Dissertations / Theses on the topic 'Tpyp'

Thesis (M.S.)--University of Toledo, 2008.
Typescript. "Submitted as partial fulfillment of the requirements for the Master of Science Degree in Chemistry." "A thesis entitled"--at head of title. Bibliography: leaves 58-62.

In questa tesi si cercherà di analizzare se un’eventuale adesione al TPP sia negativa per l’agricoltura e la politica agricola giapponese. Il primo capitolo avrà lo scopo di riassumere brevemente le peculiarità della politica agricola giapponese. Si analizzerà l’organizzazione della Nokyo e come questa sia stata fondamentale per la mobilitazione elettorale, creando così un forte legame con il Jiminto e con il Ministro dell’agricoltura (MAFF). Verrà esaminato inoltre come la riforma elettorale del ‘94, quella amministrativa del ’99 e la liberalizzazione finanziaria, abbiano indebolito il potere della Nokyo e la sua influenza sui governi. Il secondo capitolo avrà l’obiettivo di descrivere sinteticamente i cambiamenti della politica agricola giapponese nel tempo. Cercando di capire se la decisione di aderire al TPP sia un fatto isolato oppure il risultato di un cambiamento già in atto della politica agricola giapponese. Il terzo capitolo intende fornire un’analisi del processo di liberalizzazione del mercato agricolo giapponese. Partirà dall’adesione al GATT, analizzandone i punti critici per l’agricoltura giapponese. Si soffermerà sul cambio di politica estera giapponese, basato dalla sottoscrizione di FTA, ed analizzerà come i prodotti agricoli vengono trattati in questi accordi e che impatto hanno avuto sull’agricoltura giapponese. Il quarto capitolo si concentrerà invece sul TPP. Fornirà una cronologia dell’evoluzione delle trattative per l’adesione al TPP dal governo Minshuto fino ad oggi col secondo governo Abe, si sottolineerà quali fattori hanno spinto il governo Abe ad iniziare le trattative. Si concentrerà in particolare sul TPP nell’ambito agricolo, analizzando in che modo potrebbe influenzare l’agricoltura giapponese e come i paesi già aderenti al TPP abbiano trattato i prodotti agricoli più sensibili. In seguito, esaminerà le posizioni dei principali partiti politici sul tema del TPP, approfondirà le ragioni dell’opposizione all’adesione, e la posizione della Nokyo. Infine si vedrà come si è evoluta l’idea del Jiminto passando da una posizione di opposizione al TPP ad una posizione favorevole, creando del dissenso all’interno del partito stesso. Nelle conclusioni cercherò di valutare se secondo quanto raccolto nei capitoli precedenti, un’adesione al TPP sia veramente negativa per l’agricoltura e la politica agricola giapponese.

L'exploration de la reaction d'hydroformylation du styrene en presence du complexe rhcl(co)(tpp) 2 (tpp = 1,2,5-triphenyl-1h-phosphole) a ete menee dans plusieurs directions : l'etude de la cinetique de reaction, l'identification des complexes impliques dans la reaction catalytique, la recherche des intermediaires reactionnels et la comparaison avec les systemes rh 4(co) 1 2/pph 3 et rh 4(co) 1 2/tpp. Le premier chapitre decrit l'appareillage utilise pour realiser l'etude cinetique (reacteur, capteurs, systemes de mesure et de regulation) et le logiciel d'acquisition des mesures. L'exploitation des resultats conduit a une equation de vitesse difficile a interpreter et a correler avec un mecanisme reactionnel. Dans le deuxieme chapitre, l'etude du melange reactionnel par les spectroscopie de rmn 1h, 3 1p et 1 3c, revele l'existence du complexe dinucleaire rh 2(-co) 2(co) 4(tpp) 2 et celle du complexe mononucleaire hrh(co) 2(tpp) 2, tous deux impliques dans de multiples reactions d'echanges intermoleculaires et conformationnels. Le chapitre 3 rassemble les analyses, par spectroscopie ir, des melanges reactionnels prepares sous differentes atmospheres gazeuses. Elles confirment l'existence des complexes reveles par l'etude rmn et permettent d'en preciser la geometrie. Le chapitre 4 resume la recherche des intermediaires reactionnels par les spectroscopies ir et de rmn. Les substitutions isotopiques ( 2h et 1 3c) revelent la reversibilite de la formation de complexes rhodium-alkyle, permettent la caracterisation de complexes rhodium-acyle et la mise en evidence de reactions parasites (effet inhibiteur sur la vitesse de reaction). Le chapitre 5 reprend l'analyse et le traitement des mesures cinetiques, a l'aide d'un logiciel de calcul adapte. Les resultats d'experiences complementaires, associes a ceux des chapitres precedents, permettent de proposer une equation generale de vitesse et un mecanisme reactionnel en bon accord.

Thesis: Ph. D. in Inorganic Chemistry, Massachusetts Institute of Technology, Department of Chemistry, 2015.
Vita. Cataloged from PDF version of thesis.
Includes bibliographical references.
Oxalic acid is a two-carbon diprotic acid that is toxic to humans. In large doses, it can cause death by poisoning, and in smaller doses over time it can lead to chronic renal disease, such as the formation of kidney stones, acute renal failure, as well as other complications such as crystalline arthritis. Current strategies to mitigate oxalate toxicity focus on diet management, though recent therapeutic studies have begun to focus on both probiotic as well as enzymatic treatments for the prevention of oxalate-related illnesses. The acetogenic bacterium Moorella thermoacetica has been known for some time to metabolize oxalate, though the unique enzyme responsible was only recently discovered. M thermoacetica employs an oxalate oxidoreductase (OOR) to oxidize oxalate to two molecules of C0 2, generating two low-potential electrons. OOR uses a thiamine pyrophosphate (TPP) cofactor to cleave the C-C bond, and three [4Fe-4S] clusters to capture and transfer the electrons produced. Both of these products from oxalate degradation, CO 2 and the low-potential electrons, allow M thermoacetica to grow via the Wood-Ljungdahl pathway for acetogenesis (also known as the reductive acetyl-CoA pathway). OOR is a member of the larger superfamily of 2-oxoacid:ferredoxin oxidoreductase (OFOR) enzymes. OFORs are found in microorganisms across all domains of life, and are responsible for performing a number of essential metabolic reactions, including the conversion of pyruvate to acetyl-CoA. Though, most OFORs require coenzyme A as a co-substrate, OOR is the exception to this rule, as it is capable of metabolizing oxalate without the aid of CoA. To aid in understanding this newly discovered enzyme, we have determined three crystal structures of OOR. These structures have allowed us to visualize the resting state as well as two reaction intermediates: an oxalate-TPP adduct and a C0 2-TPP adduct. Additionally, these structures have revealed dramatic protein conformational changes in the active site that are likely to facilitate catalysis. As OOR is only the second OFOR to be structurally characterized, these structures have provided a wealth of information about the larger OFOR superfamily as well as about this novel mechanism of oxalate metabolism.
by Marcus Ian Gibson.
Ph. D. in Inorganic Chemistry

Orientador: Regina Buffon
Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Química
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Resumo: Analisou-se a solução catalítica de um catalisador industrial de hidroformilação de olefinas através de espectroscopia RMN de P, eletroforese capilar, cromatografia em camada delgada, cromatografia gasosa acoplada à espectrometria de massas e espectrometria de massas de alta resolução, a fim de tentar determinar a natureza das espécies de ródio presentes na solução e entender o que estaria causando a desativação do catalisador. Contudo, as únicas afirmações que podem ser feitas é que a solução contém trifenilfosfina livre (TPP) e seu óxido. Análises da solução do catalisador reciclado antes e após lavagem com trietanolamina (TEA), por espectrometria de massas de alta resolução, mostraram a diminuição do pico em 515 m/z após a lavagem do catalisador reciclado (de 52 % no catalisador reciclado antes da lavagem para 9% após a lavagem com TEA), sugerindo que a espécie associada a esse pico seria a responsável pela desativação. Entretanto, sua análise por MSMS permitiu a identificação apenas da TPP livre, confirmando a grande complexidade do sistema. Como segunda etapa deste trabalho, foram avaliados diferentes tratamentos realizados na solução catalítica (que contém um catalisador industrial de hidroformilação de olefinas (Rh/TPP), também denominado de catalisador reciclado) capazes de reativá-la. Dentre os tratamentos empregados, destaca-se a solução de TEA ¿ 10% (1 parte catalisador: 1 parte solução TEA - 10% (massa) em água (v/v)). Testes catalíticos na hidroformilação do 1-hexeno mostraram que, sem tratamento, o catalisador reciclado permitiu alcançar um TON de 20.773 em 4 h e que, após tratamento com esta solução, o aumento do TON foi significativo (29.995), equiparando-se ao número de Turnover do catalisador Padrão, que está livre de desativadores (TON = 29.057). Esses resultados permitem concluir que a desativação ocorre principalmente devido à presença de cloretos ou ácidos carboxílicos e que o processo desenvolvido é eficiente para a reativação do catalisador
Abstract: A solution of an industrial catalyst for the hydroformylation of olefins was analyzed by 31P NMR spectroscopy, capillary electrophoresis, thin layer chromatography, gas chromatography/mass spectrometry and high resolution mass spectrometry in order to investigate the nature of the rhodium species and try to understand the causes of catalyst deactivation. However, only free triphenylphosphine (TPP) and its oxide could be precisely detected. Analyses of the recycled catalyst before and after washing with triethanolamine (TEA), by high resolution mass spectrometry, showed a decrease of the peak in 515 m/z after washing (52% of the recycled catalyst before washing to 9% after washing with TEA), suggesting that this peak could be associated to the species responsible for catalyst deactivation. However, MSMS analysis of this peak showed only free TPP, confirming the complexity of the system under study. In the second phase of this study, different treatments of the catalytic solution (containing the industrial catalyst for hydroformylation of olefins (Rh / TPP), also called recycled catalyst), susceptible to reactivate it, were evaluated. Among the tested treatments, a solution of TEA - 10% (1 part catalyst / 1 part solution TEA-10% (mass) in water (v / v)) showed good results. Without this treatment, the recycled catalyst presented a TON = 20.773, in 4 h, in the hydroformylation of 1-hexene. After treatment, the observed TON was 29.995, similar to that obtained with a standard catalyst, free of deactivators (TON = 29.057). Therefore, we can conclude that deactivation takes place mainlly due to the presence of chlorides or carboxylic acids, and the developed procedure is effective for the reactivation of the catalyst
Mestrado
Quimica Inorganica
Mestre em Química

The aim of this master thesis is to analyze the approaches of members of the North American Free Trade Agreement (NAFTA) to the Trans-Pacific Partnership (TPP). The work is divided into three chapters. The first chapter is devoted to the analysis of NAFTA, primarily to its creation and approaches of the individual members during negotiations, main provisions and objectives of this free trade area. The second chapter analyzes the main reasons that led the states to join NAFTA and their current positions within the zone. The last chapter is dedicated to TPP, its main provisions and position of NAFTA members in this agreement.

Šio darbo tikslas buvo ištirti antimikrobinių medžiagų ir daugiavaisčio atsparumo siurblių slopiklių poveikį bakterijų sąveikai su TPP+ jonais. Šiam tikslui pasiekti reikėjo ištirti antimikrobinių peptidų įtaką bakterinių apvalkalėlių laidumui, įvertinti M. smegmatis bakterijų apvalkalėlio sąveiką su TPP+ jonais ir jų pasiskirstymą veikiant šias polikatijoniniais junginiais bei ištirti daugiavaisčio atsparumo siurblių slopiklių įtaką TPP+ jonų pasiskirstymui abipus M. smegmatis bakterijų apvalkalėlio. Šio darbo metu buvo parodyta, kad peptidų pVEC ir cys-pVEC sąveika su gramneigiamųjų E. coli bakterijų apvalkalėliu beveik nesiskiria: peptidai mažai laidina E. coli bakterijų išorinę membraną, bet depoliarizuoja jų plazminę membraną. Peptidas pVEC depoliarizuoja ir gramteigiamųjų B. subtilis bei mikobakterijų M. smegmatis plazminę membraną. Be to, buvo parodyta, kad TPP+ jonų srautų tyrimai gali padėti įvertinti mikobakterijų energetinę būseną. Polimiksinas B – antibiotikas prieš gramneigiamąsias bakterijas – nelaidina mikobakterijų M. smegmatis apvalkalėlio TPP+ jonams, bet depoliarizuoja jų plazminę membraną. Daugiavaisčio atsparumo siurblių slopiklis chlorpromazinas veikia mikobakterijų M. smegmatis plazminę membraną depoliarizuojančiai ir sumažina ampicilino koncentracijas, reikalingas mikobakterijų augimo slopinimui. Nauji potencialūs DVA siurblių slopikliai neturi įtakos M. smegmatis ląstelių jautrumui ampicilinui, bet keletas junginių sąveikauja su TPP+ išmetančiais... [toliau žr. visą tekstą]
The aim of this work was to estimate the effect of membrane permeabilizing compounds and multidrug resistance pump inhibitors on interaction of bacterial envelope with TPP+ ions. To achieve the aim we worked on antimicrobial peptides and their interaction with bacterial envelopes, on estimation of interaction of M. smegmatis envelope with TPP+ ions and equilibration of these ions across mycobacterial envelope. We have found that antimicrobial peptides pVEC and cys-pVEC have very similar effect on the envelope of gram-negative E. coli cells. They have little permeabilizing effect on the outer membrane but effectively depolarize the plasma membrane of E. coli. The peptide pVEC has depolarizing effect on both B. subtilis and M. smegmatis plasma membrane. We described interaction of M. smegmatis envelope with TPP+ ions. Polymyxin B has no permeabilizing effect on the mycobacterial cell wall, but it depolarizes the plasma membrane of M. smegmatis. Multidrug resistance pump inhibitor chlorpromazine increases the efficacy of ampicillin against M. smegmatis and has a depolarizing effect on mycobacterial plasma membrane. New potential multidrug resistance pump inhibitors have no effect on M. smegmatis sensitivity to ampicillin, however some of the compounds interacted with TPP+ efflux pumps.

Thesis (Ph. D.)--Ohio State University, 2004.
Title from first page of PDF file. Document formatted into pages; contains xix, 193 p.; also includes graphics. Includes bibliographical references (p. 181-193).

[EN] In this Doctoral Thesis the reactivity of a group of emerging pollutants (EP) present in the output waters of urban treatment plants and the implementation of a photo-Fenton process in slightly acidic pH conditions using bio-organic solubles (SBO) as auxiliary chemicals have been studied. First, a mechanistic study was performed to investigate the role played by various reactive species in the oxidation of a mixture of emerging pollutants generated photochemically through advanced oxidation processes. These oxidizing species are the hydroxyl radical (OH), singlet oxygen (1O2) and the excited states of photocatalysts able to act through electron transfer processes. Results show that the EP degradation from the photo-Fenton process is too complex to be explained exclusively by the direct reaction of radical OH¿. More likely, OH radical reacts with further species present in the medium, so that long-lived radicals are generated and contribute to the degradation of EP or participate in chain processes. Rose bengal, known 1O2 generator, showed very low reactivity with EP under photochemical conditions. This fact together with the low values obtained for the rate constants in the reaction of 1O2 with EP, indicate that degradation of EP with singlet oxygen at these concentrations is very inefficient. Electron transfer processes studied using triphenylpyrylium (TPP+) and triphenylthiopyrylium (TPTP+) showed that degradation of EP were produced through the excited singlet and triplet states of the photocatalysts, slightly higher results were obtained by using the TPTP+. SBO, isolated from the wet fraction of municipal waste, are formed by a mixture of macromolecules with a wide range of sizes that goes from 67 to 463 kgmol-1. Furthermore, chemical composition of SBO resembles that of natural organic matter that has been employed in solar photochemical processes for wastewater treatment. Characterization of SBO has shown that these substances are biocompatible, stable after 24 hours of irradiation and able to improve the efficiency of photo-Fenton under slightly acidic pH. The results obtained in the optimization of the operational variables of the photo-Fenton process in the presence of SBO suggest that the mechanism of this process has changed, so that the optimum pH value of 2,8 has shifted to values close to 4. Therefore, the hydroxyl radical is not the main specie but others species could play a role; however they have not been unequivocally identified due to the complexity process. Moreover, SBO are able to generate reactive species; however their efficiency depends on the balance between the generation of reactive species and the inner filter effect produced by the deep color of SBO and also by the competition for the generated reactive species between SBO and the pollutants
[ES] En la presente Tesis Doctoral se estudió la reactividad de un conjunto de contaminantes emergentes (CE) presentes en aguas naturales de salida de depuradoras urbanas y la posibilidad de implementar un proceso foto-Fenton en condiciones de pH ligeramente ácidas empleando sustancias solubles bio-orgánicas (SBO) como auxiliares químicos. En primer lugar se realizó un estudio mecanístico para indagar sobre el papel desarrollado por diversas especies reactivas, generadas fotoquímicamente mediante procesos de oxidación avanzada, en la oxidación de una mezcla de contaminantes emergentes. Entre estas especies oxidantes se encuentra el radical hidroxilo (OH.), el oxígeno singlete (1O2), y los estados excitados de los fotocatalizadores capaces de actuar en procesos de transferencia electrónica. Los resultados obtenidos muestran que el proceso de degradación de los CE mediante foto-Fenton es demasiado complejo para poder ser explicado únicamente mediante la reacción directa del radical OH. Posiblemente, tras ser generado, el radical OH reacciona con las especies presentes en el medio de forma que se generan radicales de vida larga que contribuyen a la degradación de los CE o bien inicia procesos en cadena. El rosa de bengala, conocido generador de 1O2, mostró muy baja reactividad con los CE en condiciones fotoquímicas. Este hecho unido a los bajos valores obtenidos para las constantes de reacción del 1O2 con los CE, nos indica que la degradación mediante reacción con oxígeno singlete a estas concentraciones es muy ineficiente. Los estudios de los procesos de transferencia electrónica empleando trifenilpirilio (TPP+) y trifeniltiopirilio (TPTP+) muestran que la degradación de los CE se produce desde los estados excitados singlete y triplete de los fotocatalizadores, obteniéndose unos resultados ligeramente superiores mediante el empleo del TPTP+. Los SBO son materiales extraídos de la fracción húmeda de los residuos urbanos. Estas sustancias están constituidas por una mezcla de macromoléculas con un amplio rango de tamaños que oscila de 67 a 463 kgmol-1. Además su composición química presenta similitudes estructurales con algunas sustancias que se encuentran en la materia orgánica natural y que han sido empleadas en procesos fotoquímicos solares para el tratamiento de aguas residuales. La caracterización de los SBO ha demostrado que estas sustancias son biocompatibles, estables tras 24 horas de irradiación y capaces de mejorar la eficiencia del foto-Fenton en condiciones de pH ligeramente ácidas. Los resultados obtenidos en la optimización de las variables operacionales en el proceso foto-Fenton en presencia de SBO sugieren que se ha producido una modificación en el mecanismo del proceso foto-Fenton de forma que se ha desplazado el valor óptimo de pH desde 2,8 a valores cercanos a 4. Por tanto el radical hidroxilo puede no ser la especie principal y entrar en juego otras especies que no han podido ser identificadas con certeza debido a la complejidad del proceso. Los SBO son capaces de generar especies reactivas, sin embargo se ha de llegar a un equilibrio entre la generación de especies reactivas y el efecto filtro producido por su acusada coloración, así como por la competencia de los propios SBO por las especies reactivas generadas.
[CAT] En la present Tesi Doctoral es va estudiar la reactivitat d'un conjunt de contaminants emergents (CE) presents en aigües d'eixida de depuradores urbanes i la possibilitat d'implementar un procés foto-Fenton en condicions de pH lleugerament àcides emprant substàncies solubles bio-orgàniques (SBO) com auxiliars químics. En primer lloc es va realitzar un estudi mecanístic per indagar sobre el paper desenvolupat per diverses espècies reactives, generades fotoquímicament mitjançant processos d'oxidació avançada, en l'oxidació d'una mescla de contaminants emergents. Entre aquestes espècies oxidants es troba el radical hidroxil (OH), l'oxigen singlet (1O2), i els estats excitats dels fotocatalitzadors capaços de actuar per processos de transferència electrònica. Els resultats obtinguts mostren que el procés de degradació dels CE mitjançant foto-Fenton és massa complex per poder ser explicat únicament per la reacció directa del radical OH. Possiblement després de ser generat, el radical OH reacciona amb les espècies presents en el medi de manera que es generen radicals de vida llarga que contribueixen a la degradació dels CE o bé inicia processos en cadena. El rosa de bengala, conegut generador de 1O2, va mostrar molt baixa reactivitat amb els CE en condicions fotoquímiques. Aquest fet unit als baixos valors obtinguts per a les constants de reacció del 1O2 amb els CE, ens indica que la degradació mitjançant reacció amb oxigen singlet a aquestes concentracions és molt ineficient. Els estudis dels processos de transferència electrònica utilitzant trifenilpirili (TPP+) i trifeniltiopirili (TPTP+) mostren que la degradació dels CE es produeix per mitjà dels estats excitats singlet i triplet dels fotocatalitzadors, obtenint uns resultats lleugerament superiors mitjançant l'ús del TPTP+. Els SBO són materials obtinguts de la fracció humida dels residus urbans. Aquestes substàncies estan constituïdes per una barreja de macromolècules amb un ampli rang de pesos moleculars que van de 67 a 463 kgmol-1. A més la seva composició química presenta similituds estructurals amb algunes substàncies que es troben en la matèria orgànica natural i que han sigut utilitzades en processos fotoquímics solars per al tractament d'aigües residuals. La caracterització dels SBO ha demostrat que aquestes substàncies són biocompatibles, estables després de 24 hores d'irradiació i son capaços de millorar l'eficiència del foto-Fenton en condicions lleugerament àcides. Els resultats obtinguts en l'optimització de les variables operacionals en el procés foto-Fenton en presència de SBO semblen suggerir que s'ha produït una modificació en el mecanisme de manera que s'ha desplaçat el valor òptim de pH des 2,8 a valors propers a 4. Pertant el radical hidroxil deixa de ser l'espècie principal i entren en joc altres espècies que no han pogut ser identificades amb certesa a causa de la complexitat del procés. Els SBO són capaços de generar espècies reactives, però s'ha d'arribar a un equilibri entre la generació d'espècies reactives i l'efecte filtre produït per la seua acusada coloració, així com per la competència dels propis SBO per les espècies reactives generades.
Gomis Vicens, J. (2015). Efecto de distintas especies reactivas generadas fotoquímicamente sobre la eliminación de contaminantes presentes en aguas naturales [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/51667
TESIS

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O desenvolvimento de sistemas de administração de fármacos utilizando biopolímeros, como a goma de cajueiro e quitosana tem-se destacado pela formação de nanoestruturas por complexação polieletrolítica, realizada pela interação das diferentes cargas dos materiais e devido as suas promissoras propriedades, dentre elas: excelente biodegradabilidade, elevada biocompatibilidade, baixa toxicidade. Usados no desenvolvimento nanotecnológico de formulações para proteção de fármacos peptídicos, como a insulina, para sua administração por via oral, no qual faz-se necessário pela sua instabilidade em variações de pH. Este trabalho teve como objetivo a síntese de nanopartículas a partir de biopolímeros por complexação polieletrolítica para administração oral de insulina e avaliação analítica do fármaco e seu principal produto de degradação o A-21 em meio ácido. Nanopartículas de goma de cajueiro e quitosana foram sintetizadas por complexação polieletrolítica com e sem adição do tripolifosfato de sódio, como agente de reticulação. Foram caracterizadas quanto ao seu tamanho, carga superficial, índice de polidispersão e adicionalmente a Espectroscopia da Região do Infravermelho (FTIR), Microscopia Eletrônica de Varredura (MEV), Análise Termogravimétrica (TG). Para a determinação analítica da insulina e seu principal produto de degradação o A-21 foi realizado um planejamento experimental fatorial, a fim de analisar quais variantes iriam influenciar para obtenção de um menor tempo de análise das moléculas por HPLC. Vinte e sete experimentos foram realizados e destacou-se dentre os valores observados nos tempos de retenção de 5,18 min para insulina e 9,10 min para o A-21, na condição onde a temperatura da coluna foi de 35°C, fluxo do eluente de 1,0 mL/min-1 e na proporção da fase móvel de 52% KH2PO4, 31% acetonitrila e 17% metanol, uma análise final com cerca de 11 minutos. Em média os fatores que mais influenciaram no sistema foram o fluxo do eluente e a proporção da fase móvel, demonstrados através da estimativa dos efeito, análise da variância e teste F. O modelo linear obtido demonstrou ter uma boa predição para o método, com pontos reais de distribuição aleatórios condizentes aos resultados obtidos experimentalmente, a variância total explicada de 91,14% e o modelo deixa de explicar 8,86% dos resíduos. A adequabilidade cromatográfica da combinação das variáveis independentes resultaram em valores próximos ou dentro dos limites estabelecidos. Os resultados das avaliações de concentração dos biopolímeros, proporção dos agentes de reticulação, ordens de adição, pH das soluções mostraram-se bastante significativos na influência dos tamanhos das partículas, potencial zeta e índice de polidispersão. Houve uma grande distinção das preparações com e sem TPP, pois foi evidenciada uma eficaz ação reticulante entre os polieletrólitos, as ligações cruzadas realizadas foram importantes para aperfeiçoamento dos parâmetros, demonstrado a redução dos tamanhos das nanopartículas, de modo homogêneo e com baixos índices de polidispersão, potenciais zeta na faixa neutra diferindo nos valores de acordo com a concentração adicionado. Através das caracterizações realizadas por FTIR, MEV e TG houve a demonstração da interação entre os materiais estudados. As características e propriedades apresentadas pelas nanoesferas formadas pela interação GC/TPP/QT indicam um promissor sistema de liberação de fármacos e proteção para moléculas instáveis ao ambiente gastrointestinal.
The development of drug delivery systems using biopolymers such as cashew gum and chitosan it has been highlighted by the formation of nanostructures by complexation polyelectrolytic held by the interaction of the different loads of materials and due to their promising properties, among them: excellent biodegradability , high biocompatibility, low toxicity. Used in nanotechnological development of formulations for protection peptide drugs such as insulin, for administration orally, in which it is necessary for its instability at pH variations. This study aimed to the synthesis of nanoparticles from biopolymers by complexation polyelectrolytic for oral administration of insulin and analytical evaluation of the drug and its main degradation product A-21 in acid. cashew gum and chitosan nanoparticles were synthesized by complexation polyelectrolytic with and without addition of sodium tripolyphosphate as crosslinking agent. They were characterized as to their size, surface charge, polydispersity and additionally Spectroscopy Infrared Region index (FTIR), Scanning Electron Microscopy (SEM), Thermogravimetric Analysis (TG). For the analytical determination of insulin and its main degradation product A-21 factorial experimental design was conducted to analyze variants which would influence to obtain a shorter analysis of molecules by HPLC. Twenty-seven experiments were conducted and it was highlighted among the values observed at 5.18 min retention time of 9.10 min for insulin and A-21 in the condition where the column temperature was 35 ° C, flow of the eluent of 1.0 ml / min-1 and the rate of mobile phase of 52% KH2PO4, 31% acetonitrile and 17% methanol, with a final analysis about 11 minutes. On average the factors that most influence the system were the eluent flow and the proportion of the mobile phase, demonstrated by estimating the effect of variance analysis and test F. The resulting linear model was shown to have a good prediction for the method, with points real random distribution consistent with the results obtained experimentally, the total explained variance of 91.14% and the model fails to explain 8.86% of the waste. Chromatographic suitability of the combination of the independent variables resulted in close to or within the established limits. The results of evaluations concentration of biopolymers, the proportion of cross-linking agents, addition orders, the solutions pH were quite significant in the influence of particle size, zeta potential and molecular weight distribution index. There was distinction of preparations with and without TPP, as was evidenced effective action crosslinking of polyelectrolytes, cross-connections made were important for improvement of the parameters shown to reduce the size of the nanoparticles, homogeneous way and with low levels of polydispersity, zeta potential in the neutral range in differing values according to the concentration added. Through the characterizations made by FTIR, SEM and TG was the demonstration of the interaction between the studied materials. The characteristics and properties presented by the nanospheres formed by the interaction GC / TPP / QT indicate a promising system of drug delivery and protection for unstable molecules to the gastrointestinal environment.

México ante el Acuerdo Transpacífico (TPP); riesgos y oportunidades para la industria Textil del Estado de Puebla
El Acuerdo Transpacífico de Cooperación Económica, (TPP, por sus siglas en inglés) se puede considerar como un acuerdo comercial de vanguardia con conceptos relevantes dentro del siglo XXI. Es necesario tomar en cuenta que dicho acuerdo no entrará en vigor de inmediato, lo que implica un tiempo a transcurrir antes de su implementación. Dejando ver así, que, durante este periodo de aprobación, deben analizarse tanto los riesgos como las oportunidades para los sectores productivos que se encuentran siendo negociados en el mismo. La información obtenida mediante esta investigación puede servir como una visión más amplia sobre los riesgos y oportunidades que la industria textil poblana mantendría dentro de dicha negociación. No obstante, cada uno de los datos tomados, así como las comparaciones estadísticas se mantienen como una función prioritaria para la investigación. En el presente ensayo se ha realizado una investigación en el estado de Puebla a través de la Cámara Industria Textil de Puebla y Tlaxcala, (CITEX) mediante un pequeño cuestionario y revisión de archivos históricos, con el fin de saber el desarrollo que el sector textil y del vestido mantiene, así como también los riesgos y oportunidades que pudiera tener el sector en caso de una futura negociación. Algunos de los resultados nos dejan ver una visión más amplia hacia la forma en la que se ha desarrollado la industria desde sus inicios hasta nuestros días actuales, al mismo tiempo que nos mantiene actualizados y atentos en los riesgos que se pudieran tener. Al igual, se han obtenido resultados y estrategias a proponer para mejorar el desarrollo y combate ante las amenazas encontradas. Toda esta investigación ha sido posible gracias a las diferentes comparaciones históricas y estadísticas, proporcionadas por los directivos del (CITEX) así como la información obtenida dentro de la plataforma del Instituto Nacional de Estadística y Geografía, al igual que la revisión de los archivos históricos que se utilizaron para la consulta del presente.

Mitochondria are organelles present in eukaryotic cells that play a key role in regulating cells’ metabolic processes as well as cell death. The main function of mitochondria is to produce ATP, by oxidizing nutrients in a process called oxidative phosphorylation (OXPHOS). Besides this, mitochondria also play a critical role in calcium homeostasis, cell signaling, and apoptosis. Mitochondrial dysfunction is implicated in a plethora of diseases including neurodegenerative diseases, metabolic disorders as well as ageing and cancer. The triphenylphosphonium (TPP+) moiety has been used as a carrier to direct a wide variety of therapeutic and diagnostic cargo to mitochondria, in an effort to study and treat mitochondrial dysfunction. Studies in recent years show that TPP+ is not an inert carrier as previously thought. Many TPP+ conjugates have been shown to exert a negative effect on mitochondrial and cellular bioenergetics by decreasing the efficiency of OXPHOS. This phenomenon is called ‘mitochondrial uncoupling’. While mitochondrial uncoupling is undesirable for the TPP+ moiety to function as a carrier of cargo to mitochondria, controlled uncoupling has therapeutic applications in treatment of obesity and cancer. The extent of mitochondrial accumulation as well as potency of mitochondrial uncoupling caused by the TPP+ moiety increases with increasing length of the linker functionality in TPP+ conjugates. Most of the studies to date have focused on altering the linker length of the TPP+-linker-cargo conjugate to optimize the balance between safety and efficacy. However, very little is known about how structural modification of the TPP+ moiety itself affects mitochondrial uncoupling potency. Therefore, there is a need to understand the structure activity relationship (SAR) between modification of TPP+ structure and the effect of these structural changes on mitochondrial uncoupling and uptake. Towards this end, the first goal of this study was to understand the effect of modulating electron density on the phosphorus atom of TPP+ on the potency of uncoupling OXPHOS. Modifications to the TPP+ moiety included substitution of electron withdrawing and donating groups on the phenyl rings of TPP+, and replacing phenyl rings with bulkier napthyl rings. Modified TPP+ moieties were conjugated to five different linkers, which varied in length and lipophilicity, and the effect of these conjugates on mitochondrial bioenergetics was studied. The second goal of the study was to evaluate if the propensity of TPP+ to uncouple mitochondrial respiration can be modulated, independently of mitochondrial uptake. For this purpose, the uptake of modified TPP+-linker conjugates into isolated mitochondria and the uptake of fluorescently labeled modified TPP+-linker conjugates into mitochondria within whole cells was investigated. The ability of modified TPP+ to protect cells from oxidative stress by successfully delivering an anti-oxidant cargo to mitochondria within cells was also assessed. The results of these studies establish the first SAR for modulating TPP+ structure to either eliminate, optimize, or maximize uncoupling of mitochondrial OXPHOS, and led to identification of lead molecules for potential applications in the fields of mitochondrial delivery, anti-obesity therapy and anti-cancer therapy.

Preliminary NMR data indicate that a new platinum compound, assigned (TpyO)PtMe (TpyO = 2,6-bis-(2’pyridyl)-4-pyridonate), can be synthesized by the addition of impure trans-(DMSO)2PtMeCl to impure 2,6-bis(2’-pyridyl)-4-hydroxypyridine (TpyOH) in the presence of NEt3 in about 10% yield. It is likely that the yield could be increased by using purified TpyOH and (DMSO)2PtMeCl. The metalation step of the synthesis was also attempted using (COD)PtMeCl but was unsuccessful with either Na2CO3 or NEt3 as bases, most likely due to the chelate effect of the bidentate COD. Future work with (TpyO)PtMe will include the addition of H+/D+ to generate the platinum (IV) complex, [(TpyO)Pt(Me)(H)]+, and/or the σ-complex [(TpyO)Pt(Me-H)]+ in order to examine the kinetic, isotope, and thermodynamic effects of the resulting reductive elimination reaction.

This research studies the relationship between car manufacturers (CM) and third party logistics providers (TPLP), also known as the logistics partnership, in the outbound delivery channel in the Malaysian automotive industry. It focuses specifically on the dyad perspective, and demonstrates that several critical success factors are required for a successful relationship between these two parties. Five such factors emanate from the operational dimension and eight from the relational dimension. The five operational factors are: logistics service performance, investment, information sharing, information technology and communication, and price of the logistics service; and the eight relational factors are: trust, commitment, power, conflict, dependency, co-operation, informal activity, and understanding. The study also reveals that five outcomes are identified that benefit both the CM and the TPLP as a result of the win-win situation accruing to both parties. These are: renewal of the contract, company profitability, improved logistics service performance, knowledge transfer, and company branding. Such benefits enhance the supply chain relationship, and knowledge of these advantages improves current TPLP theory by deepening the understanding of how logistics partnership can succeed. In order to obtain rich data concerning the CM-TPLP relationship, the researcher adopted a different methodology from that used by previous scholars, who have concentrated on quantitative techniques. In this study, multiple case studies (seven in total) in one industry, the automotive industry, in the non-western context of Malaysia, were conducted. Three main steps in the case study protocol were followed. The first involved a review of the literature pertaining to the themes that required further exploration, together with the development of the interview questions. In the second step, data were collected using semi-structured interviews, observations, document reviews, photographs and also archival records. Qualitative content analysis was used to analyse the qualitative data. The third stage involved exploring the data until it was found that nothing new was emerging from the interviews, and hence theoretical saturation had occurred. At this point the factors in question were confirmed, and the initial model revised. Additionally, confidentiality was maintained in all respects to protect the participating organisations and individuals. The findings contribute to the understanding of the CM-TPLP relationship which enhance supply chain relationship and TPLP theory, since they shed light on the operational and relational factors in one specific industry, from a dyadic perspective, and in a non-Western context, thereby adding new dimensions to the existing body of knowledge in this field. The findings benefit practitioners via the novel LPS (logistics partnership success) model generated by the researcher. This indicates the key contributory factors to the CM-TPLP relationship success. Moreover, the study may have the capacity to generalise to other culturally-similar environments.

No presente trabalho foram realizados estudos para verificar a estabilização de derivados porfirínicos, através de sua incorporação em lipossomos fosfolipídicos ou sintéticos, para possível aplicação em terapia fotodinâmica. A terapia fotodinâmica ocorre através da interação de luz de comprimento de onda adequado com um fotosensitizador (porfirina) e oxigênio, o que pode gerar espécies reativas capazes de induzir a inviabilização de células. Foi avaliada a incorporação da benzoporfirina (BPD) e da meso-tetrafenilporfirina (TPP), em lipossomos aniônicos de asolecitina (ASO) e em vesículas catiônicas sintéticas de brometo de dioctadecildimetilamônio (DODAB). Os efeitos de concentração da droga e dos lipídios, na estabilização das porfirinas também foram observados. A solubilização e a estabilidade da BPD e da TPP nas bicamadas lipossomais foram comparadas com sua solubilização e estabilidade nos seus respectivos solventes, o dimetilsulfóxido (DMSO) e a dimetilformamida. (DMF), respectivamente. Os estudos demonstraram uma boa solubilização da BPD, e ótima solubilização da TPP, incorporadas em soluções aquosas de vesículas catiônicas sintéticas de DODAB e nos lipossomos aniônicos de ASO, em toda a faixa de concentrações estudadas. Foram ainda verificados possíveis danos aos próprios lipossomos de ASO, através da formação de derivados carbonílicos (método TBARS e método da formação de hidrazonas), em vários tempos de irradiação. Resultados após tratamento fotoquímico foram comparados a resultados análogos, após tratamento térmico. Também foi verificado se os compostos estudados são capazes de gerar oxigênio singleto, que podem danificar membranas, visando possível aplicação oftalmológica dessas porfirinas. Os resultados obtidos mostraram que predominantemente a ação da TPP e da BPD deve ocorrer pelo mecanismo de formação de oxigênio singleto (mecanismo II). O mecanismo tipo I parece não ser ativo, já que os danos oxidativos observados através de radicais livres foram muito semelhantes tanto com tratamento fotoquímico, como térmico.
In this work, it was carried out studies in order to evaluate the estabilization of porphyrinics species by encapsulating them in liposomes or synthetics for application in photodynamic therapy (PDT). In PDT a monochromatic light at a suitable wavelenght interacts with photosensitizer (porphyrin) and oxygen yelding reactives species which induce cells killing. It was evaluated benzoporphyrin (BPD) and tetraphenilporphyrin (TPP) incorporation in the liposomes anionics of asolecithin (ASO) and vesicles cationics synthetics of dioctadecyldimethylammonium (DODAB). It was also noticed the drug and lipids concentration effects in the porphyrins estabilization. BPD and TPP their solubilization and estabilization in the in the liposomal bilayers were compared with the results obtained in their best solvents dimethylsulfoxide (DMSO) and dimethylformamide (DMF). TPP was better soluble than BPD when they were encapsulated in DODAB and ASO in all concentration range that was studied. It was characterized possible damages in the ASO by formation carbonyl groups (method TBARS and method to form hydrazones), when the samples irradiated in differents timeintervals. The results reached after photochemical treatment were compared to similar results found after thermal treatment. It was also evaluated if the studied compounds are able to generate singlet oxygen that can cause damages to the menbranes pursueing the possible application in ophthalmology. The results suggest that the TPP and BPD act mainly by singlet oxygen producting (mechanism type II). The type I mechanism seems not to be active, because the oxidative damages caused for free radicals were very similar by photochemical treatment or thermical treatment.

Lo studio, facendo uso delle coalizioni discorsive come teorizzate da Maarten Hajer, analizza il discorso pubblico rispetto all’autosufficienza e alla sicurezza alimentare nel contesto della discussione riguardo il TPP avvenuta in Giappone. Vengono individuate due coalizioni con una narrativa distinta. Da una parte il triangolo di ferro del settore agricolo e gruppi di cittadini che dipingono il trattato come rischioso per il Giappone in quanto porterebbe al collasso del mercato agricolo. Dall'altra, il governo centrale, individuato nella figura degli uffici dell’allora Primo Ministro Abe, affiancato dal Ministero degli Affari Esteri e dal Ministero del Commercio che sottolineano come una maggiore liberalizzazione porterebbe dei benefici al settore agricolo. Lo studio introduce il contesto che ha portato alla creazione di un ambiente adeguato alla nascita di una nuova narrazione. Vengono poi presentati gli strumenti che sostenevano l’egemonia della narrazione dominante e quelli che hanno permesso di dare vita ad un nuovo discorso. Le narrazioni delle due coalizioni saranno poi esposte. Lo scopo ultimo della tesi è verificare il cambiamento del discorso dominante nel post-TPP analizzando le politiche estere e le riforme agricole compiute del governo Abe.

La régulation de l’expression génétique est essentielle afin qu’un organisme puisse s’adapter aux changements environnementaux. Chez les bactéries, la régulation peut s’effectuer à plusieurs étapes de l’expression des gènes (transcription, stabilité de l’ARN, traduction, maturation et dégradation des protéines) et par des mécanismes impliquant différents types de molécules (ADN, ARN, protéines, métabolites ou ions inorganiques). Traditionnellement, les protéines se situaient au centre de ces mécanismes de régulation. On sait maintenant que certains ARN, dont les riborégulateurs, ont également un grand rôle à jouer dans ce processus. Un riborégulateur est un élément génétique retrouvé dans une région non-codante de certains ARN messagers (ARNm), qui peut lier directement un ligand spécifique afin de réguler l’expression de son transcrit. Chez Escherichia coli (E. coli), trois riborégulateurs lient la thiamine pyrophosphate (TPP). Un d’entre eux, le riborégulateur thiB, n’a toujours pas été étudié. On croit qu’il contrôlerait, au niveau de l’initiation de la traduction, l’expression de l’opéron thiBPQ encodant un transporteur ABC de la thiamine. De plus, un petit ARN nommé SroA a précédemment été identifié grâce à des techniques de séquençage d’ARN. SroA correspond à l’aptamère du riborégulateur thiB, mais aucun rôle ne lui a été attribué à ce jour. Le présent mémoire porte sur la caractérisation du riborégulateur thiB d’E. coli. Dans un premier temps, nous avons démontré que le riborégulateur est fonctionnel. Le mécanisme permettant la régulation génétique en cis est cependant plus complexe que seulement la régulation prédite au niveau traductionnel. Dans un second temps, nous avons utilisé deux approches différentes à l’échelle transcriptomique afin de vérifier si SroA régule l’expression de certains ARNm en trans. Plusieurs cibles potentielles découlent de cette étude. Une caractérisation préliminaire de certaines d’entre elles est présentée ici et devra être poursuivie par des travaux subséquents. Les résultats présentés ici suggèrent que le riborégulateur thiB régulerait l’expression de l’opéron thiBPQ (en cis) et d’autres gènes en trans.

Over 400 million people are currently affected by parasitic worm infections. While seldom fatal, the long-term consequences of helminthiases are significant and global burden is estimated at 22 million disability adjusted life years per annum. Amid growing concerns of zoonosis, treatment resistance and geographical expansion, there has been a call for the development of novel anti-parasitic strategies. To minimise potential treatment side effects, common approaches target proteins that are essential for parasite survival but absent from the host genome. One such target is the essential enzyme trehalose-6-phosphate phosphatase (TPP), the final enzyme in the trehalose biosynthesis pathway. TPP is essential for roundworm survival, a validated target for the treatment of tuberculosis and also shows promise as a vaccine against the nematode Brugia malayi, the causative agent of lymphatic filariasis. This work focuses on the TPP enzymes of the parasitic nematodes Toxocara canis and Ancylostoma ceylanicum as the centre of a target-based approach to identify novel TPP inhibitors with potential as early drug discovery leads. Structure-based sequence analysis of the TPP enzymes of a range of pathogens supported the proposal of three topological groups with structural differences and revealed species-specific variation in what is otherwise considered a highly conserved enzyme family. To account for interspecies variation during downstream drug discovery work, the TPPs of Mycobacterium tuberculosis, Stenotrophomonas maltophilia and Pseudomonas aeruginosa were added to the study, forming a panel of nematode and bacterial TPPs. Enzymatic characterisation of these enzymes revealed that they are kinetically suited to their physiological function and largely employ superstoichiometric burst kinetics, which suggests a role for conformational change during catalysis. To identify novel scaffolds for TPP inhibition, 5,452 compounds were screened as potential TPP ligands. Of these, 222 compounds (4% selection rate) were selected and tested for TPP inhibition in vitro. This work culminated in the identification of a series of novel TPP inhibitors based on three chemical scaffolds, with low-micromolar inhibition constants and structures amenable to further development. The specificity of these compounds suggests that some may provide avenues for cross-species control of a range of parasitic diseases, while others may be leveraged to target only the nematode enzymes. One compound was found to be a species-specific suicide inhibitor of the nematode TPPs and has potential applications as a control or probe molecule in future TPP assay development. Two additional compounds were found to inhibit TPP via a mixed-type ‘competitive noncompetitive’ mechanism, which suggests the presence of an additional binding site distal to the active site. Based on structure-activity analysis, avenues for future rational design of TPP inhibitors are proposed and it is hoped that this work will support the development of new treatments for parasitic disease.
Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Environment and Sc
Science, Environment, Engineering and Technology
Full Text

Estudio de caso para optar al grado de Magister en Estrategia Internacional y Política Comercial.
El presente Estudio de Caso tiene como propósito estudiar el rol que tuvieron en Chile los grupos de interés en la negociación del Acuerdo de Asociación Transpacífico (TPP), específicamente en materia de Propiedad Intelectual en Chile. Para ello, se estudiará los objetivos de dichos grupos en la posición de Chile, para luego contrastar ambas posiciones, en este caso la posición asumida por Chile y la postura establecida de los grupos de interés y concluir.

Controlled release systems aim at achieving a predictable and reproducible drug release over a desired time period. These systems allow reduced dosing frequency, constant drug levels in the blood, increased patient compliance and decreased adverse effects. In a recent study, Chitosan beads, containing N-trimethyl Chitosan chloride, have shown a potential in the delivery of rifampicin. However, because of inadequate amounts of rifampicin released over 24 hours, incorporation of other pharmaceutical excipients to increase the swelling behaviour of the beads to improve drug release, was considered in this study. Chitosan beads were prepared through ionotropic gelation with tripolyphosphate (TPP) as a crosslinking agent. To increase the porosity if the Chitosan beads Explotab®, Ac-Di-Sol® and vitamin C were added individually to Chitosan solutions at concentrations of 0.1, 0.25 and 0.5 % w/v before adding the mixture to the TPP solution. Swelling and morphology studies were used in the evaluation of the different formulations. The swelling and morphology results were then used to select a set of combination and concentrations of two excipients sand then prepare and characterise beads containing two combinations. The combination formulations and formulations containing single excipients were then loaded with rifampicin. Pure chitosan beads exhibited a higher drug loading capacity (67.49 %) compared to the lowest loading capacity of 41.61 % exhibited by chitosan beads containing a combination of Explotab®, Ac-Di-Sol®.For all the other formulations the drug loading capacity ranged within 48 and 63 %. These formulations were used for dissolution studies over a period of 6 hours at pH 5.60 and 7.40. The dissolution results showed that no chitosan has dissolved at both pH values. A significant amount of rifampicin was, however, released from the beads, especially at pH 7.40. chitosan beads containing vitamin C also exhibited high rifampicin release (48.34 ± 1.00) %) at pH 5.60 compared to the other formulations and this makes vitamin C a potential excipient for enhanced drug release over a wide pH range (both acidic and alkalinic). However, further studies are necessary to optimise the preparation method to minimise drug loss during loading and to improve the drug loading capacity of the beads.
Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2005.

In controlled release applications a drug is molecularly dispersed in a polymer phase. In the presence of a thermodynamically compatible solvent, swelling occurs and the polymer releases its content to the surrounding medium. The rate of the drug release can be controlled by interfering with the swelling rate of the beads or by influencing diffusion through the viscosity of the polymer. Beads that contain chitosan were prepared through the ionotropic gelation method where tripolyphosphate (TPP) was used as the crosslinking agent. Beads that consisted of 3% w/v isoniazid (lNH) and 5% w/v chitosan were prepared in a 5% w/v TPP solution (pH 8.7) as the primary beads. To improve the drug loading of chitosan isoniazid beads (ClB) the TPP concentration, pH of the TPP solution and the INH concentrations were altered for maximum drug loading. To increase the porosity of the beads of chitosan beads Explotab® (EXPL), Ac-Di-Sol® (ADS) and Vitamin C (VC) were added individually to chitosan solutions at concentrations of 0.1, 0.25 and 0.5% w/v before adding the mixture to the TPP solution. Morphology, swelling and drug loading studies were used to evaluate the different formulations. After these excipients were added individually they were also added in combinations of two excipients respectively and characterised. From the results of the drug loading studies the beads that contained only chitosan and isoniazid showed a percentage drug loading of (43.92%) which is the best of all the beads that were analyzed. The multi excipient combination of Ac-Di-Sol® and Explotab® showed the best swelling capability at both pH levels. Dissolution studies were conducted on all the formu lations over a period of 6 hours (360 minutes) at pH 5.6 and pH 7.4. From the dissolution results it were clear that no chitosan dissolved at both pH values. The dissolution of single pharmaceutical excipient (SPE) and multi pharmaceutical excipient (MPE) formulations can be arranged in the following order: VC/ADS < VC < ADS/EXPL < ADS < VC/EXPL < CIB < EXPL. Explotab® is a potential excipient for enhanced drug release over a wide pH range.
Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2007.

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The purpose of this study is to examine the effects of the possibility of Brazil integrate the main agreements of the Asian region, the Trans-Pacific Partnership (TPP) and the Regional Comprehensive Economic Partnership (RCEP). A computable general equilibrium model is employ to simulate scenarios on various agreements, which will make it possible to identify the potential impacts and opportunities for Brazilian agribusiness. The impact on exports, imports and production of the agribusiness segments will have the emphasis, through scenarios to reduce trade barriers between countries participating in the agreements. Faced with difficulties in advancing multilateral agreements, the protectionist position of the United States, and the difficulties of opening up the European market, we must consider taking up the potential space that these countries will leave in trade relations with other nations and economic blocs. The results indicate that Brazilian agribusiness; GDP and Welfare are more benefited through participation in the agreements than to stay away from them. Integrating simultaneously in TPP and RCEP is the scenario that most favours Brazilian agribusiness. Joining the RCEP brings the best effects on welfare The results also indicate that RCEP is the hypothetical scenario most beneficial for GDP.
O presente estudo tem como objetivo examinar os efeitos sobre o Brasil da formação dos principais acordos da região asiática, o Trans-Pacific Partnership (TPP) e o Regional Comprehensive Economic Partnership (RCEP). Diante das dificuldades no avanço de acordos multilaterais, a posição protecionista dos EUA, e as dificuldades para uma maior abertura do mercado europeu, é preciso considerar ocupar o espaço potencial que estes países deixarão nas relações comerciais com outras nações e blocos econômicos. O modelo de equilíbrio geral computável Global Trade Analysis Project (GTAP) foi utilizado para simulação de cenários alternativos, que consideram a formação desses acordos com e sem a participação do Brasil nos mesmos. As simulações permitem identificar os potenciais impactos e oportunidades para a economia brasileira, em especial, para o agronegócio do país. Os cenários são simulados por meio de eliminação de barreiras comerciais tarifárias entre países participantes dos acordos. Os resultados apontam que o agronegócio brasileiro, PIB e Bem-estar serão mais beneficiados através da participação nos acordos do que a permanecer afastado dos mesmos. Integrar-se simultaneamente no TPP e RCEP é o cenário que mais favorece o agronegócio brasileiro. Já associar-se ao RCEP traz os melhores efeitos ao Bem-estar. Os resultados ainda indicam que RCEP é o cenário hipotético mais benéfico para PIB.

I januari 2018 kommer det nuvarande EU-direktivet PSD att ersättas av det nya betaltjänstdirektivet Payment Services Directive 2 (PSD2). Motiven bakom direktivets införande är bland andra att bidra till en förenkling för tredjepartsaktörer att inträda betaltjänstmarknaden samt öka valmöjligheten för konsumenten. Idag domineras betaltjänstmarknaden främst av banker, något som direktivet utformats för att motverka. Syftet med denna studie är att undersöka hur väl några av direktivets motiv stämmer överens med aktörernas uppfattning av direktivets påverkan samt även undersöka vilka möjligheter och utmaningar banker och tredjepartsaktörer ser att det nya direktivet innebär för dem och marknaden. Uppsatsen är genomförd som en fallstudie där semistrukturerade intervjuer med banker och tredjepartsaktörer varit den främsta datainsamlingsmetodiken. Fallstudien visade att aktörernas uppfattning av direktivet till stora delar stämmer bra överens med motiven för direktivet. Samtliga aktörer har en förhållandevis positiv bild av direktivet och ser en mängd olika möjligheter med direktivet. Samarbetet mellan banker och tredjepartsaktörer ses som en av de större möjligheterna. Utmaningarna som aktörerna står inför är varierande beroende på typ av aktör. Studien visade att det finns en del utmaningar som kan komma att begränsa antalet nya aktörer på marknaden. Samtliga möjligheter och utmaningar presenteras i fallstudiens sjätte avsnitt.
In January 2018, the current EU directive PSD will be replaced by the new Payment Services Directive 2 (PSD2). The motives behind the implementation of the directive are, inter alia, to help simplify third party providers entering the payment service market and increasing consumer choice. Today, the payment service market is uppermost dominated by banks, something that the directive is designed to counteract. The purpose of this study is to investigate how well some of the motives of the directive are in line with the actors' perception of the impact of the directive, as well as investigate what opportunities and challenges banks and third party providers see that the new directive implies for them and the market. The essay was conducted as a case study, where semistructured interviews with banks and third party players were the primary data collection methodology. The case study showed that the actors' perception of the directive largely complies with the motives for the directive. All actors have a relatively positive view of the directive and see a wide range of possibilities with the directive. Cooperation between banks and third parties is seen as one of the major opportunities. The challenges that the stakeholders face are varied depending on the type of actor they represent. The study showed that there are some challenges that may limit the number of new players in the market. All possibilities and challenges are presented in the sixth section of the case study.

P68 RNA helicase is a RNA helicase and an ATPase belonging to the DEAD-box family. It is important for the growth of normal cells, and is implicated in diverse functions ranging from pre-mRNA splicing, transcriptional activation to cell proliferation, and early organ development. The protein is documented to be phosphorylated at several amino-acid residues. It was previously demonstrated in several cancer cell-lines that p68 gets phosphorylated at threonine residues during treatments with TNF-α and TRAIL. In this study, the role of threonine phosphorylation of p68 under the treatment of anti-cancer drug, oxaliplatin in the colon cancer cells is characterized. Oxaliplatin treatment activates p38 MAP-kinase, which subsequently phosphorylates p68 at T564 and/or T446. P68 phosphorylation, at least partially, influences the role of the drug on apoptosis induction. This study shows an important mechanism of action of the anti-cancer drug which could be used for improving cancer treatment. This study also shows that p68 is an important transcriptional regulator regulating transcription of the cytoskeletal gene TPPP/p25. Previous analyses revealed that p68 RNA helicase could regulate expression of genes responsible for controlling stability and dynamics of different cytoskeletons. P68 is found to regulate TPPP/p25 gene transcription by associating with the TPPP/p25 gene promoter. Expression of TPPP/p25 plays an important role in cellular differentiation while the involvement of p68 in the regulation of TPPP/p25 expression is an important event for neurite outgrowth. Loss of TPPP expression contributes to the development and progression of gliomas. Thus, our studies further enhance our understanding of the multiple cellular functions of p68 and its regulation of the cellular processes.

Memoria (licenciado en ciencias jurídicas y sociales)
No autorizada por el autor para ser publicada a texto completo
El presente trabajo busca entregar una aproximación al concepto de Coherencia Regulatoria de conformidad al uso que se le ha dado en el contexto del Derecho Internacional Económico, especialmente en procesos de gobernanza internacional y de negociación de acuerdos internacionales de comercio. Para lograr este objetivo, el trabajo realiza un análisis de las fuentes que identifica como las raíces de la Coherencia Regulatoria como una nueva disciplina del derecho comercial económico- Asimismo, identifica los elementos que estima son esenciales de esta disciplina para finalmente dar paso a una definición del concepto y un análisis sobre el devenir de la misma en el Derecho Internacional Económico.

Marknaden för betaltjänster har ökat avsevärt de senaste åren i och med teknikens utveckling och konsumenters ändrade betalningsvanor. Betalningarna har gått från att domineras av kontanter till att idag bestå av kortbetalningar och moderna betaltjänstlösningar via t.ex. mobiltelefoner. I takt med att e-handeln har expanderat och nya leverantörer av betaltjänster har trätt in på marknaden har behovet av ett gemensamt regelverk på EU-nivå för betaltjänster ökat, detta för att samtliga betalningar som sker inom EU ska vara lika effektiva och säkra som nationella betalningar.   Den 13 januari 2018 trädde det andra betaltjänstdirektivet (PSD2) ikraft, vilket syftar till att harmonisera marknaden för elektroniska betalningar och skapa bättre förutsättningar för innovativa, säkra och effektiva betalningar inom EU. I och med införandet av PSD2 utvidgades definitionen av betaltjänster till att innefatta betalningsinitieringstjänster och kontoinformationstjänster, vilka är tredjepartsleverantörer och fungerar som ett mellanled mellan en bank och slutkunden på betaltjänstmarknaden. Marknaden för tredjepartsleverantörer har hittills varit oreglerad, men omfattas nu av PSD2:s tillämpningsområde, vilket gör att tredjepartsleverantörerna kan få tillgång till bankernas kundinformation och kunddata genom öppna applikationsprogrammeringsgränssnitt. Under våren 2018 kommer en ny dataskyddsförordning att träda i kraft, vilken ämnar till att ge ett ökat skydd för den personliga integriteten genom att införa striktare regler angående behandling av personuppgifter.   Uppsatsen fokuserar på tredjepartsleverantörer och hur de påverkas av de nya regelverken och om innovationsmöjligheterna för nya betaltjänster kommer att främjas genom införandet av PSD2. För att kunna se hur tredjepartsleverantörerna påverkas av regelverken kommer uppsatsen fokusera på behandlingen av person- och kontouppgifter för att avgöra om bestämmelserna i PSD2 är förenliga med dataskyddsförordningen. Av uppsatsens resultat går det att utläsa att innovationen av nya betaltjänster fortsättningsvis torde främjas av de nya reglerna i PSD2 och att utvecklingen torde ske i en snabbare takt än tidigare. Det går även att utläsa att reglerna i de båda regelverken till viss del stämmer överens, men även att det finns bestämmelser som är motstridiga.

Doutoramento em Biologia
Antifouling (AF) systems are used worldwide to prevent biofouling, a natural phenomenon characterized by the attachment and growth of living organisms onto submerged surfaces. Biofouling may lead to elevated economic losses not only due to the deterioration of submerged structures but also, in the case of vessels, to the increase of frictional drag that ultimately results in the rise of fuel consumption and the reduction of the vessel´s operational time. The hulls chemical protection against this phenomenon has been a common practice in the naval industry but the leaching of biocides from AF systems into the aquatic environment has frequently caused severe adverse ecological impacts. Therefore, it is critical to search for more environment-friendly AF biocides, valuing the compromise of having a good AF performance to target organisms and the lowest ecological impact. Organotin compounds (OTs), especially tributyltin (TBT) and to a lesser extent triphenyltin (TPT), have been used as biocides in AF paints from the 1960's until their ban in 2008. As a consequence, a number of other compounds emerged as substitutes. There was a return to predominantly copper based AF paints with one or more booster biocides added to the formulations to achieve a maximum performance. These alternatives comprised diuron, irgarol 1051, zinc pyrithione, tolylfluanid and dichlofluanid among others. However, some of them have also been banned or phased out from the market due to their toxic effects to aquatic organisms. One objective of the present thesis was to assess the current levels of these AF biocides along the Portuguese coast. For this purpose, a survey was performed in 2011 where both sediments and tissue samples from the mediterranean mussel Mytillus galloprovincialis were collected and analysed to determine the extent of the above mentioned biocides contamination. It was also assessed the imposex levels in the gastropod Nucella lapillus as a proxy to evaluate the status of TBT pollution. The tissues of this bioindicator were also analysed for OTs due to the proven cause-effect relationship between imposex and TBT/TPT body burden. The results reveal that despite the OT global ban in 2008, TBT was still ubiquitous being measured in all assessed sediment samples (3.0 – 850 ng Sn g-1 dry weight (dw)) and in both mussel (1.1 – 420 ng Sn g-1 dw) and dogwhelk tissues (1.4 – 30.4 ng Sn g-1 dw). TPT was less abundant as it was detected in approximately 50 % of the samples: concentration in sediments varied between the detection limit (dl) of 0.1 and 43 ng Sn g-1 dw; in mussel tissues ranged between the dl of 0.2 and 14 ng Sn g-1 dw; in dogwhelk tissues varied from the dl of 0.2 to 1.6 ng Sn g-1 dw. The percentage of N. lapillus females affected by imposex (%I), the vas deferens sequence index (VDSI) and the relative penis size index (RPSI) were used to measure the intensity of imposex and varied between 36.7 – 100%, 0.39 – 7.75 and 0 – 1.22, respectively. Sterile females were only found at one site. Despite the TBT ubiquity in the Portuguese coast, with major incidence close to naval harbours, a decreasing temporal trend of organotin pollution has been observed; in fact, the comparison of 2011 results with those from previous years denote an evident decline of TBT contamination of sediments and biota (namely, mussels and dogwhelks) and N. lapillus imposex. This survey also detected Cu, Zn and diuron in both sediments and mussel tissues. Although the metals have natural and wide anthropogenic sources and diuron may also come from pesticide use in agriculture, the results may point towards their ubiquitous use in AF-paints in a recent past. In the sediments, Cu, Zn and diuron varied between 1.7 and 240 mg Kg-1 dw, the dl of 10 and 620 mg Kg-1 dw and 7.7 and 67 ng g-1 dw, respectively. In mussel tissues Cu varied between 4 and 11 mg Kg-1 dw, Zn between 94 and 640 mg Kg-1 dw and diuron ranged from the dl of 3 to 20 ng g-1 dw. Seldom it was also detected irgarol - measured in 6 (out of the 13) sampled sediment stations (6.8 – 43 ng g-1 dw) and in 5 (out of the 37) mussel tissue samples (18.7 – 183 ng g- 1 dw) - and its metabolite GS26575 measured in only one sediment sample (41 ng g-1 dw) and varying between 4.1 and 188 ng g-1 dw in 4 (out of 37) mussel tissue samples. Tolylfluanid was only measured in 3 (out of 13) sediment samples (9.4 – 21.9 ng g-1 dw) and in 2 (out of 37) mussel tissues samples (5.3 and 26.8 ng g-1 dw). Dichlofluanid content in mussel tissues varied between 2.3 - 160 ng g-1 dw occurring in 5 (out of 37) stations whilst in sediments was always below the detection limit. Nonetheless, contrasting with TBT spatial distribution, no specific pattern could be clearly recognized on the distribution of these AF biocides. With the implementation of the new Biocidal Product Regulation (EU Regulation 528/2012), emerging substances aiming to present a high AF potential to target organisms and a low environmental impact arose. A low toxicity to non-target species as well as a low tendency to bioaccumulate and a rapid transformation to less toxic products are required characteristics of environment-friendly biocides. For this thesis a bibliographic research was carried out in order to select emerging biocides with promising properties. Three biocides were chosen: tralopyril, triphenylborane pyridine (TPBP) and capsaicin. Tralopyril is the main active substance of ECONEA®, being marketed as a non-persistent and biodegradable copper-free biocide, effective in controlling fouling by barnacles, hydroids, mussels and polychaetas. TPBP, also known as Borocide®, is an organoborane compound used as a broadspectrum biocide mainly in Japan. Capsaicin is a natural occurring substance, derived from the chili pepper plant commonly used as animal repellent and claimed to improve the paint efficiency. Therefore, most of the work of this thesis comprehended the characterization of some aspects of the PBT (Persistence, Bioaccumulation and Toxicity) criteria of these biocides in order to perform a proper ecological risk assessment. Giving the scarcity of data in the literature, the major objective of this thesis was to gather new data about the toxicity of tralopyril, TPBP and capsaicin to freshwater and marine organisms, in order to provide novel insights regarding the potential impact of these chemicals to aquatic ecosystems. Regarding the marine environment, a study with early life stages of target and non-target species was carried out. It showed that the tested biocides impaired larval development in the mussel M. galloprovincialis (EC50_tralopyril = 3.1 μg L-1 and EC50_capsaicin = 3868 μg L-1) inhibited larval growth in the sea urchin P. lividus (EC50_tralopyril = 3.0 μg L-1 and EC50_capsaicin = 5248 μg L-1) and caused mortality to the copepod T. battagliai (EC50_tralopyril = 0.9 μg L-1, EC50_capsaicin = 1252 μg L-1 and EC50_TPBP = 14 μg L-1) in a dose-dependent way. When comparing the risk posed by these three emerging biocides with TBT, a reference AF substance, in a seawater marina model, it was concluded that the three tested compounds pose less risk than TBT but, nevertheless, tralopyril and TPBP might represent a considerable threat to the marine ecosystems. Capsaicin was described as the least toxic compound, apparently with no risk but also not presenting a high biocide performance. The next step was to characterize the toxicity of tralopyril, TPBP and capsaicin to three freshwater model species: the algae Chlamydomonas reinhardtii, the crustacean Daphnia magna and the fish Danio rerio. The lethal effects of the three biocides were studied for all the aforementioned species whilst sub-lethal effects were only assessed for the algae and zebrafish. Tralopyril was the only biocide that caused mortality to C. reihardhtii (LC50 = 71 μg L-1). In the D. magna acute immobilization test, tralopyril and TPBP revealed similar toxicities but only if the concentrations were mantained constant by means of solution renewal. To the zebrafish, tralopyril was undoubetly the most lethal (LC50 = 5.0 μg L-1) followed by TPBP (LC50 = 447.5 μg L-1). Capsaicin did not exert any lethal effects to any of the species tested. Regarding sub-lethal toxicity, both tralopyril and TPBP caused significant effects on C. reihardhtii effective quantum yield and ATP content, however TPBP was much less toxic. Concerning zebrafish, TPBP inhibited the swim bladder inflation, caused heart edema, reduced the blood flow and, at the highest concentrations, led to a diminish of the heart beat rate, whilst tralopyril only caused an inhibition of the swim bladder inflation though at much lower concentrations. Capsaicin caused an increase on the zebrafish embryo heart beat rate although not in a doseresponsive way. The results herein provided data on the effects of the three emerging biocides on freshwater ecosystems but also, as these species belong to different trophic levels, it helped to reduce the assessment factor used in risk assessment, decreasing the uncertainty of such prediction. Thus, the risk assessment performed for a freshwater marina corroborated previous investigations where capsaicin was identified as an environment-friendly compound whilst tralopyril and TPBP were identified as possible threats to the ecossystem. In order to have some insights into the mode of action of the two most toxic compounds referred above - tralopyril and TPBP - further investigations using a differential proteomic analysis were carried out. Sub-lethal tralopyril and TPBP concentrations regulated both general stress-related and compoundspecific proteins on the zebrafish embryo proteome. The common protein regulations between compounds are thought to be stress-related changes and comprehended the altered expression of proteins involved in energy metabolism, eye structure and in cell differentiation processes. Sub-lethal tralopyril exposure specifically upregulated six other proteins involved in energy metabolism, cytoskeleton, cell division and mRNA splicing whilst exposure to TPBP comprised the regulation of three proteins belonging to the cytoskeleton, cell growth and protein folding. Moreover, calculations on the toxic ratio of both compounds identified TPBP as a baseline toxicant whilst tralopyril was found to have a specific toxicity mode of action. As tralopyril became an important candidate to be used in European waters (due to its inclusion on the Biocidal Product Regulation) and also because this biocide revealed the highest and more specific overal toxicity, additional studies were undertaken to better understand the persistence and bioaccumulation potential of this compound. For that, it was essential to develop a sensitive analytical method to measure tralopyril in aqueous matrices. Therefore, a targeted analytical LC-MS/MS method was established to quantify tralopyril in DMSO (the solvent used in all studies portrayed in this thesis) and water samples (natural river and seawater, and medium used for zebrafish exposures - E3 medium). The limits of quantitation achieved for the different media are sufficiently low to detect tralopyril without a preconcentration step (0.05 μg L-1 for river water and 0.025 μg L-1 for the other media analysed). Estimated tralopyril half-lives were 6.1 h for seawater, 8.1 h for river water and 7.4 h for E3 medium at 18º C. In order to study the bioaccumulation potential, tralopyril concentrations were measured in the whole tissues of M. galloprovincialis following acute and chronic exposure, and after a 10-day depuration period. This biocide rapidly accumulated in the mussel tissues, reaching the steady-state condition within 13 days. Nevertheless, mussels seemed to be able to eliminate the compound since 10 days of depuration resulted in 80% elimination of the accumulated biocide. In order to further understand the sub-lethal toxicity of tralopyril to M. galloprovincialis and the possible mode of action, differential proteomics analysis was performed on the gill proteome of this species following acute and chronic exposure, and after a 10-day depuration period. Interestingly, not only tralopyril but also DMSO (used as solvent) significantly modulated the protein expression in mussel gils after acute and chronic exposure. Altogether, 46 proteins involved in bioenergetics, immune system, active efflux and oxidative stress were found to be regulated in the different exposure scenarios. Notably, after the depuration period, alterations of several proteins were still observed possibly reflecting either the continued effect or the incomplete elimination of this chemical. In conclusion, this thesis shows a change in the paradigm regarding AFbiocides, i.e., moving from older generation biocides with high ecological risk, to new ones that should desirably present low persistence and no impact to nontarget species, a difficult task that involves perseverance and hard work.
Os sistemas anti-vegetativos (AV) são usados mundialmente para evitar a incrustação biológica, um fenómeno natural caracterizado pela fixação e crescimento de organismos vivos em superfícies submersas. A bioincrustação pode levar a elevadas perdas económicas, não só devido à deterioração de estruturas submersas, mas também, no caso de navios, ao aumento da resistência à deslocação que resulta num acréscimo do consumo de combustível e na redução do tempo de vida operacional do navio. A proteção química dos cascos dos navios, contra este fenómeno, tem sido uma prática comum na indústria naval, mas a lixiviação de biocidas dos sistemas AV no meio aquático tem frequentemente causado impactos ecológicos adversos graves. Portanto, é fundamental procurar biocidas AV, mais amigos do ambiente, valorizando o compromisso entre ter um bom desempenho AV para atingir organismos alvo mas com um menor impacto ecológico. Os compostos organoestânicos (OTS), especialmente o tributil-estanho (TBT) e, em menor medida o trifenil-estanho (TPT), têm sido utilizados como biocidas em tintas AV desde a década de 1960 até à sua proibição em 2008. Como consequência, uma série de outros compostos surgiram como substitutos. Houve um retorno predominante ao uso de tintas AV à base de cobre com um ou mais biocidas de reforço adicionados às formulações, para alcançar um desempenho máximo. Estas alternativas incluíram diuron, Irgarol 1051, piritiona de zinco, tolilfluanida e diclofluanida entre outros. No entanto, alguns deles também foram proibidos ou retirados do mercado devido aos seus efeitos tóxicos para os organismos aquáticos. Um dos objectivos da presente tese foi avaliar os níveis destes biocidas AV presentes ao longo da costa Portuguesa. Com esta finalidade, foi realizado um estudo científico, em 2011, onde foram recolhidas e analisadas amostras de sedimentos e de tecido de mexilhão (Mytillus galloprovincialis) para determinar a extensão da contaminação pelos biocidas acima mencionados. Foram também avaliados os níveis de imposex no gastrópode Nucella lapillus como forma de verificar o estado da poluição por TBT. Os tecidos deste bioindicador foram somente analisados para o conteúdo de organoestânicos devido à relação causa-efeito já comprovada entre imposex e o conteúdo de TBT / TPT nos tecidos. Os resultados revelaram que, apesar da proibição mundial de OTs, em 2008, o TBT continua disseminado por toda a costa, sendo detetado em todas as amostras de sedimento (3.0 - 850 ng Sn g-1 peso seco (ps)) e também em amostras de tecidos de mexilhão (1.1 - 420 ng Sn g-1 ps) e do gastrópode N. lapillus (1.4 - 30.4 ng Sn g-1 ps). O TPT é menos abundante, uma vez que apenas foi detectado em cerca de 50% das amostras: a concentração nos sedimentos variou entre o limite de detecção (ld) de 0.1 e 43 ng Sn g-1 ps; a concentração nos tecidos de mexilhão variaram entre o ld de 0.2 e 14 ng Sn g-1 ps; a concentração em tecidos do gastrópode variaram entre o ld de 0.2 e 1.6 ng Sn g-1 ps. A percentagem de fêmeas do gastrópode N. lapillus afectadas por imposex (% I), o índice de sequência de vaso deferente (VDSI) e o índice de tamanho relativo do pénis (RPSI) foram usadas para medir a intensidade do imposex e variaram entre 36.7 - 100%, 0.39 - 7.75 e 0 - 1.22, respectivamente. Fêmeas estéreis foram encontradas apenas numa estação de amostragem. Apesar da ubiquidade do TBT no litoral Português, com maior incidência perto de portos navais, foi observada uma tendência temporal decrescente da poluição por organoestanhos; efetivamente, a comparação dos resultados de 2011 com os de anos anteriores denotam uma diminuição evidente da contaminação por TBT não só nos sedimentos e biota (tanto em tecidos de mexilhão como de gastrópodes) mas também no imposex de N. lapillus. Nesta pesquisa também foi detectada a presença de Cu, Zn e diuron em ambas amostras de sedimento e tecidos de mexilhão. Embora os metais possam provir de várias fontes, tanto naturais como antropogénicas, e o diuron possa advir da utilização de pesticidas na agricultura, estes resultados sugerem o uso ubíquo destes biocidas em tintas AV num passado recente. Nos sedimentos, Cu, Zn e diuron variaram entre 1.7 e 240 mg kg-1 ps, entre o ld de 10 e 620 mg kg-1 ps e 7.7 e 67 ng g-1 ps, respectivamente. Em tecidos de mexilhão o Cu variou entre 4 e 11 mg kg-1 ps, Zn entre 94 e 640 mg kg-1 ps e diuron variou desde o ld de 3 a 20 ng g-1 ps. Raramente foram ainda detectados Irgarol – medido em 6 (das 13) estações de sedimentos amostrados (6.8 - 43 ng g-1 ps) e em 5 (das 37) amostras de tecido de mexilhão (18.7 - 183 ng g-1 ps) – e o seu metabolito GS26575 medido em apenas uma amostra de sedimento (41 ng g-1 ps) e variando entre 4.1 e 188 ng g-1 ps em 4 (das 37) amostras de tecido de mexilhão. Tolilfluanida só foi medido em 3 (de 13) amostras de sedimentos (9.4 - 21.9 ng g-1 ps) e em 2 (de 37) amostras de tecido de mexilhão (5.3 e 26.8 ng g-1 ps). O conteúdo de diclofluanida em tecidos de mexilhão variaram entre 2.3 e 160 ng g-1 ps ocorrendo em 5 (de um total de 37) estações, enquanto nos sedimentos esteve sempre abaixo do limite de detecção. No entanto, contrariamente à evidente distribuição espacial do TBT, a distribuição destes biocidas na costa portuguesa não apresentou um padrão específico. Com a implementação do novo Regulamento dos Produtos Biocidas (Regulamento da UE 528/2012), surgiram algumas substâncias emergentes cujo propósito é apresentar um elevado potencial AV para organismos alvo e baixo impacto ambiental. A baixa toxicidade para espécies não-alvo, bem como uma baixa tendência de bioacumulação e uma rápida transformação para produtos menos tóxicos são características necessárias de biocidas mais amigos do ambiente. Para esta tese foi realizada uma pesquisa bibliográfica, a fim de selecionar compostos emergentes com propriedades promissoras. Três biocidas foram escolhidos: tralopyril, trifenilborano piridina (TPBP) e capsaicina. Tralopyril é a principal substância ativa do produto ECONEA®, comercializado como um biocida livre de cobre, não persistente e biodegradável, eficaz no controle da proliferação de cracas, hidrozoários, mexilhões e poliquetas. TPBP, também conhecido como Borocide®, é um composto organoborano usado como biocida de largo espectro, principalmente, no Japão. A capsaicina é uma substância natural, derivada da planta da pimenta utilizada como repelente de animais e que adicionada às tintas AVs alegadamente melhora a sua eficácia. Assim, a maior parte do trabalho desta tese compreendeu a caracterização de alguns aspectos dos critérios PBT (Persistência, Bioacumulação e Toxicidade) destes biocidas, a fim de realizar uma avaliação adequada do risco ecológico. Devido à escassez de dados na literatura, o principal objetivo desta tese foi reunir novos dados sobre a toxicidade do tralopyril, TPBP e capsaicina tanto em organismos marinhos como de água doce, a fim de proporcionar novos conhecimentos sobre o potencial impacto desses produtos químicos nos ecossistemas aquáticos. Relativamente ao ambiente marinho, foi realizado um estudo com estádios iniciais de vida de espécies-alvo e não-alvo. Observou-se que os biocidas testados comprometeram o desenvolvimento larvar do mexilhão M. galloprovincialis (EC50_tralopyril = 3.1 μg L-1 e EC50_capsaicina = 3868 μg L-1) inibiram o crescimento larvar do ouriço do mar P. lividus (EC50_tralopyril = 3,0 μg L-1 e EC50_capsaicina = 5248 μg L-1) e causaram mortalidade no copépode T. battagliai (EC50_tralopyril = 0,9 μg L-1, EC50_capsaicina = 1252 μg L-1 e EC50_TPBP = 14 μg L-1) em função da dose usada. Ao comparar o risco ambiental apresentado pelos três biocidas emergentes com o do TBT, uma substância AV de referência, num modelo de marina de água salgada, concluiu-se que os três compostos testados apresentam menor risco que o TBT. No entanto, tanto o tralopyril como o TPBP podem representar uma ameaça considerável para os ecossistemas marinhos. A capsaicina parece ser como o composto menos tóxico, aparentemente, sem risco mas também sem um alto desempenho biocida. O passo seguinte foi caracterizar a toxicidade do tralopyril, TPBP e capsaicina em três espécies modelo de água doce: a alga Chlamydomonas reinhardtii, o crustáceo Daphnia magna e peixe-zebra Danio rerio. Os efeitos letais dos três biocidas foram estudados para todas as espécies acima mencionadas, enquanto que os efeitos sub- letais foram avaliados apenas para as algas e peixe-zebra. Tralopyril foi o único biocida que causou mortalidade na alga C. reihardhtii (LC50 = 71 μg L-1). No teste agudo de imobilização da D. magna, tralopyril e TPBP revelaram toxicidades semelhantes, mas somente se as concentrações fossem mantidas constantes por meio de renovação da solução. Para o peixe-zebra, tralopyril foi sem dúvida o composto mais letal (LC50 = 5.0 μg L-1) seguido pelo TPBP (LC50 = 447.5 μg L-1). A capsaicina não exerceu quaisquer efeitos letais em nenhuma das espécies testadas. Em relação à toxicidade sub-letal, tanto o tralopyril como o TPBP causaram efeitos significativos no rendimento quântico efetivo e no conteúdo de ATP em C. reihardhtii, no entanto o TPBP apresentou uma toxicidade bastante mais baixa. Em relação ao peixe-zebra, o TPBP inibiu a inflação de bexiga natatória, causou edema no coração, reduziu o fluxo sanguíneo e, nas concentrações mais elevadas, levou a uma diminuição da taxa de batimento cardíaco, enquanto que o tralopyril causou apenas uma inibição da inflação de bexiga natatória embora numa concentração bastante menor. A capsaicina causou um aumento na taxa de batimentos cardíacos do embrião de peixe-zebra, embora de uma forma não dependente da concentração do composto. Os resultados aqui descritos não só proporcionam informação sobre os efeitos dos três biocidas emergentes sobre os ecossistemas de água doce, mas também, uma vez que estas espécies pertencem a níveis tróficos diferentes, ajudou a reduzir os factores de avaliação utilizados na avaliação de risco, diminuindo a incerteza de tal previsão. Assim, a avaliação de risco realizada para uma marina de água doce corroborou investigações anteriores, em que a capsaicina foi identificada como um composto amigo do ambiente, enquanto que o tralopyril e o TPBP foram identificados como possíveis ameaças ao ecossistema. Com a finalidade de compreender o modo de ação dos dois compostos mais tóxicos, acima referidos - tralopyril e TPBP - novas investigações foram efectuadas usando uma analise proteómica diferencial. Concentrações subletais de tralopyril e TPBP regularam tanto proteínas relacionadas com o stress geral do organismo, como também outras proteínas mais especificas da ação do composto, no proteoma do embrião de peixe-zebra. Pensa-se que a regulação de proteínas comuns entre compostos possa ser relacionada com o stress e abrangeram a alteração de proteínas envolvidas no metabolismo energético, estrutura do olho e processos de diferenciação celular. A exposição a concentrações sub-letais de tralopyril regularam positivamente seis proteínas específicas envolvidas no metabolismo da energia, do citoesqueleto, da divisão celular e no splicing do mRNA, enquanto que a exposição a TPBP levou à regulação de três proteínas pertencentes ao citoesqueleto, crescimento celular e protein folding. Foram ainda efectuados cálculos sobre o Toxic Ratio de ambos os compostos que identificaram o TPBP como um químico responsável por uma toxicidade mais geral, enquanto que o tralopyril parece ter um modo de ação mais específico.Uma vez que o tralopyril se tornou num candidato importante a ser utilizado em águas europeias (devido à sua inclusão no Regulamento dos Produtos Biocida) e também porque este composto revelou a mais alta e específica toxicidade, de entre os 3 biocidas, foram realizados estudos adicionais para compreender melhor a sua persistência e potencial de bioacumulação. Para isso, foi essencial desenvolver um método analítico sensível para medir este composto em matrizes aquosas. Assim, um método analítico por LC-MS/MS foi estabelecido para quantificar tralopyril em DMSO (o solvente utilizado em todos os estudos realizados nesta tese) e em amostras aquosas (águas naturais de rio e do mar, bem como o meio utilizado nas exposições de embriões de peixezebra - Medio E3). Os limites de quantificação do tralopyril nos vários meios utilizados foram suficientemente baixos para detectar tralopyril sem um passo de pré-concentração (0.05 μg L-1 para águas do rio e 0.025 μg L-1 para os outros meios de analisados). O tempo de meia-vida estimado para este composto foi de 6.1 h na água do mar, 8.1 h na água de rio e 7.4 h no meio E3 a 18º C. A fim de estudar o potencial de bioacumulação, foram medidas as concentrações de tralopyril em tecidos de M. galloprovincialis após exposição aguda e crónica, e após um período de depuração de 10 dias. Este biocida acumulou rapidamente nos tecidos de mexilhão, atingindo o estado estacionário em 13 dias. No entanto, pensa-se que os animais sejam capazes de eliminar o composto uma vez que 10 dias de depuração resultaram na eliminação de 80% do biocida acumulado. Com o objectivo de melhor compreender a toxicidade sub-letal do tralopyril em M. galloprovincialis e o modo de ação deste composto, foi realizada uma análise proteómica diferencial no proteoma das brânquias de organismos desta espécie após exposições aguda e crónica e depois de um período de depuração de 10 dias. Curiosamente, não só o tralopyril mas também o DMSO (utilizado como solvente), modularam significativamente a expressão de proteínas nas brânquias de mexilhão após exposições aguda e crónica. No total, 46 proteínas envolvidas na bioenergética, no sistema imunológico, active efflux e no stress oxidativo foram reguladas nos diferentes cenários de exposição. Alterações de várias proteínas foram ainda observadas, depois do período de depuração, possivelmente refletindo quer o efeito contínuo do tralopyril ou da sua eliminação incompleta. Em conclusão, este trabalho mostra uma mudança de paradigma em relação aos biocidas AV, isto é, há uma passagem do uso de biocidas mais antigos com alto risco ecológico, para biocidas mais novos que devem, desejavelmente, apresentar uma baixa persistência e nenhum impacto para as espécies não alvo, uma tarefa difícil que envolve perseverança e trabalho árduo.

Contents: Chitosan -- Controlled drug delivery -- Indomethacin -- Inotropic gelation -- Tripolyphosphate (TPP) -- Explotab® -- Ac-Di-Sol® -- Vitamin C
Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2007.

Även om marknaden för finansiella tjänster digitaliseras i en allt högre takt finns det fortfarandeinträdesbarriärer för nya aktörer som vill utveckla betal- och kontotjänster för konsumenter. Ettav dessa hinder är att infrastrukturen som används för tjänsterna ägs och förvaltas av deetablerade aktörerna vilket försvårar för en fri konkurrens. Som ett led i att bland annat öppnaupp den europeiska finansiella tjänstesektorn och främja innovation har EU därför infört ettandra betaltjänstdirekt (PSD2) som trädde i kraft under 2018. Direktivet omfattar etableradebanker och finansbolag och tvingar dem att exponera betaltjänster och kontoinformation tilltredjepartsleverantörer när kunden gett sitt medgivande. Införandet av PSD2 kommer förändraspelplanen för både etablerade och nya aktörer när befintliga affärsmodeller utmanas i takt medatt kunderna själva väljer finansiella tjänster efter tycke och smak. Denna kandidatuppsats syftar till att öka förståelsen för hur etablerade banker och finansbolagförhåller sig till möjligheterna och utmaningarna med att anpassa sina verksamheter i enlighetmed PSD2. Därtill är syftet att undersöka huruvida alternativet att inte ta upp kampen med nyaaktörer om de kundnära tjänsterna är en möjlig överlevnadsstrategi för de etablerade aktörerna.Den kvalitativa studien som ligger till grund för slutsatserna bygger på intervjuer somgenomförts med respondenter från två etablerade aktörer samt en ny aktör på den svenskabankmarknaden. Principerna för kvalitativ innehållsanalys har tillämpats vid strukturering ochanalys av intervjuerna. Resultatet visar att PSD2 även förväntas ge etablerade aktörer nya möjligheter attvidareutveckla sina tjänster genom att använda det tekniska ramverket utöver de regulatoriskakrav som direktivet föreskriver. I valet av strategi för PSD2 och de möjliga roller i värdekedjansom erbjuds finns det dock utmaningar med både den mest tillbakalutade och framåtriktademarknadspositionen eftersom dessa ställer krav som är svåra att leva upp till. PSD2 kommeräven medföra fler samarbeten mellan etablerade och nya aktörer som följd av att det finns ettömsesidigt beroende mellan parterna i ambitionen om att leverera den bästa kundupplevelsen.

碩士
國立清華大學
國際專業管理碩士班
106
This research will collect the article about the Trans-Pacific Partnership (TPP) and its benefits, concerns to Vietnam economy. My thesis will explain what TPP is, the causes of economic growth and answering why Vietnam benefits from TPP as well as the concerns when Vietnam becomes the TPP members. I hope my thesis will provide helpful information to whom or organizations care about Vietnam economy after joining TPP. For the foreign companies, I hope you can know what advantages Vietnam can give you when investing in Vietnam, what disadvantages you should know to minimize the loss. For local companies, I hope you know the chance we will encounter in the future as well as the challenges we have to face. For the Vietnam law makers, I hope you will create the policy that help Vietnamese small farmers reduce damage from the international trade and create the policy that use Vietnam advantage efficiently. Key words: Vietnam, Economy, TPP

碩士
義守大學
管理碩博士班
105
Vietnam rice industry has improved massively over the past decades in term of productivity and profitability. Vietnam exports about 6 million tons of rice per year, and it has become one of the biggest rice export country in the world, stand along with Thailand and India. And now, after joining the Trans-Pacific Partnership (TPP) and the upcoming Regional Comprehensive Economic Partnership (RCEP), Vietnam could have a chance to expand its rice market, gain more advantages when competing against India and Thailand. But despite of this, the rice industry of Vietnam still suffer several critical issues such as unstable price and low quality product. Therefore, this research aims to define the advantages and disadvantages for the rice industry of Vietnam in the TPP and RCEP, and identify factors that could enhance the industry. In doing so, can help the industry survive, improve and compete in the TPP and RCEP.

Τα «Συστήματα Αυτόματης Απόδειξης Θεωρημάτων-ΣΑΑΘ» (Automatic Theorem Proving Systems-ATP Systems) είναι συστήματα βασισμένα στη λογική πρώτης τάξεως, τα οποία μπορούν από ένα σύνολο λογικών προτάσεων να συνάγουν την αλήθεια μιας δεδομένης λογικής πρότασης με αυτόματο τρόπο. Η διαδικασία της απόδειξης στα περισσότερα ΣΑΑΘ στηρίζεται στην αρχή της επίλυσης, τον ισχυρότερο κανόνα λογικής εξαγωγής συμπερασμάτων, και την αντίφαση της επίλυσης, μια διαδικασία που εξασφαλίζει την ορθότητα των συμπερασμάτων. Ο ACT-P είναι ένα ΣΑΑΘ που στηρίζεται στην αρχή της επίλυσης και την αντίφαση της επίλυσης, γραμμένο στο εργαλείο GCLISP Developer 5.0 της Gold-Hill, και διαθέτει μια βιβλιοθήκη γνωστών στρατηγικών ελέγχου της διαδικασίας απόδειξης, προσφέροντας τη δυνατότητα στον χρήστη να ορίσει κάθε φορά ένα (κατάλληλο) συνδυασμό στρατηγικών. Στην εργασία αυτή έγινε κατ’ αρχήν μεταφορά του ACT-P σε LispWorks, ένα δυναμικότερο εργαλείο ανάπτυξης εφαρμογών σε Lisp. Επιπλέον, ο χρήστης μέσω του νέου παραθυρικού περιβάλλοντος μπορεί να βλέπει δυο διαφορετικές λύσεις του ίδιου προβλήματος, τη συνοπτική και αναλυτική λύση. Στη συνέχεια, έγινε έλεγχος της καλής λειτουργίας του ACT-P και των στρατηγικών του μέσω δοκιμών με προβλήματα που προέρχονται από την TPTP (Thousands of Problems for Theorem Provers), μια γνωστή βιβλιοθήκη προβλημάτων για ΣΣΑΘ συστήματα στο Διαδίκτυο, και έγιναν οι απαραίτητες διορθώσεις έτσι ώστε να επιλύει προβλήματα από διάφορες κατηγορίες προβλημάτων της βιβλιοθήκης TPTP. Τέλος, έγινε μια μελέτη χρήσης διαφόρων συνδυασμών στρατηγικών ελέγχου για διάφορα προβλήματα της TPTP και εξήχθησαν χρήσιμα συμπεράσματα για την καταλληλότητά τους και την αποδοτικότητά τους σε σχέση με το είδος των προβλημάτων.
Automatic Theorem Proving Systems (ATP Systems) are based on First Order Logic (FOL) and are able to automatically prove the truth of logical sentence. The proof procedure in most ATP Systems uses the resolution principle which is the strongest existing inference rule, and the resolution refutation process which ensure soundeness of the conclusion. The ACT-P is an ATP System which uses the resolution principle and the resolution refutation and it is written in GCLISP Developer 5.0 of Gold-Hill. ACT-P has a library of strategies to control the proof process, and gives users the ability to assign to specify a suitable combination of strategies. In this dissertation a new window based interface is developed for ACTP in Lispworks, which is a powerful tool for developing Lisp applications. The interface gives to the user a more thorough view of the solving process. Moreover, the user can see two different solutions of the problem, the brief and the analytic one. In addition, the functionality and the strategies of ACTP were tested on problems from the TPTP (Thousands of Problems for Theorem Provers) which is a known library of problems for ATP Systems on the web. ACTP has been improved so as to solve problems from various categories of the TPTP library. Finally, different strategy combinations for solving problems from various categories of TPTP library were studied, leading to useful conclusions about the suitability and the performance of the different combinations depending on the problems.

Multilateral trade negotiations within the World Trade Organization have reached a stalemate but there are new trade agreements being currently negotiated, either on bilateral or multinational basis. This thesis deals with two current major trade initiatives, the Trans-Pacific Partnership between the United States and eleven Pacific countries and the Transatlantic Trade and Investment Partnership which includes the United States and the European Union. The thesis uses a comparative analysis to assess economic as well as geopolitical implications of the two trade agreements for the United States. The most apparent geopolitical aspect is the effort of the United States to write the rules of trade for the 21st century before China does so. In regards to economic implications, the thesis works with a concept of intra-industry trade and based on it assesses the possible economic effects on the United States economy, especially in regards to productivity and transactional costs on labor market. Both of the agreements have many critics and their future is not clear. This thesis argues that in certain economic and geopolitical aspects, the Transatlantic Trade and Investment Partnership is more beneficial and strategic for the United States.