Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The granulocyte-macrophage colony stimulating factor (GM-CSF) is a cytokine that regulates the proliferation and differentiation of hematopoietic progenitor cells and activates mature granulocytes and macrophages. Clinically is used in enhancing hematopoietic recovery after cancer chemotherapy and bone marrow transplantation. A reversed-phase liquid chromatography (RP-LC) method was validated for the determination of the non-glycosylated recombinant rhGM-CSF (Molgramostim) in biopharmaceutical formulations. The RP-LC method was carried out on a Jupiter C4 column (250 mm x 4.6 mm i.d.), maintained at 45 ºC. The mobile phase A consisted of 0.1% TFA and the mobile phase B consisted of 0.1% TFA in acetonitrile, run at a gradient from: 0.01 34 min, 37% 50% of B; 34 35 min linear back to 37% of B and 35 40 min, 37% of B. The flow rate was 1 mL/min, and using photodiode array (PDA) detection at 214 nm. The chromatographic separation was obtained with the retention time of 29.2 min, and was linear over the concentration range of 2-300 μg/mL (r2 = 0.9992). The procedure was validated evaluating parameters such as the specificity, linearity, precision, accuracy, robustness, limit of detection and limit of quantitation. The specificity was proven through degradation studies, showing that also there was no interference of the excipients. Moreover, the in vitro cytotoxicity test of the degraded products showed significant differences (p<0.05). The proposed method was applied for the analysis of molgramostim and their related proteins, and the results were correlated to the bioassay, showing mean differences of the potency 1.02% higher for the RP-LC method, contributing to establish alternatives to characterize and monitoring its instability, improving the quality control and assuring the therapeutic efficacy. / O fator estimulador da colônia de granulócitos e macrófagos (GM-CSF) é uma citocina que regula a proliferação e diferenciação de células progenitoras hematopoiéticas e ativa granulócitos e macrófagos maduros. É clinicamente indicado após quimioterapia para o câncer e após transplante de medula óssea. No presente trabalho foi validado método por cromatografia líquida em fase reversa (CL-FR) para a avaliação da molgramostima, forma recombinante não-glicosilada do GM-CSF, em formulação biofarmacêutica. Utilizou-se coluna Júpiter C4 (250 mm x 4,6 mm d.i.), mantida a 45 °C. A fase móvel A foi composta de ácido trifluoracético 0,1% e a fase móvel B de ácido trifluoracético 0,1% em acetonitrila, eluídas no gradiente: 0,01 34 min, 37 50% de B; 34 35 min, 50 37% de B, mantendo-se nesta proporção até 40 min. Utilizou-se vazão de 1 mL/min, usando detector de arranjo de diodos (DAD) a 214 nm. A separação cromatográfica foi obtida no tempo de 29,2 min, sendo linear na faixa de concentração de 2 300 μg/mL (r2 = 0,9992). O procedimento foi validado, avaliando-se os parâmetros de especificidade, linearidade, precisão, exatidão, robustez, limite de detecção e quantificação. A especificidade foi comprovada através de estudos de degradação, demonstrando também que não houve interferência dos excipientes. Além disso, realizou-se o teste de citotoxicidade in vitro dos produtos degradados que apresentaram diferença significativa (p<0,05). O método foi aplicado para avaliação de potência de molgramostima e de proteínas relacionadas, e os resultados foram correlacionados com o bioensaio, observando-se diferenças médias de potência 1,02% superiores por CL-FR. Contribuiu-se assim para o estabelecimento de alternativas que aprimoram o controle da qualidade, garantindo a segurança e eficácia terapêutica.

A combinação entre o delapril (DEL), um inibidor da enzima conversora de angiotensina e o manidipino (MAN), um antagonista dos canais de cálcio, produz um efeito anti-hipertensivo sinérgico, podendo ser considerado um ótimo tratamento para pacientes com hipertensão essencial leve e moderada. No presente trabalho foram desenvolvidos e validados métodos cromatográfico e eletroforético para avaliação simultânea de DEL e MAN em produto farmacêutico. As análises por cromatografia líquida em fase reversa (CL-FR) foram executadas utilizando coluna C8 (250 mm x 4,6 mm), mantida a 35 oC. A fase móvel foi constituída por acetonitrila e solução de trietilamina 0,3%, pH 3,0 (55:45; v/v), eluída na vazão de 1,2 mL/min com detecção a 220 nm. Paralelamente, desenvolveu-se método por eletroforese capilar, utilizando modo de separação por cromatografia eletrocinética micelar (MEKC) e ácido salicílico como padrão interno. Foi utilizado capilar de sílica fundida (comprimento efetivo de 72 cm) mantido a 35 °C, com solução eletrolítica composta de tampão borato 50 mM e dodecil sulfato de sódio (SDS) 5 mM, pH 9,0. Voltagem de 25 kV foi aplicada e a injeção foi de 50 mbar durante 5 s, com detecção a 208 nm. A especificidade e a capacidade dos métodos serem indicativos de estabilidade foram demonstradas através de estudos de degradação forçada dos fármacos e pela não interferência dos excipientes nas análises. Além disso, o desenho experimental Plackett-Burman foi utilizado para a avaliação da robustez, observando-se resultados adequados para ambos métodos. Os procedimentos foram validados de acordo com guias aceitos internacionalmente, observando-se resultados em uma faixa aceitável. Os métodos propostos foram aplicados com sucesso na determinação quantitativa simultânea de DEL e MAN em comprimidos, não havendo diferença significativa dos resultados (P>0,05), contribuindo, portanto, para aprimorar o controle da qualidade, assegurando a eficácia terapêutica. / The combination of delapril (DEL), an angiotensin converting enzyme inhibitor and manidipine (MAN), an antagonist of calcium channels, produces a synergic antihypertensive effect and may be regarded as an optimal antihypertensive drug treatment in mild to moderate essential hypertensive patients. The chromatographic and eletrophoretic methods for the simultaneous evaluation of DEL and MAN in pharmaceutical product were developed and validated in the present work. The reversed-phase liquid chromatography (RP-LC) method was carried out on a C8 column (250 mm x 4.6 mm i.d., 5 μm), maintained at 35 ºC. The mobile-phase consisted of acetonitrile and a solution of triethylamine 0.3% pH 3.0 (55:45; v/v), running at a flow rate of 1.2 mL/min, with detection at 220 nm. The capillary electrophoresis method was developed using the micellar electrokinetic chromatography (MEKC) as the separation mode, and salicylic acid as internal standard. The analysis were performed on a fused-silica capillary (effective length of 72 cm) maintained at 35 °C, with 50 mM of borate buffer and 5 mM of sodium dodecyl sulfate (SDS) at pH 9.0 as background electrolyte. The separation was achieved at 25 kV applied voltage and the injection was performed at 50 mbar for 5 s, with detection at 208 nm. The specificity and stability-indicating capability of the methods were demonstrated through forced degradation studies, which also show that there is no interference of the excipients in the analysis. Moreover, the Plackett- Burman experimental design was used for robustness evaluation, giving acceptable results for both methods. The procedures were validated according to Internationals guidelines, giving results within the acceptable range. Therefore, the proposed methods were successfully applied for the simultaneous quantitative analysis of DEL and MAN in the tablet dosage form, showing non-significant difference (P>0.05), contributing to improve the quality control and to assure the therapeutic efficacy.

Orientador: Isabel Cristina Sales Fontes Jardim / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Química / Made available in DSpace on 2018-08-18T09:12:26Z (GMT). No. of bitstreams: 1 Segato_MilenaPinotti_D.pdf: 2442383 bytes, checksum: e69a88b2ce9ec4c5ba2780755d0a6c2f (MD5) Previous issue date: 2011 / Resumo: Este trabalho descreve o desenvolvimento de novas fases estacionárias (FE) sorvidas e imobilizadas para cromatografia líquida de alta eficiência em fase reversa (CLAE-FR), utilizando-se suporte de sílica não modificada e metalizada com zircônia, recobertos com o polímero poli(dimetilsiloxano-co-metilfenilsiloxano) (PDMFS). O processo de imobilização do polímero foi feito por tratamento térmico e as condições que forneceram FE com o melhor desempenho cromatográfico foram 140 ºC e 6 h. As FE preparadas sob estas condições apresentaram porcentagens de carbono entre 10 e 11 % e espessura de camada entre 0,6 e 0,7 nm. Foi feito o capeamento das FE buscando-se um melhor recobrimento dos sítios ativos do suporte e, após este procedimento, houve um aumento de cerca de 2 % na porcentagem de carbono e redução do número de silanóis livres e vicinais nos suportes cromatográficos. A caracterização físico-química das FE sugere que o PDMFS está fisicamente adsorvido e quimicamente ligado aos suportes, sendo que as interações com o suporte metalizado são mais intensas. As FE foram avaliadas cromatograficamente por meio da separação de algumas misturas teste e seus desempenhos foram similares aos de colunas comerciais tradicionais, com eficiências superiores a 70000 pratos m para o acenafteno, nas FE não capeadas, e acima de 56000 pratos m nas FE capeadas. As características cromatográficas das FE preparadas foram similares no que diz respeito às seletividades hidrofóbica, estérica e aromática. As FE capeadas apresentaram maior hidrofobicidade e menor capacidade de formação de ligações de hidrogênio que as FE não capeadas. A zirconização aumentou a acidez dos sítios ativos e a capacidade de troca iônica das sílicas zirconizadas. Por outro lado, a combinação da zirconização do suporte com o capeamento é uma estratégia importante para a obtenção de FE com estabilidade elevada. As FE desenvolvidas neste trabalho apresentam potencial para serem aplicadas na separação de compostos aromáticos de diferentes polaridades, agrotóxicos e fármacos contendo grupos básicos / Abstract: This work describes the development of new stationary phases (SP) based on poly(dimethylsiloxane-co-methylphenylsiloxane) sorbed and immobilized onto silica and zirconized silica for reversed phase high performance liquid chromatography. The polymer was immobilized by thermal treatment at 140 °C during 6 h, which were the conditions that produced SP with the best chromatographic performance. The SP prepared using these conditions presented carbon loadings between 10 and 11 % and polymeric thicknesses between 0.6 and 0.7 nm. The SP were end-capped aiming at a better coverage of the active sites of the support. This procedure increased the carbon loadings by about 2 % and reduced the number of free and vicinal silanols on the chromatographic supports. Physico-chemical characterization of the SP suggests that PDMFS is physically absorbed and chemically bonded to the supports and that the interactions with the metalized support are stronger. The SP were chromatographically evaluated by the separation of some test mixtures and the performances were similar to those of traditional commercial columns, with column efficiencies higher than 70000 plates m for acenaphthene on the SP without endcapping, and above 56000 plates m with the end-capped SP. The chromatographic characteristics of the SP were similar with regard to hydrophobic, spatial and aromatic selectivities. The end-capped SP presented higher hydrophobicity and lower hydrogen bonding capacity than the not end-capped SP. The metallization procedure increased the acidity of active sites and the ion exchange capacity of zirconized silica. However, the combination of zirconization of the support and the end-capping procedure is an important strategy to obtain SP with high stability. The SP presented potential for the separations of aromatic compounds with different polarities, of pesticides and of pharmaceuticals having basic groups / Doutorado / Quimica Analitica / Doutor em Ciências

A transição do sistema radiográfico convencional para os sistemas radiográficos digitais, ao longo de vinte anos, tem transformado as salas de laudos nos Serviços de Diagnóstico por Imagem tanto na Medicina quanto na Medicina Veterinária. Atualmente, com a introdução do sistema radiográfico computadorizado na rotina de alguns hospitais e laboratório de imagem, o uso das ferramentas do pós-processamento tem se tornado mais freqüente. Diante das vantagens e desvantagens destas ferramentas e da escassez de trabalhos a cerca dos filtros utilizados em imagens radiográficas digitais, o objetivo deste trabalho foi testar o uso dos filtros convencional, realce de borda e invertido, assim como a associação deles na detecção dos padrões pulmonares de cães e gatos. Foram selecionados 40 exames radiográficos do tórax de cães e gatos contendo as três projeções de eleição. Três observadores com diferentes graus de experiência e familiaridade com o sistema radiográfico computadorizado analisaram os filtros individualmente e depois em associação na detecção geral dos padrões pulmanres e individualmente. Obteve-se melhores valores de sensibilidade e especificidade, em geral, quando os observadores experientes utilizaram os três filtros em associação e, para o iniciante, os melhores resultados da sensibilidade e especificidade, em geral, foram no filtro convencional. Os resultados deste trabalho permitiram concluir que houve diferença estatística entre os observadores com distintos graus de experiência e familiaridade com o sistema digital. E que o uso em associação dos filtros pode incrementar o desempenho do radiologista na avaliação radiográfica do parênquima pulmonar. / The transition of the conventional radiographic system to the digital one has been transforming the radiographic routine human and veterinary medicine over the last twenty years. Currently, the introduction of the computed radiography system in some hospitals and imaging services has increased the use of post processing tools. Considering the advantages and disadvantages of these tools and the lack of knowledge about the filters used in digital radiographic images, the aim of this study was to test efficacy of the standard, edge enhancement and gray scale reversed filters and their association to detect pulmonary patterns of cats and dogs. This work selected forty canine and feline sets of thoracic radiographs, including three projections. Three different observers with different degrees of experience and familiarity with the computed radiographic system analyzed the filters individually and then associated in order to detect pulmonary patterns. The best results in sensibility and specificity were related to the more experienced observers using the three associated filters. However, for the beginner, the best sensibility and specificity results was reached with the use of the standard filter in general results. In conclusion were statistical differences between more experienced and familiarized observers with the digital system and the use of filters can increase the radiologist performance when evaluating the pulmonary patterns on the radiography.

Desenvolvemos um modelo na forma de um mapeamento bidimensional simplético (conservativo) para estudar a evolução das linhas de campo magnético de um plasma confinado no interior de um tokamak. Na primeira parte, consideramos dois perfis estudados na literatura para a densidade de corrente no plasma: um monotônico e um não-monotônico, que dão origem a diferentes perfis analíticos do fator de segurança. Nas simulações, consideramos inicialmente o sistema no equilíbrio, onde observamos, nas seções de Poincaré, apenas linhas invariantes. Em seguida, adicionamos uma perturbação (corrente externa), onde observamos cadeias de ilhas e caos no sistema. Na segunda parte consideramos um perfil também não-monotônico, mas com uma região na qual a densidade de corrente no plasma torna-se negativa, estudo ainda em aberto na literatura, que causa uma divergência no perfil do fator de segurança. Mesmo considerando o sistema apenas no equilíbrio, surgiram cadeias de ilhas muito pequenas em torno de curvas sem shear e caos localizado no sistema, característica não verificada para os outros perfis estudados no equilíbrio. Variando parâmetros relacionados à expressão da densidade de corrente, conseguimos controlar o aparecimento de regiões com cadeias de ilhas em torno de curvas sem shear e regiões caóticas. Para comprovar os resultados, aplicamos o perfil considerado a um outro mapa simplético da literatura (tokamap). Na parte final, consideramos a configuração do perfil do fator de segurança na forma de um divertor. Nessa configuração também temos uma divergência na expressão do perfil do fator de segurança. Observamos características similares (cadeias de ilhas em torno de curvas sem shear e caos) quando consideramos o perfil não-monotônico com densidade de corrente reversa. / We develop a symplectic (conservative) bidimensional map to study the evolution of magnetic field lines of a confined plasma in a tokamak. First, we considered two profiles for the plasma current density, studied in the literature: monotonic and non-monotonic, which give rise to different profiles for the poloidal magnetic field and different analytical profiles for the safety factor. In our simulations, we consider the system initially at equilibrium, where we observe, in Poincaré sections, only invariant lines. Then, we add a perturbation (external current), where we observe island chains and chaos in the system. In the second part, we consider a non-monotonic profile, but with a region which the current density becomes negative, which causes a divergence in the safety factor profile. Even considering only the sistem at equilibrium, very small island chains appeared around the shearless curves, and localized chaos. This feature was not observed for the other profiles at equilibrium. We can control the appearance of the regions with island chaind around the shearless curves and chaotic regions, by variation of parameters related to the density current expression. To comprove our results, we aplly the same profile to the other symplectic map. Finally, we consider a safety factor profile in a divertor configuration. We also have a divergence on in the safety factor profile. We observe similar features (island chains around shearless curves and localized chaos) when we consider a non-monotonic safety factor profile with a reversed density current.

Orientador: Isabel Cristina Sales Fontes Jardim / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Química / Made available in DSpace on 2018-08-19T02:08:02Z (GMT). No. of bitstreams: 1 Begnini_FernandaRibeiro_M.pdf: 1951363 bytes, checksum: fe0989f49b67e9b16db7e81f2c1544f5 (MD5) Previous issue date: 2011 / Resumo: Novas fases estacionárias (FE) para Cromatografia Líquida de Alta Eficiência em fase reversa (CLAE-FR) foram preparadas a partir da sorção e imobilização por micro-ondas do copolímero poli(2- fenilpropil)metilsiloxano (PFPMS) sobre suporte de sílica Kromasil (tipo B, esférica, 5 mm). A FE preparada com carga do copolímero de 50%, imobilizada a 540 W por 80 minutos e extraída com clorofórmio (3 horas) e metanol (2 horas) após 8 dias de imobilização, apresentou desempenho cromatográfico satisfatório, com eficiências acima de 60000 pratos/m e parâmetros cromatográficos na faixa aceita pela literatura. Através da caracterização físico-química da FE preparada, pelas técnicas de RMN Si e C, e espectroscopia de absorção no infravermelho, entre outras, foi possível sugerir que o PFPMS encontra-se fisicamente sorvido e quimicamente ligado à sílica. A caracterização cromatográfica mostrou que a FE possui seletividade hidrofóbica, seletividade estérica, pouca interação com analitos polares e grupos silanóis residuais, sendo características apropriadas para uma FR. A FE preparada apresenta grande potencial na separação de agrotóxicos, fármacos e hidrocarbonetos policíclicos aromáticos, além de possuir estabilidade em meio ácido / Abstract: A new stationary phase for reversed-phase high-performance liquid chromatography (RP-HPLC) was prepared by sorption and microwave immobilization of the copolymer poly(2- phenylpropyl)methylsiloxane (PPPMS) onto a silica support (Kromasil®, type B, 5 mm). The stationary phase prepared with copolymeric content of 50%, immobilized at 540 W for 80 min and extracted with chloroform (3 hours) and methanol (2 hours) eight days after immobilization, showed satisfactory chromatographic performance, with efficiency above 60000 plates/m and symmetrical peaks. The physical¿chemical characterization of the new microwave immobilized stationary phase using solid-state NMR spectroscopy and infrared spectroscopy suggested that the copolymer is physically sorbed and chemically bonded onto the silica support. The chromatographic characterization showed that the stationary phase has hydrophobic selectivity, steric selectivity, low interaction with polar analytes and residual silanols, suggesting that the stationary phase prepared is promising to be used in RP-HPLC. The microwave immobilized stationary phase presented chemical stability and potential applicability to separation of pesticides, pharmaceutical drugs and polycyclic aromatic hydrocarbons / Mestrado / Quimica Analitica / Mestre em Química

Technology has become an integral part in the realm of education. The flipped classroom is a recent teaching method where students can watch instructional online videos outside the classroom that actively engage them in their learning process. Although this trend has gained momentum in many disciples and there are many studies available, research behind language acquisition through the flipped classroom model is limited. Still it is implemented by many teachers in the upper secondary school in Sweden. The aim of this study is to investigate the benefits and drawbacks of the flipped classroom in the EFL context and to see if the Flipped Classroom enhances interactive skil ls in students’ language learning. Peer reviewed research articles were used and data has been collected through research behind the Flipped Classroom. The perceptions behind it were divided. Some teachers and students experienced the Flipped Classroom as something positive with regard to availability of material, the promotion of active learning for students and enhancement in language interaction. Along with these, criticism made on this teaching method is that creating material to be available online was time consuming and that perceived an increase in the homework load. As regards oral interaction, both teachers and students felt that it did enhance skills in speaking since preparation before class lead to qualitative time for interaction with the teacher during class, something that was very limited before implementing the flipped classroom model. This review suggests that there is a demand for further studies in the area of English language teaching and English language acquisition in the Swedish context of upper secondary education.

The essay is a manifesto-like personal take on painting, and a redefinition of painting in the digital age. Careless usage of the term ”painting” has led to a diluted descriptive function and a waning categorizing capacity; almost anything can be called painting, which in turn puts actual painting in an awkward position – where it, apart from being itself, could be almost anything. The term “painthing” is introduced to distinguish painting from works that beside its two-dimensional visual information also makes a point of its specific materiality. It brings up cave paintings and links to video-games, suggesting that video-games have gone through the reversed evolution of the history of painting – from abstraction to representation. It speaks of the problems of documentation – the translation of visual information (or re-flattening of a flat surface) – and the cultural equalization of information and images on the internet through the common denominator the pixel. It also describes “information painting”, which in short is digital painting where there is no physical object to be translated to a documentation of itself, but rather a painting that is original in its documentation form (its digital form), painting that strives to be nothing but the utopia of an image – the untouchable/unreachable visual information.

Magister Artium - MA / The objective of the study was to find out whether the decentralisation of responsibulities for social economics development facilitated the management of disaster risk during the 2007 floods in Mozambique. the specific aims of the study were to : analyse and discuss national policies for decentralisation and their significance for DRM. Investigate which responsibilities, human and financial resources were available to local governments for the planning, implemantations and monitoring of DRM activities. Identify mechanisms institutions and activities for DRM and find out whether they provided to be effective. Explore how concerned communities participated in DRM activitiesto reduce their vulnerability to disaster risk.

The tearing mode (TM) is a resistive instability that can arise in magnetically confined plasmas. The TM can be driven unstable by the gradient of the plasma current. When the mode grows it destroys the magnetic field symmetry and reconnects the magnetic field in the form of a so-called magnetic island. The TMs are inherent to a type of device called the reversed-field pinch (RFP), which is a device for toroidal magnetic confinement of fusion plasmas. In the RFP, TMs arise at several resonant surfaces, i.e. where the field lines and the perturbation have the same pitch angle. These surfaces are closely spaced in the RFP and the neighboring TM islands can overlap. Due to the island overlap, the magnetic field lines become tangled resulting in a stochastic magnetic field, i.e. the field lines fill a volume instead of lying on toroidal surfaces. Consequently, a stochastic field results in an anomalously fast transport in the radial direction. Stochastic fields can also arise in other plasmas, for example, the tokamak edge when a resonant magnetic perturbation (RMP) is applied by external coils. This stochastization is intentional to mitigate the edge-localized modes. The RMPs are also used for control of other instabilities. Due to the finite number of RMP coils, however, the RMP fields can contain sidebands that decelerate and lock the TMs via electromagnetic torques. The locking causes an increased plasma-wall interaction. And in the tokamak, the TM locking can cause a plasma disruption which is disastrous for future high-energy devices like the ITER. In this thesis, the TM locking was studied in two RFPs (EXTRAP T2R and Madison Symmetric Torus) by applying RMPs. The experiments were compared with modern mode-locking theory. To determine the viscosity in different magnetic configurations where the field is stochastic, we perturbed the momentum via an RMP and an insertable biased electrode. In the TM locking experiments, we found qualitative agreement with the mode-locking theory. In the model, the kinematic viscosity was chosen to match the experimental locking instant. The model then predicts the braking curve, the short timescale dynamics, and the mode unlocking. To unlock a mode, the RMP amplitude had to decrease by a factor ten from the locking amplitude. These results show that mode-locking theory, including the relevant electromagnetic torques and the viscous plasma response, can explain the experimental features. The model required viscosity agreed with another independent estimation of the viscosity. This showed that the RMP technique can be utilized for estimations of the viscosity. In the momentum perturbation experiments, it was found that the viscosity increased 100-fold when the magnetic fluctuation amplitude increased 10-fold. Thus, the experimental viscosity exhibits the same scaling as predicted by transport in a stochastic magnetic field. The magnitude of the viscosity agreed with a model that assumes that transport occurs at the sound speed -- the first detailed test of this model. The result can, for example, lead to a clearer comparison between experiment and visco-resistive magnetohydrodynamics (MHD) modeling of plasmas with a stochastic magnetic field. These comparisons had been complicated due to the large uncertainty in the experimental viscosity. Now, the viscosity can be better constrained, improving the predictive capability of fusion science. / <p>QC 20171122</p>