Made available in DSpace on 2014-10-09T12:38:37Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T14:05:27Z (GMT). No. of bitstreams: 1 06044.pdf: 6865948 bytes, checksum: a08cf9df31bad7efc0884ad8cc855442 (MD5) / Tese (Doutoramento) / IPEN/T / Instituto de Pesquisas Energeticas e Nucleares - IPEN/CNEN-SP

Made available in DSpace on 2014-10-09T12:35:19Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T14:08:55Z (GMT). No. of bitstreams: 0 / A grande aplicação dos radiofármacos está em medicina nuclear diagnóstica representando 95% dos procedimentos realizados, porém, nos últimos anos, tem crescido consideravelmente a sua aplicação em procedimentos terapêuticos. Os radionuclídeos que emitem particulas ionizantes (α, β e elétrons Auger) são indicados para tratamento de tumores. Tumores malignos são responsáveis por aproximadamente 12% dos óbitos e representam a terceira causa de mortalidade no Brasil. O 188Re é um dos mais atrativos radioisótopos para uma variedade de aplicações terapêuticas em medicina nuclear, oncologia e intervenções cardiológicas, é totalmente favorável e conveniente pelo fato de que ele é livre de carregador e pode ser obtido de forma econômica na forma de um gerador de 188W/188Re, além de possuir uma meia-vida fisica de 16,9 horas e 100% de emissão de radiação β-. A partir da década de 2000 vêm sendo realizadas diversas investigações envolvendo marcações de moléculas com 188Re. Os tumores metastáticos são a forma mais comum de malignidade esquelética. Em casos metastáticos os principais objetivos do tratamento são a prevenção de fraturas patológicas e promover a sobrevida com o máximo de preservação de função permitindo que o paciente mantenha o máximo possível de mobilidade e controle da dor. O objetivo deste trabalho foi realizar a comparação das marcações de diversos fosfonatos (Metileno disfofonato de Sódio MDP, Ácido Etilenodiaminotetrametilenofosfônico EDTMP, e do diclorometilenobifosfonato de sódio - Clodronato) com 188Re para terapia de metastáses ósseas. Fosfonatos são inibidores da reabsorção óssea osteoclástica e são efetivos neste tratamento. As marcações do MDP, EDTMP e Clodronato com 188Re foram otimizadas utilizando como agente redutor o cloreto estanoso (SnCl2 2H2O) e como agente estabilizante o ácido ascórbico. As variáveis estudadas foram massa do ligante, massa do SnCl2.2H2O, massa do ácido ascórbico, tempo, pH e temperatura da reação. Os resultados mostraram que se obteve um excelente rendimento de marcação de 98% para o 188Re-MDP, de 83% para o 188Re-EDTMP e 85% para o 188Re-Clodronato. / Dissertação (Mestrado) / IPEN/D / Instituto de Pesquisas Energeticas e Nucleares - IPEN-CNEN/SP

Submitted by Claudinei Pracidelli (cpracide@ipen.br) on 2016-02-03T12:08:21Z No. of bitstreams: 0 / Made available in DSpace on 2016-02-03T12:08:21Z (GMT). No. of bitstreams: 0 / O crescimento anual no número de procedimentos realizados em Medicina Nuclear se deve em primeiro lugar à vantagem de não serem invasivos. Cerca de 80% dos diagnósticos realizados em Medicina Nuclear utilizam radiofármacos preparados com tecnécio-99m devido a suas características físicas ideais, disponibilidade e baixo custo. Dentre os radiofármacos utilizados para identificar processos de infecção e inflamação estão os leucócitos marcados com tecnécio-99m, considerado o padrão ouro e o citrato de gálio (67 Ga), atualmente comercializado no Brasi. Os leucócitos marcados possuem a desvantagem da técnica laboriosa de marcação nem sempre disponível nos centros de Medicina Nuclear, enquanto o citrato de gálio (67 Ga) não é específico e possui energias desfavoráveis para a dosimetria do paciente e para a aquisição de imagens. Neste cenário, novas moléculas para diagnóstico de focos de infecção têm sido pesquisadas, particularmente envolvendo biomoléculas, como os peptídeos antimicrobianos. Nesta categoria, a Ubiquicidina na forma de um fragmento sintético (UBI 29-41) despertou o interesse de pesquisadores que estudaram a marcação com tecnécio-99m utilizando métodos direto e indireto. Um reagente liofilizado de UBI 29-41descrito na literatura demonstrou eficácia no diagnóstico de focos de infecção utilizando-se imagens cintilográficas, porém o produto não está disponível no Brasil. O objetivo deste trabalho foi estudar a marcação do fragmento de UBI 29-41 com tecnécio-99m por método direto e avaliar a utilização de soluções tampão no procedimento de marcação, de modo a flexibilizar o volume da solução de pertecnetato de sódio a ser utilizado, o que constitui aspecto de ineditismo deste trabalho. O fragmento foi radiomarcado com diferentes volumes de soluções tampão alcalinas (carbonato e fosfato) e a utilização dos tampões em substituição à solução de hidróxido de sódio possibilitou realizar a marcação com diferentes volumes da solução de pertecnetato de sódio, sem comprometimento do rendimento de marcação. Uma formulação liofilizada foi avaliada, demonstrando estabilidade por período de 12 meses, viabilizando a produção rotineira do agente de marcação. Os estudos de biodistribuição das preparações efetuadas com os diferentes tampões demonstraram que os complexos formados apresentam características gerais de biodistribuição semelhantes ao composto padrão descrito na literatura, incluindo rápido clareamento sanguíneo e alta captação renal, condizente com a eliminação do produto por esta via. Entretanto, as preparações estudadas apresentaram captação hepática maior e captação renal menor que o composto padrão. As preparações estudadas captaram no foco de infecção provocado por S.aureus e demonstraram potencial para aplicação clínica no diagnóstico em Medicina Nuclear. Como pré-requisito para a realização de estudos clínicos de um novo composto foi realizado estudo de cito e genotoxicidade, cujos resultados demonstraram a segurança das preparações estudadas. / Tese (Doutorado em Tecnologia Nuclear) / IPEN/T / Instituto de Pesquisas Energeticas e Nucleares - IPEN-CNEN/SP

La galanthamine est un alcaloïde isoquinoléique, utilisé dans le monde entier pour le traitement palliatif de la maladie d’Alzheimer en raison de son pouvoir inhibiteur de l’acétylcholinestérase. Cet alcaloïde est extrait à partir de bulbes d’Amaryllidaceae, Leucojum aestivum, Galanthus nivalis, et Narcissus sp. ou obtenu par synthèse chimique. La difficulté principale de cette dernière réside dans le respect de la configuration des centres d'asymétrie. La culture de tissus in vitro pourrait constituer une alternative intéressante pour obtenir ce composé à haute valeur ajoutée. Le premier objectif de ce projet, vise à améliorer l’accumulation de cet alcaloïde par les biais des biotechnologies. Le second objectif est de rechercher par criblage phytochimique (HPLC, LCMS, GCMS, et HPTLC-MS) de bulbes in vitro et in vivo d’Amaryllidaceae, de nouveaux alcaloïdes biologiquement actifs. Le troisième objectif porte sur l’étude de la voie de biosynthèse en vue de réaliser une synthèse biomimétique de la galanthamine. Nous avons établi des cultures in vitro de 3 espèces d’Amaryllidaceae. La variation des paramètres exogènes a conduit à une accumulation accrue d’alcaloïdes (0,02 à 0,2 % MS). Le criblage phytochimique a conduit à l’identification d’alcaloïdes nouveaux issus des cultures in vitro, n’existant pas in vivo, et présentant un puissant pouvoir inhibiteur de l’acétylcholinestérase (40 à 80 % Inh). L’ajout, de la 4’-Ométhyl-d3-norbelladine aux cultures in vitro a conduit à sa métabolisation en trois types d’alcaloïdes deutérés. Une stimulation de la synthèse et du relargage de la galanthamine native (0,15 % MS et 0,16 % Milieu) a été observée en présence du précurseur deutéré / Galanthamine is an Amaryllidaceae alkaloid used worldwide for the symptomatic treatment of Alzheimer’s disease because of his capacity to inhibit the acetylcholinesterase enzyme. There are two galanthamine sources for medical applications. One is the total synthesis, a complicated process because galanthamine has three asymmetric carbons, requiring stereochemically controlled synthesis. Galanthamine is also extracted from bulbs of some Amaryllidaceae such as Leucojum aestivum, Galanthus nivalis, and Narcissus sp.. The first aim of this work is to improve the accumulation of this alkaloid using biotechnologies. The second aim consists on the phytochemical screening (HPLC, LCMS, GCMS, et HPTLCMS) of in vivo and in vitro Amaryllidaceae bulbs, in order to identify new alkaloids with important pharmacological activities. Finally, the third aim concerns the study of the biosynthesis pathway in order to establish a biomimetic synthesis of galanthamine. Therefore, we established in vitro cultures of three Amaryllidaceae species. The variation of exogenousparameters led to the obtainment of high galanthamine accumulation (0.02 to 0.2 % DW). The phytochemical screening showed new alkaloids in extracts of in vitro cultures, which did not exist in in vivo extracts, and possessing high acetylcholinesterase activity (40 to 80 % Inh). The 4’-O-methyl-d3-norbelladine is incorporated into three different groups ofAmaryllidaceae alkaloids. The addition of the labelled precursor to shoot cultures stimulated the synthesis of native galanthamine (0.15 % DW and 0.16 % Culture medium)

Polyphonic or multiple music instrument detection is a difficult problem compared to detecting single or solo instruments in an audio recording. As music is time series data it be can modelled using sequence learning methods within deep learning. Recently, temporal convolutional networks (TCN) have shown to outperform conventional recurrent neural networks (RNN) on various sequence modelling tasks. Though there have been significant improvements in deep learning methods, data scarcity becomes a problem in training large scale models. Weakly labelled data is an alternative where a clip is annotated for presence or absence of instruments without specifying the times at which an instrument is sounding. This study investigates how TCN model compares to a Long Short-Term Memory (LSTM) model while trained on weakly labelled dataset. The results showed successful training of both models along with generalisation on a separate dataset. The comparison showed that TCN performed better than LSTM, but only marginally. Therefore, from the experiments carried out it could not be explicitly concluded if TCN is convincingly a better choice over LSTM in the context of instrument detection, but definitely a strong alternative. / Polyfonisk eller multipel musikinstrumentdetektering är ett svårt problem jämfört med att detektera enstaka eller soloinstrument i en ljudinspelning. Eftersom musik är tidsseriedata kan den modelleras med hjälp av sekvensinlärningsmetoder inom djup inlärning. Nyligen har ’Temporal Convolutional Network’ (TCN) visat sig överträffa konventionella ’Recurrent Neural Network’ (RNN) på flertalet sekvensmodelleringsuppgifter. Även om det har skett betydande förbättringar i metoder för djup inlärning, blir dataknapphet ett problem vid utbildning av storskaliga modeller. Svagt märkta data är ett alternativ där ett klipp kommenteras för närvaro av frånvaro av instrument utan att ange de tidpunkter då ett instrument låter. Denna studie undersöker hur TCN-modellen jämförs med en ’Long Short-Term Memory’ (LSTM) -modell medan den tränas i svagt märkta datasätt. Resultaten visade framgångsrik utbildning av båda modellerna tillsammans med generalisering i en separat datasats. Jämförelsen visade att TCN presterade bättre än LSTM, men endast marginellt. Därför kan man från de genomförda experimenten inte uttryckligen dra slutsatsen om TCN övertygande är ett bättre val jämfört med LSTM i samband med instrumentdetektering, men definitivt ett starkt alternativ.

Thèse numérisée par la Division de la gestion de documents et des archives de l'Université de Montréal.

This thesis presents the first sub-quadratic circle graph recognition algorithm, and develops improved algorithms for two important hierarchical decomposition schemes: modular decomposition and split decomposition. The modular decomposition algorithm results from unifying two different approaches previously employed to solve the problem: divide-and-conquer and factorizing permutations. It runs in linear-time, and is straightforward in its understanding, correctness, and implementation. It merely requires a collection of trees and simple traversals of these trees. The split-decomposition algorithm is similar in being straightforward in its understanding and correctness. An efficient implementation of the algorithm is described that uses the union-find data-structure. A novel charging argument is used to prove the running-time. The algorithm is the first to use the recent reformulation of split decomposition in terms of graph-labelled trees. This facilitates its extension to circle graph recognition. In particular, it allows us to efficiently apply a new lexicographic breadth-first search characterization of circle graphs developed in the thesis. Lexicographic breadth-first search is additionally responsible for the efficiency of the split decomposition algorithm, and contributes to the simplicity of the modular decomposition algorithm.

This thesis presents the first sub-quadratic circle graph recognition algorithm, and develops improved algorithms for two important hierarchical decomposition schemes: modular decomposition and split decomposition. The modular decomposition algorithm results from unifying two different approaches previously employed to solve the problem: divide-and-conquer and factorizing permutations. It runs in linear-time, and is straightforward in its understanding, correctness, and implementation. It merely requires a collection of trees and simple traversals of these trees. The split-decomposition algorithm is similar in being straightforward in its understanding and correctness. An efficient implementation of the algorithm is described that uses the union-find data-structure. A novel charging argument is used to prove the running-time. The algorithm is the first to use the recent reformulation of split decomposition in terms of graph-labelled trees. This facilitates its extension to circle graph recognition. In particular, it allows us to efficiently apply a new lexicographic breadth-first search characterization of circle graphs developed in the thesis. Lexicographic breadth-first search is additionally responsible for the efficiency of the split decomposition algorithm, and contributes to the simplicity of the modular decomposition algorithm.

Computational learning theory is a branch of theoretical computer science that re-imagines the role of an algorithm from an agent of computation to an agent of learning. The operations of computers become those of the human mind; an important step towards illuminating the limitations of artificial intelligence. The central difference between a learning algorithm and a traditional algorithm is that the learner has access to an oracle who, in constant time, can answer queries about that to be learned. Normally an algorithm would have to discover such information on its own accord. This subtle change in how we model problem solving results in changes in the computational complexity of some classic problems; allowing us to re-examine them in a new light. Specifically two known result are examined: one positive, one negative. It is know that one can efficiently learn Deterministic Finite Automatons with queries, not so of Non-Deterministic Finite Automatons. We generalize these Automatons into Labeled Transition Systems and attempt to learn them using a stronger query.

Thesis (MscAgric (Horticulture))--University of Stellenbosch, 2008. / ‘Brookfield Gala’ apple trees were planted out in July 2003 in a Dundee soil form, consisting of well-aerated sandy loam soil. During the first 12 months trees received young tree solutions high in nitrogen. The nutrient solution of the 2nd leaf trees was based on a yield estimation of 10 ton. ha-1 plus 30%. Nutrient solutions for the 3rd leaf trees were based on 25 ton. ha-1 yield estimations and adapted upwards. Seasonal uptake and distributions were determined for macro and micro elements, using twoand three-year-old apple trees during the seasons 2004/2005 and 2005/2006. In the bearing apple trees the macro nutrient accumulated rapidly from late winter to late autumn. Prior to leaf drop most of the N, P, S, Mg and a small portion of K were redistributed back into the permanent parts of the tree. On the other hand, all Ca in the leaves was lost through leaf drop. Apple fruit contains comparatively large quantities (±60.2%) of K, which are removed during harvest. Guidelines for minimum and maximum nutritional requirements based on the amount necessary to produce 1 kg fruit were determined. For the 3rd leaf trees the minimum macro nutrient requirements (g. kg-1 yield) of N, P, K, Ca, Mg and S were ±1.7, ±0.3, ±2.3, ±0.5, ±0.2 and ±0.2, respectively. The maximum nutrient requirements (g. kg-1 yield) for N, P, K, Ca, Mg and S were ±2.6, ±0.4, ±3.3, ±1.9, ±0.4 and ±0.2, respectively. For the 3rd leaf trees the minimum micro nutrient requirements (mg. kg-1 yield) of Na, Mn, Fe, Cu, Zn, B and Mo were ±75.1, ±1.3, ±28.7, ±0.9, ±3.0, ±5.7 and ±0.3, respectively. The maximum nutrient requirements (mg. kg-1 yield) of Na, Mn, Fe, Cu, Zn, B and Mo were ±102.9, ±7.8, ±32.6, ±1.1, ±6.5, ±7.6 and ±0.3, respectively. Labelled N uptake and distribution for two- and three-year-old apple trees were also determined during the same seasons. The labelled N uptake and distribution results indicated that there was a low labelled N uptake in the initial growth stages, suggesting the importance of internal N reserves for plant development at the beginning of the season. In the active growing period more than 60% of the labelled N was found in the new growth. Uptake efficiency improved as the trees grew older. The effect of different nutrient levels on tree growth, yield and fruit quality was assessed: lower (80%) than the standard (100%) and three higher (120%, 140% and 160%). Results indicated that different nutrient levels had no effect on yield, blush or TSS during the 18 months of application over two bearing seasons. The application of biological products (humic acid, and compost plus compost extract) over a period of 18 months had a significant influence on the TSS, malic acid and citric acid concentrations. A tendency towards an increase in total fine root number and length occured with the addition of biological ameliorant.