis examines the managerial decisions that have helped aid the cooking show into becoming a successful, global television format. The research findings are based on a mixed-method qualitative approach featuring 15 qualitative interviews with industry experts from major production companies such as Endemol Shine Group and FremantleMedia and celebrity television chefs, such as BBC One’s MasterChef’s Gregg Wallace and former Food Network star, Paula Deen. The outcomes of this research provide an empirical analysis of the complex relationship between new media technologies, food television and the internationalization of global television formats. Furthermore, this thesis provides a snapshot of a specific and current media trend that exists within a wide scope of media industry practices and aims to provide valuable insights and build on existing media management, multi-platform, and media production theory.

The visual culture of Victorian Protestant missionaries is an under-researched area, despite the current interest in art and religion, and the implications of missionary imagery’s legacy in a post-colonial world. Looking specifically at British missionaries to southern Africa, this thesis proposes that visual culture, comprised of art, image, and their corollaries in personal and collective imagination, be recognised as an appropriate framework through which to re-examine a group predominantly associated with the Word. In particular, it argues that visual resources were not only communicated with originating missionary societies and home supporters, but were utilised as tools for evangelism and education, and the development of self-identity for men and women operating far from home. Beginning with a theoretical defence of visual culture as an appropriate and meaningful lens through which to investigate mission, the thesis goes on to consider the formative visual culture of prospective missionaries, identifying how and why evangelical Protestants accessed images. Key themes of landscape and portraiture are identified, and the varied media through which these were encountered investigated, including printed publications, gallery art, domestic ephemera, and ecclesial decorations. A detailed examination of the popular religious periodical The Sunday at Home brings together the exploration of these diverse themes. The second half of the thesis transitions from visual influences on prospective missionaries at home, to the visual culture of foreign missionary practitioners, pivoting on the activity of missionary training. An exploration of training reveals a disconnect between the importance of art and image in popular religious life, and a failure to address adequately their evangelistic applications. Moving into the final sections of the project, art and image re-emerge as significant, though the lack of guidance on their use is shown to have limited their co-ordination and effectiveness. Nevertheless, archive research in the UK, and field research in Malawi and South Africa, yielded sufficient material to demonstrate the particular importance of the landscape genre, and of the magic lantern as a crucial visual medium. Although visual materials were significant in the construction of missionary identity, and were heavily utilised in mission contexts, there was a widespread lack of engagement with, and distrust of, the visual, creating the complex and ambiguous interactions with which this thesis is ultimately concerned.