Submitted by Claudinei Pracidelli (cpracide@ipen.br) on 2014-12-19T16:34:27Z No. of bitstreams: 0 / Made available in DSpace on 2014-12-19T16:34:27Z (GMT). No. of bitstreams: 0 / Tese (Doutorado em Tecnologia Nuclear) / IPEN/T / Instituto de Pesquisas Energeticas e Nucleares - IPEN-CNEN/SP

Made available in DSpace on 2014-10-09T12:53:04Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T13:58:24Z (GMT). No. of bitstreams: 0 / Análogos da timidina têm sido marcados com diferentes radioisótopos devido ao seu potencial em monitorar a proliferação incontrolável de células. Considerando que o radioisótopo tecnécio-99m mantém ainda uma posição privilegiada devido às suas propriedades químicas e nucleares, este trabalho constituiu-se do desenvolvimento de uma nova técnica de marcação da timidina com o 99mTc, mediante o emprego de complexos organometálicos. Os objetivos do trabalho foram: a síntese do complexo organometálico carbonil-tecnécio-99m; marcação da timidina com este complexo precursor; avaliação da estabilidade; e avaliações radioquímicas e biológicas com animais sadios e portadores de tumor. A preparação do complexo precursor, utilizando o gás CO foi de fácil execução, assim como a marcação da timidina com este precursor, obtendo-se uma pureza radioquímica ≥ 97% e ≥ 94%, respectivamente. Sistemas cromatográficos com bons níveis de confiabilidade foram utilizados, podendo qualificar e quantificar as espécies radioquímicas. O resultado do estudo in vitro da lipofilicidade revelou que o a timidina radiomarcada é hidrofílica, com um coeficiente de partição (log P) de -1,48. O complexo precursor e a timidina radiomarcada apresentaram boa estabilidade radioquímica em até 6 h em temperatura ambiente. A estabilidade com soluções de cisteína e histidina apresentaram perdas entre oito e onze pontos percentuais para concentrações de até 300 mM. Os ensaios de biodistribuição em camundongos sadios indicaram que a timidina radiomarcada apresentou uma rápida depuração sangüínea e baixa captação nos demais órgãos, com predominância de excreção da droga pelo sistema urinário e hepatobiliar. A captação tumoral foi baixa, apresentando valores de 0,28 e 0,18 %DI/g para tumor de pulmão e mama, respectivamente. Os resultados obtidos sugerem mais investigações em outros modelos tumorais ou a modificação da estrutura da molécula orgânica que atua como ligante. / Dissertação (Mestrado) / IPEN/D / Instituto de Pesquisas Energeticas e Nucleares - IPEN/CNEN-SP

Made available in DSpace on 2014-10-09T12:50:36Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T13:58:59Z (GMT). No. of bitstreams: 1 00565.pdf: 1667046 bytes, checksum: 30ae0de467544ad54ff6c49ca78bbf92 (MD5) / Dissertacao (Mestrado) / IEA/D / Instituto de Biociencias, Universidade de Sao Paulo - IB/USP

Submitted by Claudinei Pracidelli (cpracide@ipen.br) on 2014-12-19T16:34:27Z No. of bitstreams: 0 / Made available in DSpace on 2014-12-19T16:34:27Z (GMT). No. of bitstreams: 0 / Tumores carcinoides (neoplasias bem diferenciadas) são tumores neuroendócrinos que podem surgir em diferentes locais anatômicos. Na população a prevalência dos tumores carcinoides é de aproximadamente 10 casos para um milhão de habitantes e sua incidência é maior na quinta e sexta década de vida. Este trabalho propõe um modelo cinético baseado na teoria da análise compartimental em humanos com tumores carcinoides que se submeterão ao tratamento com o radiofármaco [177Lu-DOTA0,Tyr3]Octreotato. Imagens cintilográficas dinâmicas planares, obtidas imediatamente à injeção de 370 MBq (10 mCi) do radiofármaco, foram obtidas com o tomógrafo SPECT (Single Photon Emission Computed Tomography). Por meio da seleção de regiões de interesse (ROI) os resultados foram digitalizados e aplicados ao modelo cinético aqui proposto. A primeira fase do estudo (atividade de 370 MBq) teve como objetivo conhecer os parâmetros cinéticos e subsequentemente, o paciente foi submetido ao protocolo de tratamento radioterápico, a critério médico, aos quatro ciclos de 7,4 GBq (200 mCi) do radiofármaco. Desta forma, foi possível estimar previamente as constantes cinéticas ki,j da biodistribuição do 177Lu-DOTATATO no corpo, sendo ki,j a fração de transferência do i-ésimo compartimento (tecido ou órgão) para o j-ésimo compartimento a partir das ROI demarcadoras dos órgãos de maior captação, a saber: fígado, rins, região vascularizada e tumores carcinoides. A partir das constantes cinéticas ki,j a estimativa de dose absorvida em 26 órgãos foi estimada pelo método MIRD. Os resultados dosimétricos foram compatíveis com outras metodologias descritas na literatura. Para um paciente adulto de 73,6 kg, em termos médios seus rins (sem os protetores renais) recebem a maior intensidade de dose (2,39 mGy/MBq) seguido do fígado (0,70 mGy/MBq). Observou-se que tumores com aproximadamente 100g recebem dose da ordem de 0,52 mGy/MBq independentemente da posição a que se encontram no corpo. Este achado se deve à predominância do dano devido às partículas beta quando comparado à radiação gama que possui pouco rendimento de emissão no processo de decaimento do 177Lu. Portanto, os parâmetros cinéticos que promovem a captação do 177Lu nas células são os principais responsáveis pela composição da dose no tumor e demais órgãos. / Tese (Doutorado em Tecnologia Nuclear) / IPEN/T / Instituto de Pesquisas Energeticas e Nucleares - IPEN-CNEN/SP

In this thesis, we demonstrate how presheaves of labelled transition systems (LTS) acquire a very natural form of spatially induced independence on their actions when we allow a minimal amount of gluing on selected transitions within such systems. This gluing condition is characterized in the new model of LTS-adapted presheaf, and we also make use of the new model of asynchronous labelled transition system with equivalence (ALTSE) to characterize independence on actions. As such, our main result, the Theorem of Spatially Induced Independence, establishes functors from the categories of LTS-adapted presheaves to the categories of ALTSE-valued presheaves; it is a result that extends a proposition of Malcolm [SSTS] in the context of LTS-valued sheaves on complete Heyting algebras.

Urokinase-type plasminogen activator (uPA) protein is a serine protease of the trypsin family that is overexpressed by tumors cells seeking to metastasize. Molecular imaging methods using molecular imaging probe designed to target uPA could provide a method for the detection of aggressive cancers and monitoring response to treatment. Four classes of high affinity uPA inhibitors, three which were reversible and one irreversible, were used as platforms to develop radiolabeled probes for uPA. Based on structure-activity relationships, lead compounds were modified to allow for the introduction of a radiohalogen (radioiodine) at different sites in the corresponding molecules. Suitable synthetic strategies were developed to create libraries of iodinated phenyl guanidine, peptide, naphtamidine and phosphonate derivatives. For the phenylguanidines colorimetric assays showed the product had micromolar affinity while for the peptide derivatives low nanomolar affinity for the iodinated analogue was observed (1.4 nM to 2.53 nM). Unfortunately quantitative biodistribution studies showed low tumour uptake (<0.5% ID/g). More promising results were obtained for the irreversible iodinated phosphonated derivative which had an affinity of 2.1 nM. This reagent showed 1.95% ID/g tumour uptake and lower blood uptake in vivo which demonstrates advantageous properties over existing uPA probes in terms of tumour-to-blood ratios. A complementary development was also achieved in that the first example of a 125I-labelled tetrazine was prepared. This new reagent can be used in pre-targeted strategies that utilize bioorthogonal coupling between stained trans-cyclooctene (TCO) and tetrazines. The product was prepared using a concomitant oxidation iodo-destannylation reaction and the product isolated in 80% radiochemical yield. The reaction with transcycloctene proceeded rapidly to produce various isomers which were fully characterized through NMR analysis of the non-radioactive analogues. / Thesis / Doctor of Philosophy (PhD)

Yes / In advanced manufacturing systems, the production of complex and highly customisable products requires the preparation of many different product specifications and associated manufacturing process plans. The creation of these plans involves the search for the production resources (e.g. robots, machine tools, inspection devices) that are needed to implement the product specifications and how to orchestrate them. We present a model-based approach to the automatic generation of manufacturing process plans from the models of the target products and available resources. The modelling language is based on labelled transition systems, which are useful to represent sequences of operations that can be executed in parallel by multiple production resources. Some preliminary experimental results demonstrate the feasibility of the presented approach. / This conference paper will be released for public view at the end of the publisher embargo on 19 May 2025.

Thesis (MMed)--Stellenbosch University, 2014. / ENGLISH ABSTRACT: Background Occult blood loss from the gastrointestinal tract (GIT), causing iron deficiency often with anaemia, can be diagnostically and therapeutically challenging. This is because the endoscopic and radiologic tests may be negative due to the slow, chronic and intermittent nature of the gastrointestinal bleeding, making timing key in detection and localisation of the bleed. These limitations can be approached using two different radioactive isotopes. Firstly, we tested the sensitivity of extending Cr-51 RBC for 21 days relative to 5 days to detect GIT bleeding and its use to optimise timing of a Tc-99m RBC study for GIT blood loss localisation. Finally, we tested if the information provided by the Tc-99m RBC study aided gastroenterologic intervention for anatomical localisation of a lesion. Method In this retrospective review, after obtaining institutional and ethics committee approval, records of patients referred for evaluation of possible GIT blood loss were reviewed. In each; daily appearance of radiochromium in stool was measured in the whole body counter. In those cases exceeding 50 ml/day, a technetium-99m (Tc-99m) localization study was performed. These studies were correlated with clinical findings. Results A total of 59 Cr-51 RBC studies were carried out in 36 females and 21 males (n = 57). In 32 (54%) the radiochromium results were positive with 75% of the bleeding incidences occurring after 5 days of stool collection. Of 17 cases in whom Tc-99m RBC imaging studies were performed, 14 (82%) were positive with specific anatomical sites successfully defined in twelve. In all patients with blood loss of >100 ml/24h, Tc-99m RBC were positive and localised. Ten of the 17 Tc-99m RBC studies were further investigated and half diagnosed with small-bowel angiodysplasia. Conclusion This sequential twin isotope method is practical in revealing otherwise silent intestinal haemorrhage. Although it has good patient acceptability and clinical as well as diagnostic utility in management, further studies are required to clearly establish a cut-off level of blood loss for performing imaging studies and the impact of the findings on the overall patient management. / AFRIKAANSE OPSOMMING: Agtergrond Die evaluasie van okkulte bloedverlies uit die gastro-intestinale kanaal (GIT), met gevolglike ystertekort anemie, kan diagnosties en terapeuties uitdagend wees. Dit is omdat endoskopiese en radiologiese ondersoeke negatief mag wees as gevolg van die stadige, chroniese en intermitterende aard van die gastro-intestinale bloeding, wat die presiese tydstip van opsporing en lokalisering van die bloeding krities belangrik maak. Hierdie beperkings kan aangespreek word deur twee verskillende radioaktiewe isotope te gebruik. Eerstens is die sensitiwiteit van die verlenging van die Cr-51 RBS studie tot 21 dae in plaas van 5 dae om die GIT bloeding op te spoor, getoets, asook die gebruik daarvan om die optimale tyd vir ‘n Tc-99m RBS studie om die GIT bloedverlies te lokaliseer, vas te stel. Laastens is getoets of die inligting van die Tc-99m RBS studie wel bygedra het tot die gastroenterologiese ingreep om die letsel anatomies te lokaliseer. Metode Na institusionele en etiese komitee toestemming is inligting van pasiënte wat vir die evaluering van ‘n moontlike GI bloedverlies verwys is, in hierdie retrospektiewe oorsig nagegaan. Die daaglikse voorkoms van radioaktiewe chroom in stoelgangmonsters is in ‘n heelliggaamteller gemeet. In gevalle waar dit 50 ml/dag oorskry het, is ‘n tegnesium 99m (Tc 99m) studie gedoen. Hierdie studies is met die kliniese bevindinge gekorreleer. Resultate ‘n Totaal van 59 Cr-51 RBS studies is in 36 vroue en 21 mans (n = 57) gedoen. Die gemerkte chroomstudies was positief in 32 (54%), met 75% van die bloedings wat meer as 5 dae na versameling van die stoelgang plaasgevind het. In veertien (82%) van die 17 gevalle waar Tc-99m RBS studies gedoen is, was die studies positief. Spesifieke anatomiese gebiede van bloeding kon in 12 hiervan suksesvol bevestig word. Tc-99m RBS studies was positief in al die pasiënte met ‘n bloedverlies van >100 ml/24h, en kon gelokaliseer word. Tien van die 17 Tc-99m RBS studies is verder ondersoek en die helfte daarvan gediagnoseer met dunderm angiodisplasie. Gevolgtrekking Die opeenvolgende twee isotoopmetode om andersins asimptomatiese dermbloeding op te spoor, is prakties uitvoerbaar. Alhoewel die studies goed deur pasiënte aanvaar is, en ook van kliniese en diagnostiese waarde in die hantering van die pasiënte is, is verdere studies nodig om die afsnypunt vir die hoeveelheid bloedverlies om beeldingstudies uit te voer, sonder twyfel vas te stel, asook om die impak van die bevindings op ‘n groter pasiëntpopulasie vas te stel.

Thesis (PhD)--Stellenbosch University, 2015. / ENGLISH ABSTRACT : In this thesis, a number of combinatorial objects are enumerated. Du and Yin as well as Shin and Zeng (by a different approach) proved an elegant formula for the number of labelled trees with respect to a given in degree sequence, where each edge is oriented from a vertex of lower label towards a vertex of higher label. We refine their result to also take the number of sources (vertices of in degree 0) or sinks (vertices of out degree 0) into account. We find formulas for the mean and variance of the number of sinks or sources in these trees. We also obtain a differential equation and a functional equation satisfied by the generating function for these trees. Analogous results for labelled trees with two marked vertices, related to functional digraphs, are also established. We extend the work to count reachable vertices, sinks and leaf sinks in these trees. Among other results, we obtain a counting formula for the number of labelled trees on n vertices in which exactly k vertices are reachable from a given vertex v and also the average number of vertices that are reachable from a specified vertex in labelled trees of order n. In this dissertation, we also enumerate certain families of set partitions and related tree-like structures. We provide a proof for a formula that counts connected cycle-free families of k set partitions of {1, . . . , n} satisfying a certain coherence condition and then establish a bijection between these families and the set of labelled free k-ary cacti with a given vertex-degree distribution. We then show that the formula also counts coloured Husimi graphs in which there are no blocks of the same colour that are incident to one another. We extend the work to count coloured oriented cacti and coloured cacti. Noncrossing trees and related tree-like structures are also considered in this thesis. Specifically, we establish formulas for locally oriented noncrossing trees with a given number of sources and sinks, and also with given indegree and outdegree sequences. The work is extended to obtain the average number of reachable vertices in these trees. We then generalise the concept of noncrossing trees to find formulas for the number of noncrossing Husimi graphs, cacti and oriented cacti. The study is further extended to find formulas for the number of bicoloured noncrossing Husimi graphs and the number of noncrossing connected cycle-free pairs of set partitions. / AFRIKAANSE OPSOMMING : In hierdie tesis word ’n aantal kombinatoriese objekte geenumereer. Du en Yin asook Shin en Zeng (deur middel van ’n ander benadering) het ’n elegante formule vir die aantal geëtiketteerde bome met betrekking tot ’n gegewe ingangsgraadry, waar elke lyn van die nodus met die kleiner etiket na die nodus met die groter etiket toe georiënteer word. Ons verfyn hul resultaat deur ook die aantal bronne (nodusse met ingangsgraad 0) en putte (nodusse met uitgangsgraad 0) in ag te neem. Ons vind formules vir die gemiddelde en variansie van die aantal putte of bronne in hierdie bome. Ons bepaal verder ’n differensiaalvergelyking en ’n funksionaalvergelyking wat deur die voortbringende funksie van hierdie bome bevredig word. Analoë resultate vir geëtiketteerde bome met twee gemerkte nodusse (wat verwant is aan funksionele digrafieke), is ook gevind. Ons gaan verder voort deur ook bereikbare nodusse, bronne en putte in hierdie bome at te tel. Onder andere verkry ons ’n formule vir die aantal geëtiketteerde bome met n nodusse waarin presies k nodusse vanaf ’n gegewe nodus v bereikbaar is asook die gemiddelde aantal nodusse wat bereikbaar is vanaf ’n gegewe nodus. Ons enumereer in hierdie tesis verder sekere families van versamelingsverdelings en soortgelyke boom-vormige strukture. Ons gee ’n bewys vir ’n formule wat die aantal van samehangende siklus-vrye families van k versamelingsverdelings op {1, . . . , n} wat ’n sekere koherensie-vereiste bevredig, en ons beskryf ’n bijeksie tussen hierdie familie en die versameling van geëtiketteerde vrye k-êre kaktusse met ’n gegewe nodus-graad-verdeling. Ons toon ook dat hierdie formule ook gekleurde Husimi-grafieke tel waar blokke van dieselfde kleur nie insident met mekaar mag wees nie. Ons tel verder ook gekleurde georiënteerde kaktusse en gekleurde kaktusse. Nie-kruisende bome en soortgelyke boom-vormige strukture word in hierdie tesis ook beskou. On bepaal spesifiek formules vir lokaal georiënteerde nie-kruisende bome wat ’n gegewe aantal bronne en putte het asook nie-kruisende bome met gegewe ingangs- en uitgangsgraadrye. Ons gaan voort deur die gemiddelde aantal bereikbare nodusse in hierdie bome te bepaal. Ons veralgemeen dan die konsep van nie-kruisende bome en vind formules vir die aantal nie-kruisende Husimi-grafieke, kaktusse en georiënteerde kaktusse. Laastens vind ons ’n formule vir die aantaal tweegekleurde nie-kruisende Husimi-grafieke en die aantal nie-kruisende samehangende siklus-vrye pare van versamelingsverdelings.

In this thesis we examine the relationship between hypersequent and some types of labelled sequent calculi for a subset of intermediate logics—logics between intuitionistic (Int), and classical logics—that have geometric Kripke semantics, which we call Int∗/Geo. We introduce a novel calculus for a fragment of first-order classical logic, which we call partially-shielded formulae (or PSF for short), that is adequate for expressing the semantic validity of formulae in Int∗/Geo, and apply techniques from correspondence theory to provide translations of hypersequents, simply labelled sequents and relational sequents (simply labelled sequents with relational formulae) into PSF. Using these translations, we show that hypersequents and simply labelled sequents for calculi in Int∗/Geo share the same models. We also use these translations to justify various techniques that we introduce for translating simply labelled sequents into relational sequents and vice versa. In particular, we introduce a technique called "transitive unfolding" for translating relational sequents into simply labelled sequents (and by extension, hypersequents) which preserves linear models in Int∗/Geo. We introduce syntactic translations between hypersequent calculi and simply labelled sequent calculi. We apply these translations to a novel hypersequent framework HG3ipm∗ for some logics in Int∗/Geo to obtain a corresponding simply labelled sequent framework LG3ipm∗, and to an existing simply labelled calculus for Int from the literature to obtain a novel hypersequent calculus for Int. We introduce methods for translating a simply labelled sequent calculus into a cor- responding relational calculus, and apply these methods to LG3ipm∗ to obtain a novel relational framework RG3ipm∗ that bears similarities to existing calculi from the literature. We use transitive unfolding to translate proofs in RG3ipm∗ into proofs in LG3ipm∗ and HG3ipm∗ with the communication rule, which corresponds to the semantic restriction to linear models.