O desenvolvimento da Medicina Nuclear, aliado à evolução dos equipamentos de diagnóstico e terapia, necessita, cada vez mais, da disponibilidade comercial de radioisótopos. Nesse contexto, o IPEN tem buscado atender e abastecer o mercado nacional. Um dos investimentos nesta área foi a aquisição de um ciclotron de 30 MeV, modelo Cyclone-30, que permitiu a produção dos radioisótopos tais como, o 18F, 67Ga, 201Tl e o 123I, sendo este último o foco do presente trabalho. Através de dados de produções rotineiras de 123I via irradiação com prótons em alvo gasoso de Xenônio com enriquecimento superior a 99,8% em 124Xe, foi realizado um estudo para identificar os fatores relevantes que influenciam diretamente o rendimento de obtenção de 123I com altíssimo grau de pureza. Embora a metodologia seja bem conhecida, quando se trata de produção comercial há uma escassez de dados sobre os parâmetros operacionais utilizados. Os parâmetros avaliados foram: pressão do gás 124Xe, intensidade de corrente de feixe de prótons, tempo de irradiação, temperatura de operação do sistema durante a irradiação, tempo de espera para formação de 123I, tempo de aquecimento do porta-alvo para recuperação do 123I formado, temperatura de aquecimento da solução de lavagem e influência do revestimento interno da câmara de irradiação com Ni. Com os resultados obtidos, foi possível alterar as condições operacionais nas produções rotineiras, conduzindo a um aumento de eficiência do processo em torno de 30%. / The development of diagnosis equipment and therapy procedures in nuclear medicine depends on the availability of commercial radioisotopes. IPEN is the most important institution that provides radioisotopes for national market. In order to achieve this function, IPEN had invested in the acquisition of a 30 MeV Cyclone-30 cyclotron to produce mainly 18F, 67Ga, 201Tl and 123I. The 123I production is the aim of the present work. With the 123I routine production data obtained by proton irradiation of Xe targets with an enrichment greater than 99.8%, it was possible to identify the important parameters that have direct influence on the production yield of high purity degree 123I. Even though the methodology for the commercial production of 123I, there are an scarcity of operational parameters data for this task. In this work the evaluated parameters were: 124Xe pressure, proton beam quality, irradiation time, operational temperature of the irradiation system under irradiation, waiting time to obtain 123I, temperature of washing solution and the impact of the internal Ni coating in the target. With the obtained results it was possible to modify the operational conditions for routine production and increasing the efficiency in about 30%.

O desenvolvimento da Medicina Nuclear, aliado à evolução dos equipamentos de diagnóstico e terapia, necessita, cada vez mais, da disponibilidade comercial de radioisótopos. Nesse contexto, o IPEN tem buscado atender e abastecer o mercado nacional. Um dos investimentos nesta área foi a aquisição de um ciclotron de 30 MeV, modelo Cyclone-30, que permitiu a produção dos radioisótopos tais como, o 18F, 67Ga, 201Tl e o 123I, sendo este último o foco do presente trabalho. Através de dados de produções rotineiras de 123I via irradiação com prótons em alvo gasoso de Xenônio com enriquecimento superior a 99,8% em 124Xe, foi realizado um estudo para identificar os fatores relevantes que influenciam diretamente o rendimento de obtenção de 123I com altíssimo grau de pureza. Embora a metodologia seja bem conhecida, quando se trata de produção comercial há uma escassez de dados sobre os parâmetros operacionais utilizados. Os parâmetros avaliados foram: pressão do gás 124Xe, intensidade de corrente de feixe de prótons, tempo de irradiação, temperatura de operação do sistema durante a irradiação, tempo de espera para formação de 123I, tempo de aquecimento do porta-alvo para recuperação do 123I formado, temperatura de aquecimento da solução de lavagem e influência do revestimento interno da câmara de irradiação com Ni. Com os resultados obtidos, foi possível alterar as condições operacionais nas produções rotineiras, conduzindo a um aumento de eficiência do processo em torno de 30%. / The development of diagnosis equipment and therapy procedures in nuclear medicine depends on the availability of commercial radioisotopes. IPEN is the most important institution that provides radioisotopes for national market. In order to achieve this function, IPEN had invested in the acquisition of a 30 MeV Cyclone-30 cyclotron to produce mainly 18F, 67Ga, 201Tl and 123I. The 123I production is the aim of the present work. With the 123I routine production data obtained by proton irradiation of Xe targets with an enrichment greater than 99.8%, it was possible to identify the important parameters that have direct influence on the production yield of high purity degree 123I. Even though the methodology for the commercial production of 123I, there are an scarcity of operational parameters data for this task. In this work the evaluated parameters were: 124Xe pressure, proton beam quality, irradiation time, operational temperature of the irradiation system under irradiation, waiting time to obtain 123I, temperature of washing solution and the impact of the internal Ni coating in the target. With the obtained results it was possible to modify the operational conditions for routine production and increasing the efficiency in about 30%.

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Submitted by Claudinei Pracidelli (cpracide@ipen.br) on 2015-12-10T17:38:32Z No. of bitstreams: 0 / Made available in DSpace on 2015-12-10T17:38:32Z (GMT). No. of bitstreams: 0 / Tese (Doutorado em Tecnologia Nuclear) / IPEN/T / Instituto de Pesquisas Energeticas e Nucleares - IPEN-CNEN/SP

Submitted by Claudinei Pracidelli (cpracide@ipen.br) on 2015-12-10T17:38:32Z No. of bitstreams: 0 / Made available in DSpace on 2015-12-10T17:38:32Z (GMT). No. of bitstreams: 0 / Neste trabalho foi desenvolvida uma nova metodologia de produção de iodo-125, que resultou na primeira produção deste radionuclídeo no Brasil. Cápsulas de alumínio foram projetadas, fabricadas e avaliadas para que suportassem condições de pressão, temperatura e fluxo de nêutrons no reator nuclear IEA-R1 do IPEN sem a ocorrência de liberação de material radioativo. Foram projetados, desenvolvidos e fabricados sistemas de carregamento, descarregamento e recuperação dos gases para a manipulação do gás xenônio e do iodo. Foi desenvolvido um novo método de lavagem da cápsula, para dissolução do iodo-125 adsorvido nas paredes, por meio de imersão em banho ultrassônico. Foram irradiadas três cápsulas no reator nuclear IEA-R1, por um período de aproximadamente 60 h contínuas, a um fluxo de nêutrons de 5,5 x 1013 n cm-2 s-1. Foi produzido um total de 13,53 GBq (365,73 mCi) de iodo-125, e o único contaminante encontrado foi o radionuclídeo iodo-126. Na análise radioquímica, pelo método de cromatografia em papel ascendente, o iodo-125 em solução de NaOH apresentou percentual de iodeto acima de 98%, superior à exigência da farmacopeia americana para soluções de iodo radioativo que é de 95%. Para a análise radionuclídica foi desenvolvida uma fonte planar, a base de resina epoxídica, para a contagem do iodo-125 em detector de germânio de alta pureza. A correlação entre o iodo-125 e o iodo-126 produzido apresentou valores entre 0,5 e 0,7% após um período de decaimento de 10 d, grau de pureza suficiente para a utilização em técnicas de radioimunoensaio. / Tese (Doutorado em Tecnologia Nuclear) / IPEN/T / Instituto de Pesquisas Energeticas e Nucleares - IPEN-CNEN/SP

Molecular biology has entered an era of systematic and automated experimentation. High-throughput techniques have moved biology from small-scale experiments focused on specific genes and proteins to genome and proteome-wide screens. One result of this endeavor is the compilation of complex networks of interacting proteins. Molecular biologists hope to understand life's complex molecular machines by studying these networks. This thesis addresses tree open problems centered upon their analysis and quality assessment. First, we introduce power graph analysis as a novel approach to the representation and visualization of biological networks. Power graphs are a graph theoretic approach to lossless and compact representation of complex networks. It groups edges into cliques and bicliques, and nodes into a neighborhood hierarchy. We demonstrate power graph analysis on five examples, and show its advantages over traditional network representations. Moreover, we evaluate the algorithm performance on a benchmark, test the robustness of the algorithm to noise, and measure its empirical time complexity at O (e1.71)- sub-quadratic in the number of edges e. Second, we tackle the difficult and controversial problem of data quality in protein interaction networks. We propose a novel measure for accuracy and completeness of genome-wide protein interaction networks based on network compressibility. We validate this new measure by i) verifying the detrimental effect of false positives and false negatives, ii) showing that gold standard networks are highly compressible, iii) showing that authors' choice of confidence thresholds is consistent with high network compressibility, iv) presenting evidence that compressibility is correlated with co-expression, co-localization and shared function, v) showing that complete and accurate networks of complex systems in other domains exhibit similar levels of compressibility than current high quality interactomes. Third, we apply power graph analysis to networks derived from text-mining as well to gene expression microarray data. In particular, we present i) the network-based analysis of genome-wide expression profiles of the neuroectodermal conversion of mesenchymal stem cells. ii) the analysis of regulatory modules in a rare mitochondrial cytopathy: emph{Mitochondrial Encephalomyopathy, Lactic acidosis, and Stroke-like episodes} (MELAS), and iii) we investigate the biochemical causes behind the enhanced biocompatibility of tantalum compared with titanium.

Tesis (para optar al grado de magíster en derecho mención derecho penal) / Por medio del presente trabajo, se pretende plantear un problema y dar una respuesta en cuanto a poder afirmar que la norma del articulo 136 de la Ley General de Pesca y Acuicultura, de verificarse, ya sea a modo de acción u omisión y que las mismas sean a titulo doloso y/o culposo, en su caso, trátase de una figura infraccional sancionada solo en sede civil a la luz de lo dispuesto en el articulo 124 del citado cuerpo legal o por el contrario, teniendo en consideración las sanciones a imponer en su caso, ya sea la sanción de multa y/o la pena privativa de libertad, dicha figura es realmente un tipo penal independiente que debe ser investigada y resuelta en sede penal. Asimismo, de afirmarse que el Art. 136 del cuerpo legal citado es efectivamente una figura delictual, un delito independiente, plantear la problemática si este ilícito penal tratase de un delito de peligro o un delito de lesión, de resultado, teniendo en consideración al momento de la determinación de la sanción penal el principio de lesividad en materia penal. Asimismo, en caso de operar la reparación del daño producido por el actuar ilícito, si esa reparación trae aparejada alguna consecuencia favorable para el autor al momento de la sanción o pena a imponer

Background: Boron Neutron Capture Therapy (BNCT) is a binary approach to cancer therapy that requires accumulation of boron atoms preferentially in tumour cells. This can be achieved by using nanoparticles as boron carriers and taking advantage of the enhanced permeability and retention (EPR) effect. Here, we present the preparation and characterization of size and shape-tuned gold NPs (AuNPs) stabilised with polyethylene glycol (PEG) and functionalized with the boron-rich anion cobalt bis(dicarbollide), commonly known as COSAN. The resulting NPs were radiolabelled with 124I both at the core and the shell, and were evaluated in vivo in a mouse model of human fibrosarcoma (HT1080 cells) using positron emission tomography (PET). Methods: The thiolated COSAN derivatives for subsequent attachment to the gold surface were synthesized by reaction of COSAN with tetrahydropyran (THP) followed by ring opening using potassium thioacetate (KSAc). Iodination on one of the boron atoms of the cluster was also carried out to enable subsequent radiolabelling of the boron cage. AuNPs grafted with mPEG-SH (5 Kda) and thiolated COSAN were prepared by ligand displacement. Radiolabelling was carried out both at the shell (isotopic exchange) and at the core (anionic absorption) of the NPs using 124I to enable PET imaging. Results: Stable gold nanoparticles simultaneously functionalised with PEG and COSAN (PEG-AuNPs@[4]) with hydrodynamic diameter of 37.8 0.5 nm, core diameter of 19.2 1.4 nm and -potential of 18.0 0.7 mV were obtained. The presence of the COSAN on the surface of the NPs was confirmed by Raman Spectroscopy and UV-Vis spectrophotometry. PEG-AuNPs@[4] could be efficiently labelled with 124I both at the core and the shell. Biodistribution studies in a xenograft mouse model of human fibrosarcoma showed major accumulation in liver, lungs and spleen, and poor accumulation in the tumour. The dual labelling approach confirmed the in vivo stability of the PEG-AuNPs@[4]. Conclusions: PEG stabilized, COSAN-functionalised AuNPs could be synthesized, radiolabelled and evaluated in vivo using PET. The low tumour accumulation in the animal model assayed points to the need of tuning the size and geometry of the gold core for future studies.

The major aims of this paper are to present how we can improve the students understanding and involvement in mathematics by using a programming/graphic calculator. I will use differentials as examples such as differentiation ,integrals and differential equations, creating lines of slopes for differential equation of the type y’= f(x,y) . Find the solution of some differential equations by using regression and create the graph connected to the differential equation. As we have different approaches to solving a problem, it is a hope the students interest in mathematics will improve. The tools used will be programming, graphic commands as plot, f-line, etc. One goal is also to show how we can create small programs solving problems in mathematics. For many students this will be a stepping stone for further work with programming. The programs used can be copied using the program FA 124 that can be downloaded from Casios homepages. On request I can send you the programs.

The major aims of this paper are to present how we can improve the students understanding and involvement in mathematics by using a programming/graphic calculator. I will use differentials as examples such as differentiation ,integrals and differential equations, creating lines of slopes for differential equation of the type y’= f(x,y) . Find the solution of some differential equations by using regression and create the graph connected to the differential equation. As we have different approaches to solving a problem, it is a hope the students interest in mathematics will improve. The tools used will be programming, graphic commands as plot, f-line, etc. One goal is also to show how we can create small programs solving problems in mathematics. For many students this will be a stepping stone for further work with programming. The programs used can be copied using the program FA 124 that can be downloaded from Casios homepages. On request I can send you the programs.