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Made available in DSpace on 2016-12-08T16:35:09Z (GMT). No. of bitstreams: 1 fernando.pdf: 1281642 bytes, checksum: 63e0757e55840e2ccfbd150ef97c1c4c (MD5) Previous issue date: 2009-02-26 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The growing addition of information and communication technologies in history teaching is what triggers the reflections in this essay. Used as a reference of analysis the thirty programs by Series Brasil 500 Anos, which is an audio-visual educational device especially designed to celebrate the nation 500th year widely distributed to public schools as part of the Kits Tecnológicos TV Escola. Organizing the dissertation in two large essays, first, used the Series Brasil 500 Anos to talk about wishes of past that mobilizing the configuration of a memory culture in the contemporaneous world. Posteriorly, understating itself as an audio-visual narrative which show curricular contents with allusions to national history considered worth to be taught and learned, discuss some mechanisms of embedding and disembedding of history teaching and curriculum in the contemporaneousness its. In this epistemological approach, the borders of the historiographical field are overflowed and a dialogue is developed with supposed theoretical- ethodologies originated from the different disciplines. So, as developed some impertinencies about nation education politics and programs with allusions to distribution of information and communication technologies in school quotidian, as suspected of the supposed metaphysic, redeemer and messianic nature of the contemporaneous scholar culture its / O crescente processo de inclusão de tecnologias da informação e comunicação no ensino de História é o que mobiliza as reflexões desta dissertação. Como vetor de análise, utilizo os trinta episódios que compõem a Série Brasil 500 Anos, um artefato educativo audiovisual especialmente produzido para as comemorações do quinto centenário da nação amplamente distribuido para as escolas públicas como parte dos Kits Tecnológicos TV Escola. Estruturando a dissertação em dois grandes ensaios, inicialmente, aproveito-me da Série Brasil 500 Anos para refletir sobre desejos de passado que impelem a configuração de uma cultura de memória no mundo contemporâneo. Posteriormente, entendendo-a como uma narrativa audiovisual que exibe entendimentos curriculares alusivos a histórias nacionais consideradas dignas serem ensinadas e aprendidas, discuto alguns dos mecanismos de desencaixe e reencaixe do ensino de História, assim como de seu currículo, na contemporaneidade. Nesse fazer epistemológico, transbordo as fronteiras do campo historiográfico e dialogo com pressupostos teoricometodológicos advindos de diferentes disciplinas. A partir desses arranjos, construo algumas impertinências sobre políticas e programas nacionais de educação voltados à difusão de tecnologias da informação e comunicação no cotidiano escolar, assim como desconfio de seu suposto caráter metafísico, redentor e messiânico da cultura escolar contemporânea

A incidência do melanoma cutâneo em pacientes adultos jovens tem aumentado consideravelmente nos últimos anos. Há, contudo, carência de conhecimentos clinicopatológicos e moleculares sobre os melanomas que ocorrem nessa faixa etária. O presente estudo teve por objetivo avaliar 132 casos de melanoma cutâneo primário em pacientes com idade entre 18 e 30 anos, com ênfase no estudo das características clínicas, histopatológicas e avaliação molecular das mutações nos genes BRAF, NRAS e KIT. Em relação aos achados clínicos e histopatológicos, houve predomínio de indivíduos do sexo feminino (61,4%), sendo o tronco o sítio anatômico mais comumente envolvido (44,3%) e o melanoma extensivo superficial o tipo histológico predominante (79,5%). A mutação V600E no gene BRAF (BRAFV600E) foi analisada em 93 casos, utilizando-se a técnica de RT-PCR. Essa mutação foi identificada em 38,7% (36/93) e, estatisticamente, associada à fase vertical de crescimento (p = 0,01), infiltrado inflamatório discreto (p = 0,02) e presença de mitose intradérmica (p = 0,004). Houve, ainda, forte indício de associação com a presença de ulceração (p = 0,05). Todas essas variáveis apresentaram associação com pior prognóstico do melanoma cutâneo. Observou-se predomínio da mutação BRAFV600E em regiões anatômicas relacionadas à exposição solar intermitente. Nenhum caso de melanoma com fenômeno de regressão apresentou mutação BRAFV600E (p < 0,05). Não houve associação significativa entre BRAFV600E e sexo, tipo histológico, nível de Clark, índice de Breslow, elastose solar, invasão angiolinfática e perineural, satelitose, nevo melanocítico coexistente e sobrevida. A pesquisa de mutações NRAS, pela técnica de RT-PCR, detectou frequência de 3,95% (3/76). As três mutações encontradas foram do tipo 61K e ocorreram em pacientes do sexo masculino e em região de cabeça e pescoço. As mutações BRAFV600E e NRAS, quando presentes, eram mutuamente exclusivas. A frequência de mutações KIT, analisadas por sequenciamento, foi de 11,1% (3/27). As três mutações identificadas estavam localizadas no éxon 9 (G510, G498S e 489I). Houve concomitância de casos com mutação KIT tanto com NRAS, como com BRAFV600E. Devido ao pequeno número de casos com mutação em KIT e NRAS, não foi possível estabelecer correlações clínicas e histopatológicas com esses genes. Este estudo é o primeiro a descrever as mutações G510D e G498S no gene KIT em melanomas cutâneos. No presente estudo, a mutação BRAFV600E, em melanomas cutâneos de adultos jovens, correlacionou-se com características anatomoclínicas de pior prognóstico em relação aos melanomas selvagens para BRAFV600E / The incidence of cutaneous melanoma in young adults has dramatically increased in recent years. However, there is scarce data about the clinicopathological and molecular characteristics on the melanomas occurring at this age group. The present study aimed to evaluate 132 patients aged between 18 and 30 years with primary cutaneous melanoma with emphasis on the study of clinical, histopathological characteristics and molecular evaluation of mutations in BRAF, NRAS and KIT genes. Regarding the clinical and histopathological findings, the following results were found: female predominance (61.4%), trunk was the most commonly anatomical site involved (44.3%) and superficial spreading melanoma, was the most common histological type (79.5 %). The V600E mutation in BRAF (BRAFV600E) gene was analyzed in 93 cases, using RT-PCR. It was present in 38.7% (36/93) and statistically related to the vertical growth phase (p = 0.01), mild inflammatory infiltration (p = 0.02) and the presence of intradermal mitosis (p = 0.004). There was, also, strongly evidence of an association with the presence of ulceration (p = 0.05). Worse prognosis was associated with these variables. There was a predominance of BRAFV600E mutation in anatomical regions related to intermittent sun exposure. No cases of melanoma with BRAFV600E mutation showed regression phenomenon (p < 0.05). There was no significant association between BRAFV600E and gender, histological type, Clark level, Breslow thickness, solar elastosis, angiolymphatic and perineural invasion, sattelitosis, coexisting melanocytic nevus and survival. The presence of a mutation in NRAS, by RT-PCR was seen in 3.95% (3/76) of the cases. All these three mutations were of type 61K, occurred in male patients and the head and neck region. BRAFV600E and NRAS mutations, when present, were mutually exclusive. The frequency of KIT mutations, analyzed by sequencing, was 11.1% (3/27). The three mutations identified in this gene were located in exon 9 (G510, G498S and 489I). Concomitant mutations were found between KIT and NRAS and BRAFV600E. Due to the small number of KIT and NRAS mutated cases, it was not possible to establish clinical and histopathological correlations and mutation status in these genes. This study was the first to describe the G510D and G498S mutations in KIT gene in cutaneous melanomas. In the present study, BRAFV600E mutation in cutaneous melanoma of young adults correlated with anatomic and clinical features of worse prognosis compared to wild type

Pour devenir une importante destination touristique internationale et pas seulement subsaharienne, le Kenya a besoin de lieux et de produits touristiques renouvelés offerts de manière croissante par les sites mémoriels et les musées régionaux situés dans l’ensemble du pays, mis en tourisme récemment en direction des touristes domestiques. Cette nouvelle tendance permettra de décongestionner les sites et les régions touristiques phares (parcs de Masaï Mara, de Amboseli, lac Nakuru et la côte swahili), saturés dans leur fréquentation double, à la fois celle des touristes internationaux, mais aussi celle croissante, des touristes intérieurs. Grâce à l’approche multidisciplinaire (géographie du tourisme, celle du développement et celle de la culture), appuyée par les données obtenues à travers les entretiens semi-directifs, les questionnaires, les tables rondes, l’analyse documentaire et l’observation sur le terrain, notre recherche tente de démontrer comment le patrimoine matériel et immatériel des groupes ethno-culturel du Kenya occidental peut être mis en tourisme. Notre investigation traite de la région du lac Victoria et de Bungoma, principalement sur les sites d’Abasuba Rock Art Paintings, de Kit Mikayi et de Namakanda. Les populations locales autour de ces sites développent des stratégies différenciées en fonction de leur appartenance ethnique, que nous appréhendons du point de vue de la stratégie d’acteurs et des projets de développement touristiques. / To become an important international tourism destination and not only in Subsaharan, Kenya needs renewed tourism places and products majorly consisting of memorial sites and regional museums spread throughout the country, recently developed for domestic tourists. This new initiative will decongest the major tourist sites and regions (reserve of Masai Mara, parks of Amboseli, lake Nakuru and Swahili coast), saturated due to double visitation (international and domestic tourists) Through a multidisciplinary approach (geography of tourism, cultural geography and geography of development), supported by data collected through semi-direct interviews, focus groups, questionnaires, field observation and analysis of existing literature, our research attempts show how the material and immaterial cultural heritage of the ethno-cultural groups of Western Kenya can be developed for tourism. Our investigation examines the regions of lake Victoria and Bungoma, particularly the sites of Abasuba Rock Art Paintings, Kit Mikayi and Namakanda. The host communities of these sites are developing strategies informed by their ethnic affiliation, that we study from the point of view of stakeholders’ strategy and development of tourism projects.

Abstract Each year in Finland, approximately 5.7% of infants are born preterm, i.e., before 37 completed weeks of gestation. Preterm birth is a major cause of mortality and several neonatal morbidities, especially the respiratory diseases. Infants born very preterm (&#60;32 wk) are at higher risk of developing a chronic lung disease called bronchopulmonary dysplasia (BPD). The genetic factors predisposing to spontaneous preterm birth (SPTB) and BPD are incompletely known. The aims of this thesis project were to identify genetic factors that affect susceptibility to SPTB and BPD. Genetic case-control association studies were performed in mothers and infants of northern Finnish origin (SPTB study), or in multiple populations of very preterm infants of Finnish or European origin (BPD study). The candidate genes were selected based on their proposed roles in inflammation which is involved in both SPTB and BPD susceptibility. Additionally, the aim was to study the possible functional role of polymorphisms in the gene encoding surfactant protein B (SP-B) that have been shown previously to associate with pulmonary function. An association between Met31Thr polymorphisms in the gene encoding SP-D (SFTPD) and SPTB infants was found. The other collectin genes that were studied, encoding SP-A and mannose-binding lectin, did not associate with SPTB in mothers or infants. An intronic polymorphism in the gene encoding Kit ligand (KITLG) was associated with the risk of BPD in the northern Finnish and in the combined population that originated from Finland, Canada and Hungary. The role of KITLG in BPD was further supported by biomarker data, which showed higher concentrations of Kit ligand at the time of birth in infants that later developed BPD. The genes encoding interleukin 6 (IL-6), its receptors, IL-10, tumor necrosis factor alpha or glucocorticoid receptor did not associate with BPD susceptibility. Finally, a genetic variant 131Thr in the gene encoding SP-B (SFTPB) was associated with lower SP-B levels in vivo and delayed secretion in vitro. To date, there is no effective method to prevent SPTB, and especially the extremely preterm infants are at an increased risk of developing serious respiratory diseases. Better understanding of the mechanisms underlying both SPTB and BPD could help in the successful prediction of risk groups as well as in the design of new preventive and treatment strategies. / Tiivistelmä Noin 5,7 % lapsista syntyy Suomessa ennenaikaisesti, eli ennen kuin raskaus on kestänyt täydet 37 viikkoa. Ennenaikainen syntymä altistaa vastasyntyneen lapsen vakaville pitkäaikaissairauksille. Erityisesti hyvin pienillä keskosilla, jotka ovat syntyneet ennen 32. raskausviikkoa, on suurempi riski sairastua vakavaan hengitysvaikeuteen eli bronkopulmonaaliseen dysplasiaan, joka tunnetaan myös nimellä BPD-tauti. Perinnölliset tekijät vaikuttavat niin spontaanin ennenaikaisen syntymän (SEAS) kuin BPD-taudinkin taustalla, mutta nämä tekijät tunnetaan huonosti. Tässä väitöskirjatyössä pyrittiin tunnistamaan perinnöllisiä tekijöitä, jotka vaikuttavat SEAS:in ja BPD-taudin taustalla. Perinnöllisen taustan selvittämisessä ehdokasgeenien sisältämien muuntelevien kohtien esiintyvyyttä verrattiin terveiden verrokkien ja tautitapausten välillä. SEAS-tutkimuksessa tutkimusväestö koostui suomalaisista äideistä ja heidän lapsistaan. BPD-tutkimuksessa oli mukana hyvin ennenaikaisesti syntyneitä lapsia Suomesta, Kanadasta ja Unkarista. Tämän lisäksi kokeellisten tutkimusten avulla tutkittiin aiemmin keuhkosairauksiin liittyneen geenin muuntelevien kohtien osuutta sen koodaaman surfaktanttiproteiini (SP) B:n toiminnassa. Tutkimuksissa havaittiin SP-D:tä koodaavan geenin Met31Thr-polymorfismin olevan mahdollinen riskitekijä SEAS:lle lapsilla, mutta se ei selittänyt SEAS-riskiä äideissä. SP-A:ta ja mannoosia sitovaa lektiiniä koodaavilla geeneillä ei ollut yhteyttä SEAS-riskiin. Kit-ligandia koodaavan geenin intronissa sijaitseva polymorfismi selitti BPD-tautiriskiä pohjoissuomalaisessa sekä yhdistetyssä tutkimusväestössä. Lisäksi lapsilla, jotka myöhemmin sairastuivat BPD-tautiin, havaittiin suurempia Kit-ligandipitoisuuksia syntymähetkellä. Interleukiini 6:ta (IL-6), sen reseptoreita, IL-10:ta, tuumorinekroosifaktori-alfaa tai glukokortikoidireseptoria koodaavien geenien polymorfismien ja BPD-taudin välillä ei ollut yhteyttä. SP-B:tä koodaavan geenin Ile131Thr-polymorfismin Thr-variaatio liittyi alhaisempaan SP-B:n pitoisuuteen lapsivedessä sekä hidastuneeseen proteiinin tuottoon kokeellisessa solumallissa. Tulokset antavat uutta tietoa SEAS:n ja BPD-taudin perinnöllisestä taustasta. Tämä tieto voi auttaa synnytyksen käynnistymiseen sekä BPD-alttiuteen johtavien biologisten mekanismien selvittämisessä ja uusien hoitokeinojen kehittämisessä.

This Master’s thesis deals with working on development kit, which is used for RC ship model. The basis are programmable Nucleo STM32 microcontrollers, to which other used modules are connected. The goal is to test each component and create system for navigation of the ship and wireless communication between controller and ship. GPS module and compass are used to navigate and determine the direction of the ship. Controller and ship can communicate through bidirectional wireless modules with antenna. The RC ship model can be switched between manual and autonomous modes. The main result of this thesis is autonomous movement of the ship on to a predetermined GPS coordinates and parallel communication with the user.

El trabajo de investigación se basa principalmente en el desarrollo de la marca Hilli alli, la cual consiste en la producción y comercialización vía online y en tiendas especializadas de kits de frutas y verduras congeladas con toppings personalizados. Esto en respuesta a la problemática de no encontrar un kit saludable y práctico de preparar que brinde los nutrientes necesarios para las actividades diarias a nuestro público objetivo, el cual está compuesto por hombres y mujeres entre 18 y 35 años de Lima Metropolitana de los niveles socioeconómicos A y B que consuman productos nutritivos y orgánicos. Los experimentos realizados nos permitieron validar la intención de los consumidores finales mediante sus comentarios en las publicaciones de redes sociales y mensajes directos. Asimismo, se validó el interés por parte de las tiendas especializadas de contar con nuestro producto como parte de su catálogo de bienes ofrecido al público objetivo que apuntamos. La estructura del trabajo se divide inicialmente en la descripción de la problemática a solucionar y el respectivo diseño del modelo del negocio. Todas las fases del trabajo llegan a un punto en común: justificar la viabilidad del negocio. Por último, se quiere demostrar si la inversión del proyecto puede ser recuperada en el tiempo trazado. La inversión inicial que se requiere para este proyecto es de un monto total de 59,000.00 soles, Esto nos permitirá iniciar nuestras operaciones y solventar los gastos que se requieren. Finalmente, nuestro VAN resultante es positivo, lo cual lo hace rentable nuestro negocio. / The research work is mainly based on the development of the Hilli alli brand, which consists of the production and marketing via online and in specialized stores of kits of frozen fruits and vegetables with personalized toppings. This in response to the problem of not finding a healthy and practical kit to prepare that provides the necessary nutrients for their daily activities to our target audience, which is made up of men and women between 18 and 35 years old from Metropolitan Lima of the levels socioeconomic A and B who consume nutritious and organic products. The experiments carried out allowed us to validate the intention of the final consumers through their comments in the social network publications and direct messages, likewise, the interest on the part of specialized stores to have our product as part of their catalog of offered goods was validated. the target audience we are targeting. The structure of the work is initially divided into the description of the problem to be solved and the respective design of the business model. All phases of the work reach a common point: justify the viability of the business. Finally, we want to show whether the investment in the project can be recovered in the time set. The initial investment required for this project is a total amount of 59,000.00 soles. This will allow us to start our operations and pay for the required expenses. Ultimately, our resulting NPV is positive, which makes our business profitable. / Trabajo de investigación

Key-Value Stores (KVSs) are a type of non-relational databases whose data is represented as a key-value pair and are often used to represent cache and session data storage. Among them, Memcached is one of the most popular ones, as it is widely used in various Internet services such as social networks and streaming platforms. Given the continuous and increasingly rapid growth of networked devices that use these services, the commodity hardware on which the databases are based must process packets faster to meet the needs of the market. However, in recent years, the performance improvements characterising the new hardware has become thinner and thinner. From here, as the purchase of new products is no longer synonymous with significant performance improvements, companies need to exploit the full potential of the hardware already in their possession, consequently postponing the purchase of more recent hardware. One of the latest ideas for increasing the performance of commodity hardware is the use of slice-aware memory management. This technique exploits the Last Level of Cache (LLC) by making sure that the individual cores take data from memory locations that are mapped to their respective cache portions (i.e., LLC slices). This thesis focuses on the realisation of a KVS prototype—based on Intel Haswell micro-architecture—built on top of the Data Plane Development Kit (DPDK), and to which the principles of slice-aware memory management are applied. To test its performance, given the non-existence of a DPDKbased traffic generator that supports the Memcached protocol, an additional prototype of a traffic generator that supports these features has also been developed. The performances were measured using two distinct machines: one for the traffic generator and one for the KVS. First, the “regular” KVS prototype was tested, then, to see the actual benefits, the slice-aware one. Both KVS prototypeswere subjected to two types of traffic: (i) uniformtraffic where the keys are always different from each other, and (ii) skewed traffic, where keys are repeated and some keys are more likely to be repeated than others. The experiments show that, in real-world scenario (i.e., characterised by skewed key distributions), the employment of a slice-aware memory management technique in a KVS can slightly improve the end-to-end latency (i.e.,~2%). Additionally, such technique highly impacts the look-up time required by the CPU to find the key and the corresponding value in the database, decreasing the mean time by ~22.5%, and improving the 99th percentile by ~62.7%. / Key-Value Stores (KVSs) är en typ av icke-relationsdatabaser vars data representeras som ett nyckel-värdepar och används ofta för att representera lagring av cache och session. Bland dem är Memcached en av de mest populära, eftersom den används ofta i olika internettjänster som sociala nätverk och strömmande plattformar. Med tanke på den kontinuerliga och allt snabbare tillväxten av nätverksenheter som använder dessa tjänster måste den råvaruhårdvara som databaserna bygger på bearbeta paket snabbare för att möta marknadens behov. Under de senaste åren har dock prestandaförbättringarna som kännetecknar den nya hårdvaran blivit tunnare och tunnare. Härifrån, eftersom inköp av nya produkter inte längre är synonymt med betydande prestandaförbättringar, måste företagen utnyttja den fulla potentialen för hårdvaran som redan finns i deras besittning, vilket skjuter upp köpet av nyare hårdvara. En av de senaste idéerna för att öka prestanda för råvaruhårdvara är användningen av skivmedveten minneshantering. Denna teknik utnyttjar den Sista Nivån av Cache (SNC) genom att se till att de enskilda kärnorna tar data från minnesplatser som är mappade till deras respektive cachepartier (dvs. SNCskivor). Denna avhandling fokuserar på förverkligandet av en KVS-prototyp— baserad på Intel Haswell mikroarkitektur—byggd ovanpå Data Plane Development Kit (DPDK), och på vilken principerna för skivmedveten minneshantering tillämpas. För att testa dess prestanda, med tanke på att det inte finns en DPDK-baserad trafikgenerator som stöder Memcachedprotokollet, har en ytterligare prototyp av en trafikgenerator som stöder dessa funktioner också utvecklats. Föreställningarna mättes med två olika maskiner: en för trafikgeneratorn och en för KVS. Först testades den “vanliga” KVSprototypen, för att se de faktiska fördelarna, den skivmedvetna. Båda KVSprototyperna utsattes för två typer av trafik: (i) enhetlig trafik där nycklarna alltid skiljer sig från varandra och (ii) sned trafik, där nycklar upprepas och vissa nycklar är mer benägna att upprepas än andra. Experimenten visar att i verkliga scenarier (dvs. kännetecknas av snedställda nyckelfördelningar) kan användningen av en skivmedveten minneshanteringsteknik i en KVS förbättra förbättringen från slut till slut (dvs. ~2%). Dessutom påverkar sådan teknik i hög grad uppslagstiden som krävs av CPU: n för att hitta nyckeln och motsvarande värde i databasen, vilket minskar medeltiden med ~22, 5% och förbättrar 99th percentilen med ~62, 7%.

This thesis explores the role of open online educational resources as a tool for building longterm capacity for Sustainable Development planning. The focus is on energy and climate mitigation related to SDG 7 and 13. In particular the thesis explores medium to long term energy systems analysis and modelling - a critical activity for energy infrastructure development. An open teaching kit and online course for the Open Source energy Modelling System (OSeMOSYS) is presented. The OSeMOSYS teaching kit is derived from training and teaching experience on the use of the tool by the OpTIMUS community of practice and its partners. Several international organisations and consortium have long experience in carrying out capacity building initiatives and programmes in energy systems analysis and modelling across the globe. Yet, knowledge transfer, dissemination and application of newly learned tools are not as effective as they might be. Enabling conditions for sustained, effective and contentflexible long-term capacity building and teaching in energy systems analysis is necessary. Yet few accessible resources exist. Availability and access to open educational materials can contribute to the development of solid and long-term capacity, particularly in developing country contexts, which often rely on international support for such activities. The OSeMOSYS open educational resources, including the online course presented in this thesis, provide a ready-made example of an energy systems analysis course that can be directly deployed at higher education levels and in-house capacity building initiatives. Its open nature promotes and facilitates the development of a network of practitioners who can contribute back to the community. Users have the option of contributing to, using and reconfiguring materials and course examples of varying levels and specifics. These can then be shared and taken up by the community of practice. / Detta examensarbete utforskar rollen av öppet tillgängliga onlinebaserade material för inlärning och utlärning som ett verktyg för långvarande kunskap för hållbar utveckling och energiplanering. Fokuserande på energi och minskad klimatpåverkan i relation till hållbarhetsmålen 7 och 13. Mer specifikt utforskar examensarbetet medium till långvarig energisystemsanalys och energimodellering – en nyckelaktivitet för energiinfrastrukturutveckling. Ett öppet utlärnings-kit och onlinekurs för det öppna energimodelleringssystemet OSeMOSYS presenteras. OSeMOSYS utlärnings-kit är framtaget med hjälp av tidigare erfarenheter i utlärning av verktyget utfört av OpTIMUS Community of practice och partners. Flera internationella organisationer och konsortium har lång erfarenhet av att utföra kapacitetsuppbyggnads initiativ och program i energisystemsanalys och energimodellering världen över. Trots detta är kunskapsöverföring, spridning och applicering av nyligen inlärda verktyg inte lika effektiva som de kunnat vara. Att möjliggöra varaktig, effektiv och kontentflexibel långvarig kapacitetsuppbyggnad och utlärning av energisystemsanalys är nödvändigt. Tillgång och tillgänglighet till öppna pedagogiska material kan bidra till utvecklingen av hållbar långvarig kunskap, speciellt i ett utvecklingsland-perspektiv, vilka ofta är beroende av stöd från internationella organisationer för liknande aktiviteter. OSeMOSYS öppna pedagogiska resurser, inkluderande en onlinekurs presenterad i detta examensarbete, bidrar med ett färdigt exempel av en kurs i energisystemsanalys som är direkt applicerbar i högre utbildningsnivåer och landspecifika kapacitetsuppbyggnadsinitiativ. Dess öppna natur främjar och underlättar utvecklingen av ett nätverk av utövare vilka kan bidra tillbaka till samhället. Användare har möjlighet att bidra till, använda och ändra material och kursexempel i varierande svårighetsnivå och specifikt ämne. Dessa kan sedan spridas och tas upp av nätverket av användare för ytterligare samhällsnytta.

Introduction: Targeted pharmaceuticals for labelling with radio-isotopes for very specific imaging (and possibly later for targeted therapy) play a major role in Theranostics which is currently an important topic in Nuclear Medicine as well as personalised medicine. There was a need for a very specific lung cancer radiopharmaceutical that would specifically be uptaken in integrin 3 expression cells to image patients using a Positron Emission Tomography- Computed Tomography (PET-CT) scanner. Background and problem statement: Cold kits of c (RGDyK)–SCN-Bz-NOTA were kindly donated by Seoul National University (SNU) to help meet Steve Biko Hospital’s need for this type of imaging. These cold kits showed great results internationally in labelling with a 0.1 M 68Ge/68Ga generator (t1/2 of 68Ge and 68Ga are 270.8 days and 67.6 min, respectively). However the same cold kits failed to show reproducible radiolabeling with the 0.6 M generator manufactured under cGMP conditions at iThemba LABS, Cape Town and distributed by IDB Holland, the Netherlands. Materials and methods: There was therefore a need for producing an in-house NOTA-RGD kit that would enable production of clinical 68Ga-NOTA-RGD in high yields from the IDB Holland/iThemba LABS generator. Quality control included ITLC in citric acid to observe labelling efficiency as well as in sodium carbonate to evaluate colloid formation. HPLC was also performed at iThemba LABS as well as Necsa (South African Nuclear Energy Corporation). RGD was obtained from Futurechem, Korea. Kit mass integrity was determined by testing labelling efficiency of 10, 30 and 60 μg of RGD per cold kit. The RGD was buffered with sodium acetate trihydrate. The original kits were dried in a desiccator and in later studies only freeze dried. Manual labelling was also tested. The radiolabelled in-house kit’s ex vivo biodistribution in healthy versus tumour mice were examined by obtaining xenografts. The normal biodistribution was investigated in three vervet monkeys by doing PET-CT scans on a Siemens Biograph TP 40 slice scanner. Results: Cold kit formulation radiolabeling and purification methods were established successfully and SOPs (standard operating procedures) created. HPLC results showed highest radiochemical purity in 60 μg cold kit vials. 68Ga-NOTA-RGD showed increased uptake in tumours of tumour bearing mouse. The cold kit also showed normal distribution according to literature with fast blood clearance and excretion through kidneys into urine, therefore making it a suitable radiopharmaceutical for clinical studies. Conclusion: The in-house prepared cold kit with a 4 month shelf-life was successfully tested in mice and monkeys. / MSc (Pharmaceutics), North-West University, Potchefstroom Campus, 2014