The objective of this research is to explore the use of ionic liquds in crystal engineering and drug delivery. Ionic liquids have a wide range of applications in pharmaceutical field due to their unique physicochemical propertie ssuch as chemical, thermal stability, low melting point, nonvolatility, nonflamability, low toxicity and recyclability which offer unique and interesting potential for pharmaceuitcal applications. Currently, many research groups are working on the development of ionic liquids to use in this field but there is need to develop systematic understanding about new techniques for synthesis and applications of ionic liquids to obtain new crystal form and potential of drug ionic salts. The synthesis of fifteen phosphonium ionic liquids under microwave irradiation and their physicochemical properties was investigated. The reaction time was significantly reduced compared to conventional methods, and higher yields were reported. The crystallisation of pharmaceutical drugs such as sulfathiazole, chlorpropamide, phenobarbital and nifedipine were investigated using imidazolium ionic liquids. The supramolecular complex of sulfathiazole and phenobarbital with imidazolium ionic liquids and polymorphic change in chlorpropamide was achieved. The ionic liquids provides unique environment for the crystallisation. The imidazolium salts of ibuprofen and diclofenac were synthesised and evaluated for physicochemical properties and their pharmaceutical performances especially transdermal absorption. The investigation of physicochemcal properties and pharmaceutical performance of imidazolium drug salts indicated opportunity to optimise lipophilicity and other physicochemical properties such as molecular size, osmolality, viscosity to achieve desired skin deposition and permeation. This study will provide a new approach to design of new drug salts develop using the interdisciplinary knowledge of chemical synthesis and drug delivery. / Social Justice Department, Government of Maharashtra, India.

Tesis por compendio / [ES] El melón (Cucumis melo L.) es actualmente uno de los cultivos con mayor importancia económica en el mundo. La amplia variabilidad genética intraespecífica que presenta permite el estudio para su explotación del control genético de un amplio abanico de caracteres tanto agronómicos como de calidad del fruto. En los últimos años se han desarrollado un gran número de marcadores moleculares y de herramientas genómicas en melón, que facilitan el desarrollo de nuevas poblaciones de mejora. Las líneas de introgresión (ILs) son un conjunto de líneas que contienen un fragmento cromosómico de un parental donante, normalmente exótico, en un fondo genético común normalmente de una variedad de élite. Estas colecciones son apropiadas para el estudio de caracteres cuantitativos y para la introducción de alelos exóticos favorables en cultivares comerciales. En la presente tesis doctoral se describe el desarrollo de una colección de ILs empleando la entrada japonesa 'Ginsen makuwa', como parental donante y el cultivar francés 'Vedrantais' como parental recurrente. Los sucesivos genotipados en generaciones tempranas mediante la plataforma Agena Bioscience y High Resolution Melting, han mejorado la eficiencia en el proceso de obtención de las ILs (cinco generaciones). Esta colección incluye 27 ILs, que posteriormente se han caracterizado mediante un genotipado de alta densidad (Genotyping by Sequencing). Éstas presentan un promedio de 2,7 introgresiones/IL con un 94% de recuperación del fondo genético 'Vedrantais', representando un 96,8% del genoma donante. El análisis de los datos de fenotipado en tres ambientes y el genotipado dió lugar a la detección de 86 QTLs (Quantitative Tratit Loci), de los que 74 fueron estables en al menos dos ambientes. De éstos, 3 QTLs están relacionados con aspectos de floración, 4 con la precocidad de maduración del fruto, 33 con aspectos morfológicos (forma del fruto, reticulado y espesor de la corteza), 12 con el proceso de maduración (presencia de aroma, capa de abscisión, firmeza de la pulpa), 16 con el color de la pulpa, 5 con el color interno de la corteza y 1 con el contenido en sólidos solubles. Algunos de los QTLs descritos en esta tesis han sido identificados en trabajos previos, lo que da solidez a las regiones detectadas, otros, en cambio, resultan novedosos y, por tanto, muy interesantes, pues constituyen un recurso muy valioso tanto para la búsqueda de genes candidatos como para el empleo de estos alelos en programas de mejora. De entre las ILs más prometedoras, destaca MAK_10-1 por presentar un bloqueo del climaterio, lo cual se traduce en una mayor vida postcosecha, característica muy buscada en el mercado internacional. Los efectos de la introgresión en el cromosoma 10 son la ausencia de aroma externo y la mayor firmeza de la pulpa, además del mayor contenido de sólidos solubles en pulpa. Además, se han localizado varios genes candidatos involucrados en la regulación transcripcional y de señalización de etileno durante la maduración del fruto. Por otro lado, se describen otras líneas potencialmente interesantes, así como genes candidatos, para proporcionar diversidad de tamaños, formas, color de la pulpa y perfil aromático al mercado de tipos cantalupo. Respecto al perfil de compuestos volátiles (VOCs) analizado en las ILs, se encontró que las introgresiones Makuwa en general disminuyeron el contenido en compuestos aromáticos. A pesar del efecto ambiental notable, se pudieron asociar ciertas regiones genómicas a ciertos perfiles de VOCs, identificando a su vez algunos genes candidatos involucrados en diferentes rutas de biosíntesis de aromas. La dificultad de recuperar ciertos perfiles aromáticos en los programas de mejora se pone de manifiesto por el elevado número de regiones y genes implicados, así como por efectos pleiotrópicos que afectan a la producción de aromas y que se describen en esta tesis como el bloqueo del climaterio o / [EN] Melon (Cucumis melo L.) is one of the most economically important crops in the world. The wide intraspecific genetic variability that it presents allows the study of a wide range agronomic and fruit quality traits. In recent years, a large number of molecular markers and genomic tools have been developed in melon, which is a resource that facilitates the development of new breeding populations. Introgression Lines (ILs) are a set of lines that contain a chromosomal fragment of a donor parent, usually wild or exotic, in a common genetic background usually an elite variety. These collections are appropriate for the study of quantitative traits and, above all, for the introduction of exotic alleles in modern cultivars. This doctoral thesis describes the development of a collection of ILs using the Japanese accesion 'Ginsen makuwa', as an exotic donor parent, and the French cultivar 'Vedrantais' as a recurrent parent. Successive genotyping in early generations through the Agena Bioscience platform and High Resolution Melting, have improved efficiency in the process of obtaining ILs (five generations). This collection includes 27 ILs, which have subsequently been characterized by high-density genotyping (Genotyping by Sequencing). These have an average of 2.7 introgressions / IL with a 94% 'Vedrantais' genetic background, representing 96.8% of the donor genome 'Ginsen makuwa'. The analysis of phenotyping data in three environments and genotyping resulted in the detection of 86 QTLs (Quantitative Tratit Loci), of which 74 were stable in at least two environments. Of these, 3 QTLs related with flowering aspects, 33 QTLs related with the mophological fruit (fruit shape, netting and rind thickness), 12 QTLs related with ripening behaviour (presence/absence of aroma, abscission layer and flesh firmness), 16 QTLs were related with flesh color, 5 QTLs related with color of the inner rind and 1 related with the soluble solid concentration. Some of the QTLs described in this thesis have been identified in previous works, giving greater confidence to the detected regions, others, however, are novel and, therefore, very interesting, becouse they constitute a very valuable resource for the search for candidate genes and for the use of these alleles in improvement programs. Of the entire ILs collection, MAK_10-1 presented a blockade of the climacteric, which can translate into a longer post-harvest life, trait that is very in the international market. The effects of introgression on chromosome 10 are the absence of external aroma and the greater flesh firmness, in addition the higher soluble solids content in flesh. In addition, several candidate genes involved in transcriptional regulation and ethylene signaling during fruit ripening have been located. On the other hand, other potentially interesting lines and candidate genes, are described to provide diversity of sizes, shapes, flesh color and aromatic profile to the cantaloupe type market. Regarding the profile of volatile compounds (VOCs) analyzed in ILs, it was found that Makuwa introgressions generally decreased the content of aromatic compounds. Despite the remarkable environmental effect, certain genomic regions could be associated with certain VOCs profiles, identifying some candidate genes involved in different aromatic biosynthetic pathways. The difficulty of recover certain aromatic profiles in breeding programs is evidenced by the high number of regions and genes involved, as well as by pleiotropic effects that affect the aroma production and which are described in this thesis as the blocking of the climacteric or the flesh color due to the presence of carotenes. / [CA] El meló (Cucumis melo L.) és actualment un dels cultius amb major importància económica en el món. La seua gran variabilitat genètica intraespecífica permet l'estudi per a la seua explotació del control genètic d'un gran ventall de caràcters tant agronòmics com de qualitat del fruit. En els últims anys s'han desenvolupat un gran nombre de marcadors moleculars i de ferramentes genòmiques en meló, que faciliten el desenvolupament de noves poblacions de millora. Les línies de introgressió (ILs) són un conjunt de línies que contenen un fragment cromosòmic d'un parental donant, normalment exòtic, en un fons genètic normalment d'una varietat d'èlit. Estes col·leccions són útils per a l'estudi de caràcters quantitatius, a més de per a la introducció d'al·lels exòtics favorables en cultivars comercials. En la present Tesi Doctoral es descriu el desenvolupament d'una col·lecció d'ILs amb l'entrada japonesa 'Ginsen makuwa' com parental donant i el cultivar francés 'Vedrantais' com parental recurrent. Els successius genotipatges en generacions primerenques, mitjançant la plataforma Agena Bioscience i High Resolution Melting, han millorat l'eficiència en el procés d'obtenció de les ILs (cinc generacions). Esta col·lecció inclueix 27 ILs que posteriorment s'han caracteritzat mitjançant genotipatge per seqüenciació. Estes presenten un promedi de 2,7 introgressions/IL amb un 94% de recuperació del fons genètic 'Vedrantais', representant un 96,8% del genoma donant. L'anàlisi de les dades de fenotipatge en tres ambients i el genotipatge, facilità la detecció de 86 QTLs (Quantitative Trait Loci), dels quals 74 foren estables en al menys dos ambients. D'estos, 3 QTLs estan relacionats amb aspectes de floració, 4 amb la precocitat de maduració del fruit, 33 amb aspectes morfològics (forma del fruit, reticulat, espessor pell), 12 amb el procés de maduració (presència d'aroma, capa d'abscisió, fermesa de la polpa), 16 amb el color de la polpa, 5 amb el color intern de la pell i 1 amb el contingut en sòlids solubles. Alguns dels QTLs descrits en la Tesi han sigut identificats en treballs previs, el que dóna solidesa a les regions detectades, altres en canvi, resulten nous i, per tant, molt interessants, ja que constitueixen un recurs valuós tant per a la recerca de gens candidats com per a l'ús d'estos al·lels en programes de millora. D'entre les ILs prometedores, destaca MAK_10-1 per presentar un bloqueig del climateri, el qual es tradueix en una major vida postcollita, característica molt buscada en el mercat internacional. Els efectes de la introgressió en el cromosoma 10 són l'absència d'aroma extern i la major fermesa de la polpa, a més del major contingut en sòlids solubles. S'han localitzat diversos gens candidats involucrats en la regulació transcripcional i de senyalització d'etilè durant la maduració del fruit. Per altra banda, es descriuen altres línies potencialment interessants, així com gens candidats, per a proporcionar diversitat de grandària, forma, color de la polpa i perfil aromàtic al mercat de tipus cantalupo. Respecte al perfil de compostos volàtils (VOCs) analitzat en les ILs, es trobà que les introgressions Makuwa en general van disminuir el contingut en compostos aromàtics. Malgrat el efecte ambiental notable, es pogueren associar certes regions genòmiques a certs perfils de VOCs, identificant alguns gens candidats en diferents rutes de biosíntesis d'aromes. La dificultat de recuperar certs perfils aromàtics en els programes de millora es posa de manifest per l'elevat nombre de regions i gens implicats, així com pels efectes pleiotròpics que afecten a la producció d'aromes i que es descriuen en esta Tesi, com el bloqueig del climateri o la coloració de la polpa per presència de carotens. / Perpiñá Martín, G. (2020). Desarrollo de líneas de introgresión en melón para la mejora de la calidad de esta especie [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/147113 / Compendio

[pt] A dissertação aborda um problema real de reprogramação de uma frota de embarcações do tipo PLSV (Pipe Laying Support Vessel), responsáveis pelas interligações de poços petrolíferos submarinos. O cronograma de curto prazo dessas embarcações está sujeito à inúmeras incertezas inerentes às operações realizadas, acarretando em ociosidade nas embarcações ou postergações na produção de petróleo, que podem resultar em prejuízo de milhões de reais. Uma metaheurística ILS (Iterated Local Search) é proposta para atender a frequente demanda por reprogramações dos PLSVs. O método é composto de uma fase inicial de viabilização, para tratar potenciais inconsistências nas programações. Na sequência, iterativamente, são realizadas perturbações na solução por meio de movimentos de swap e aplicada uma busca local baseada na vizinhança insert, a fim de fugir de ótimos locais e encontrar soluções que aprimorem o cronograma. Foram feitos experimentos com diferentes parâmetros e critérios do ILS, sendo definidas duas abordagens aplicadas a dez instâncias oriundas de uma programação real de PLSVs. A partir de uma função de avaliação, capaz de medir o impacto operacional na programação, o ILS proporcionou uma melhoria média nos cronogramas acima de 91 por cento, quando comparados aos cronogramas originais. As soluções foram obtidas em um tempo computacional médio de 30 minutos, aderente ao processo da companhia. Em função dos resultados alcançados, o método provou ser uma boa base para uma ferramenta de apoio à decisão para a reprogramação dos PLSVs. / [en] This dissertation addresses a real-life rescheduling problem of a Pipe Laying Support Vessels (PLSVs) fleet, in charge of subsea oil wells interconnections. The short-term schedule of these vessels is subject to uncertainties inherent to its operations, resulting in ships idleness or delays in oil production, which may lead to losses of millions of Brazilian Reais. A method based on the ILS (Iterated Local Search) metaheuristic is proposed to meet the frequent demand of PLSVs rescheduling. The first step of this method aims to find a feasible initial solution from an incoming schedule with potencial inconsistencies. The following steps consists in, iteratively, performing a perturbation on a solution through swap movements and applying a local search based on the insertion neighborhood, in order to escape from local optimal and find better solutions. Extensive preliminary experiments were conducted considering different ILS parameters setups. The two most performing setups were selected and applied to ten instances of a real PLSV schedule. Taking into account an objective function that measures the operational impact on schedules, the ILS provided an average improvement above 91 percent in schedules when compared to the original planning. These solutions were obtained in an average computational time of 30 minutes, which fits in the company process. The obtained results showed that the proposed method might be a basis for a decision support tool for the PLSVs rescheduling problem.

Le catalogue occupe une place privilégiée dans l’offre de service des bibliothèques universitaires, pivot de l’intermédiation. Depuis 10 ans, il traverse une crise grave, voyant les usagers le délaisser à la faveur des moteurs de recherche généralistes. Le web, plus qu’un sérieux concurrent, devance aujourd’hui les systèmes d’information documentaires, et devient le point d’entrée principal pour la recherche d’information. Les bibliothèques tentent de structurer un espace documentaire qui soit habité par les usagers, au sein duquel se développe l’offre de service, mais celle-ci se présente encore comme une série de silos inertes, sans grande possibilité de navigation, malgré de considérables efforts d’ingénierie et des pistes d’évolution vers les outils de découverte. La profession, consciente de cette crise profonde, après avoir accusé les remous occasionnés par la dimension disruptive du numérique, cherche des moyens pour adapter et diversifier son offre, fluidifier la diffusion de l’information, et se réinvente un rôle d’intermédiation en cherchant à tirer profit des nouvelles pratiques des usagers, de leurs nouvelles attentes, et de nouvelles perspectives. Les bibliothèques placent leur espoir dans de nouveaux modèles de données, tentent d’y ajouter un niveau d’abstraction favorisant les liaisons avec l’univers de la connaissance. L’évolution vers le web sémantique semble une opportunité à saisir pour valoriser les collections et les rendre exploitables dans un autre contexte, au prix d’importants efforts que cette analyse tente de mesurer. Une approche constructiviste fondée sur l’observation participante et le recueil de données offre une vision issue de l’intérieur de la communauté des bibliothèques sur l’évolution des catalogues et des outils d’intermédiation, et ouvre des perspectives sur leurs enjeux. / The catalog takes up a special position in the supply of services of academic libraries, as a pivot for the intermediary between users and information professionals who carry the responsibility for building up collections. For 10 years, through a serious crisis, they’ve been seeing their patrons preferring the general or commercial search engines. The Web is more than a serious competitor today, ahead of the document information systems, and became the main access point for information retrieval. Libraries are trying to structure an information space that is temporarily or permanently inhabited by users, in which the service offering is developed, but it is still presented as a series of silos, with few opportunities of navigation between them despite considerable engineering efforts and a perspective of evolution towards discovery tools. The profession, having become aware of this deep crisis after accusing eddies caused by the breakdown of the digital switch, looking for ways to adapt and diversify its offering, streamlines the dissemination of information, and reinvents its roles, trying to take advantage of new practices of users, new expectations and new prospects. Libraries put their hope in new data models, trying to add a level of abstraction promoting links with the world of knowledge. The evolution towards the Semantic Web seems to be a valuable opportunity to enhance the collections and make them usable in another context, at the expense of significant efforts sized up by this analysis. A constructivist approach based on participant observation and data collection offers a vision of the outcome within the library community on the development of catalogs and intermediation tools, and an outlook on their issues.

No description available.

隨著時代的變遷，圖書館員和使用者對於圖書館自動化系統的功能和現況漸漸產生許多不滿與問題。由於系統的開發過程封閉且原始碼無法取得，使圖書館只能另覓其他的自動化系統產品。開放程式的發展在二十一世紀隨著網際網路的發展受到重視。開放程式的圖書館自動化系統讓使用者除了使用還可以有複製、散佈、研究、改寫、再利用的自由。 本研究旨在探討台灣開放程式圖書館自動化系統的引進與發展現況，以Koha系統為研究對象，首先由文獻探討獲得圖書館自動化的現況、開放程式碼的發展，及開放程式應用於圖書館自動化系統之現況，並依據TAM科技接受模式為基礎設計問卷問項與進行分析，接著由訪談的方式深入瞭解台灣使用Koha系統的現況與問題，訪談對象包括使用Koha系統之圖書館以及與Koha系統相關的單位或個人，最後進行問卷調查與訪談資料整理分析。 本研究結果如下：1.台灣開放程式圖書館自動化系統的現況：台灣引進Koha系統始於2005年，由輔大圖資系毛慶禎副教授提倡Koha中文繁體的發展。使用對象多為中小學圖書館與對開放程式有興趣者，由於政府政策的影響，未來繼續使用Koha系統之中小學圖書館將銳減。2.圖書館使用開放程式圖書館自動化系統之動機：(1)圖書館未自動化；(2)缺乏購買系統的經費；(3)經由推廣取得；(4)對應用開放軟體有興趣；(5)過去使用過的圖書館自動化系統不成功；(6)教學使用；(7)有良好的技術支援協助。3.對Koha系統接受度不高：Koha系統由於技術支援、易用性與滿意度不足，以及受到政府政策影響，導致其接受度不高。4.成功使用開放程式圖書館自動化系統之因素：(1)教育訓練與交接完整；(2)其他人力支援；(3)技術支援；(4)介面親和；(5)功能容易使用；(6)館員態度積極。5.使用開放程式圖書館自動化系統失敗之原因與困難：(1)教育訓練不足；(2)缺乏人力；(3)缺乏技術支援；(4)功能不全；(5)系統說明手冊不完整；(6)介面不親和；(7)技術門檻較高。 本研究結果可提供台灣未來發展開放程式圖書館自動化系統的參考方案，觀察使用Koha系統圖書館失敗的原因以及與Koha系統相關單位兩方的觀點與困難，發現其中產生的問題，給予Koha系統、使用者與在地團隊建議。 / As the wheel of time turns, librarians and users of the integrated library system(ILS) become to be unsatisfied the features of ILS. Because of the developing process is closed and the unavailability of the source code, libraries have to try other ILS products for further development. Open source ILS is one of options, it gives users the freedom to copy, distribute, research, rewrite and reuse. The purpose of this research is to study the current developing situation of open source ILS in Taiwan. We use Koha system as research case. By studying related papers, we captured the current situation of ILS, the development of open source, and the application of open source ILS. Using the questionnaires based on technology acceptance model (TAM) and interviews, we enhance our understanding of the current use and question about the Koha system in Taiwan. The findings are as follows: 1.Current view of open source ILS in Taiwan: Prof. Mao has been distributing the developing of Koha in traditional Chinese since 2005. Users who used Koha system are mainly libraries in junior-high schools and elementary schools and those who are interested in Koha system. Due to the policy of Ministry of Education, the usage of Koha system in libraries in senior-high schools and elementary schools will be significantly less after 2010. 2. Reasons why libraries use open source ILS were categorized as follows :(1)Libraries was not automated; (2)Libraries were not automated successfully; (3)Libraries adopted Koha from promotion; (4)Libraries had insufficient budget; (5)Libraries had good technical supports; (6)Schools used Koha for education training purpose; (7)Schools were interested in the usage of open source. 3.The reasons of low acceptance of the Koha system: (1)Lack of technical supports; (2)Koha system was hard to use for average users; (3)Ministry of Education command the elementary and secondary schools to adopt new ILS. 4.Factors of the success adoption of the open source ILS: (1)Complete education training for users; (2)Other human resource support; (3)Technical support; (4)Friendly user interface; (5)Ease of use; (6)Positive attitude. 5.Reasons of the failure of library automation system and its difficulties: (1)Lack of training; (2)Lack of human support; (3)Lack of technical supports; (4)Incomplete features; (5)Incomplete system manual; (6)Unfriendly user interface; (7)Higher technology requirement.

RESUME: Le travail de recherche rapporté dans cette thèse concerne lamélioration de traceurs marqués au fluor-18 utilisés en routine clinique : la 2-[18F]fluoro-L-tyrosine et le 2-désoxy-2-[18F]fluoro-D-glucose. Les résultats relatifs à lacide aminé, de valeur confirmative pour les connaissances publiées antérieurement dans la littérature, consistent en une validation chez le rat qui entérine le potentiel de ce traceur pour létude de la vitesse de synthèse des protéines cérébrales in vivo. Les perspectives futures pour ce traceur sont dès lors lextension de son utilité dans le domaine de loncologie et son utilisation pour létude de phénomènes physiologiques neurologiques. Durant ce travail, des techniques décrites dans la littérature, mais non pratiquées au CRC ont fait lobjet dune implémentation et sont maintenant accessibles (modèle du rat vigile, méthodes de synthèse de polymères à empreinte moléculaire). La partie principale du travail concerne la récupération du [18F]fluorure et son utilisation pour le marquage nucléophile sans étape dévaporation. La synthèse du 2-désoxy-2-[18F]fluoro-D-glucose a servi de réaction témoin pour tester lapplicabilité des méthodes développées dans ce cadre. Deux stratégies différentes, lune utilisant des supports ioniques et des solvants protiques, lautre utilisant des supports non ioniques et des solvants non protiques, ont permis datteindre les buts fixés avec des rendements dincorporation du [18F]fluorure de même ordre de grandeur que ceux obtenus en radiochimie usuelle du fluor-18. La méthode utilisant les supports non ioniques a par ailleurs démontré sa grande généralité vis-à-vis de précurseurs divers, aliphatiques et aromatiques, dans des conditions de marquage diverses, notamment à température modérée. Les perspectives de ces méthodes nouvelles pour la fabrication des traceurs TEP tirent parti de la possibilité de les implanter dans un automate miniaturisé (milli- ou micro-réacteur), à visée synthétique ou analytique. Lefficacité et la simplicité des méthodes de récupération sans évaporation mises au point dans ce travail les destinent à être utilisées aussi bien en développement des traceurs quen synthèse de routine. Elles sont applicables aussi bien à léchelle des automates courants quà celle des futures applications microfluidiques. Par ailleurs, nous sommes persuadés de lintérêt des polymères à empreinte moléculaire dans le créneau des méthodes analytiques. Egalement applicables à des systèmes miniaturisés, ils devraient aider à la réalisation danalyses automatisées des produits finis et à une libération accélérée. Le gain de temps et les moindres pertes de principe actif conduiront alors à une meilleure disponibilité des traceurs TEP et à leur participation accrue aux objectifs de la médecine personnalisée. Nous pensons dès lors avoir ouvert quelques pistes de recherche prometteuses pour la mise en application de ses nouvelles technologies au domaine de la tomographie à émission de positon. / SUMMARY: The results reported in this work concern the improvement of 18-fluorine labelled radiopharmaceuticals used in routine clinical applications: 2-[18F]fluoro-L-tyrosine and 2-deoxy-2-[18F]fluoro-D-glucose. The study of the metabolism of non carrier added 2-[18F]fluoro-L-tyrosine in rats confirms that this tracer is rapidly and extensively incorporated into cerebral proteins and is therefore well suited to the assessment of Protein Synthesis Rate (PSR) in vivo by PET. A correction for the appearance of metabolites is advised for quantitative interpretation of the data. An improvement in the radiosynthesis is necessary to make 2-[18F]fluoro-L-tyrosine widely available for its application in oncology and to envisage the extended use of this tracer for the study of the protein synthesis in other physiological or pathological processes. The second chapter deals with use of molecular imprints in the PET radiochemistry. The molecularly imprinted polymers were synthetized, characterized and tested for the production of specific PET tracers and the plasma analysis of the parent metabolites. The third part of the work consisted in a development of new methods for the [18F]fluoride recovery in order to permit the labelling of different precursors through nucleophilic substitution without the evaporation step classically performed in 18-fluorine radiochemistry. The synthesis of 2-deoxy-2-[18F]fluoro-D-glucose has been used as a tool for the evaluation of the developed methods. Two strategies were considered to concentrate and recover the [18F]fluoride. The first one used ionic solid supports and protic solvents. The second one relied on the use of non ionic solid supports and non protic solvents. Both strategies led us to reach [18F]fluoride incorporation yields as high as in classical radiosyntheses with evaporation. Ionic liquids and tertiary alcohols were also evaluated in order to improve the tolerance of the [18F]fluoride nucleophilic substitution to water. The molecularly imprinted polymers and the new methods for the recovery of [18F]fluoride will now be tested for the implementation of PET tracers radiosynthesis and quality control into microchip devices.

Competitive and high-risk environments require complex high technology systems, which need to be supported and maintained over their respective life cycles. These systems often have a significant consequence of failure, and require complex management systems to achieve their operational objectives. Significant leadership and management challenges exist, not only in South Africa, but also in other developing countries, where systems may be utilised beyond the lifespan they were designed for and are susceptible to obsolescence. This study was conducted by following a structured process; the research consisted of three stages. The first stage dealt with the research problem, including the delimitations of the study. The second stage was further divided into three phases. The first phase deconstructed the appropriate literature, which included the interpretation of numerous definitions of logistics, integrated logistics support, and the integrated logistics support elements. In addition, the research was grounded in the fields of operations management, supply chain management and integrated logistics support. The second phase focused on the deconstruction of six case studies from four different high technology complex systems. From the analysis of the first two phases followed the third phase of research, which focused on the identification of areas requiring further research. Further research was conducted by means of a questionnaire, the results of which were analysed for variable dependency and variable association. The third stage of the research included the collation and analysis of the findings of the first two stages of research. The analysis utilised the principles of Mode 2 research and design science research, whereby an ILS framework and associated grounded technological rules have been recommended. These recommendations are robust in nature, as they can be applied in the most challenging environment and circumstances as identified. Furthermore, by grounding the theory in the disciplines of operations management, supply chain management and integrated logistics support, the reliability, validity, relevance, and applicability of the study could be substantiated. This implied that the generated theoretical knowledge could be transferred to and applied in practice, and as such, an organisation can reap substantial value added benefits, and gain considerable competitive advantage in the market place by applying this developed ILS framework and associated ILS grounded technological rules. / Business Leadership / D. BL.

Competitive and high-risk environments require complex high technology systems, which need to be supported and maintained over their respective life cycles. These systems often have a significant consequence of failure, and require complex management systems to achieve their operational objectives. Significant leadership and management challenges exist, not only in South Africa, but also in other developing countries, where systems may be utilised beyond the lifespan they were designed for and are susceptible to obsolescence. This study was conducted by following a structured process; the research consisted of three stages. The first stage dealt with the research problem, including the delimitations of the study. The second stage was further divided into three phases. The first phase deconstructed the appropriate literature, which included the interpretation of numerous definitions of logistics, integrated logistics support, and the integrated logistics support elements. In addition, the research was grounded in the fields of operations management, supply chain management and integrated logistics support. The second phase focused on the deconstruction of six case studies from four different high technology complex systems. From the analysis of the first two phases followed the third phase of research, which focused on the identification of areas requiring further research. Further research was conducted by means of a questionnaire, the results of which were analysed for variable dependency and variable association. The third stage of the research included the collation and analysis of the findings of the first two stages of research. The analysis utilised the principles of Mode 2 research and design science research, whereby an ILS framework and associated grounded technological rules have been recommended. These recommendations are robust in nature, as they can be applied in the most challenging environment and circumstances as identified. Furthermore, by grounding the theory in the disciplines of operations management, supply chain management and integrated logistics support, the reliability, validity, relevance, and applicability of the study could be substantiated. This implied that the generated theoretical knowledge could be transferred to and applied in practice, and as such, an organisation can reap substantial value added benefits, and gain considerable competitive advantage in the market place by applying this developed ILS framework and associated ILS grounded technological rules. / Business Leadership / D. BL.