Made available in DSpace on 2018-08-01T21:58:49Z (GMT). No. of bitstreams: 1 tese_10834_DISSERTAÇÃO - FINAL_Ivan.pdf: 3037729 bytes, checksum: 68211b54960caf2a6fb162c0f66c89c7 (MD5) Previous issue date: 2017-04-11 / No presente trabalho avaliou-se a influência dos contraíons de sais Cu2+ (acetato e cloreto) e as condições de síntese (temperatura, tempo e concentração) sobre o rendimento da reação do MOF-199, uma rede metalorgânica bem conhecida. Para tanto, foi realizado um planejamento fatorial com três parâmetros de síntese: temperatura, tempo e concentração de Cu2+, variando em dois níveis (mínimo e máximo), resultando em uma análise combinatória, em que cada experimento consistiu em uma configuração diferente dos fatores em seus respectivos níveis, o que levou a uma batelada de 23 = 8 experiências, para cada contraíon. Foram também realizadas sínteses com valores médios de cada parâmetro de reação, totalizando 9 sínteses para cada contraíon. O rendimento do produto da reação foi a variável resposta do planejamento fatorial. Os produtos foram caracterizados por espectroscopia de absorção vibracional na região do infravermelho, análise termogravimétrica e difração de raios X de pó. As técnicas analíticas confirmaram a obtenção de MOF-199. A temperatura nas sínteses com cloreto de Cu2+ foi a única variável significativa nos rendimentos de reação. As sínteses realizadas com acetato de Cu2+ proporcionaram rendimentos mais elevados em comparação ao cloreto de Cu2+, embora as condições de síntese não tenham sido significativas.

Asphalt’s fatigue and modulus characteristics play an important role in pavement design. Ultimately they govern the required thickness of asphalt to structurally support heavy vehicles. The thickness of the asphalt layer is a major contributor to the cost of construction. In New Zealand, the design of structural asphalt layers has been a problem for some time and gives rise to two areas of concern. First, the present fatigue failure criterion, the Shell fatigue transfer function, which has been adopted from overseas, not only underestimates the fatigue life of the country’s asphalts, but does not accurately characterise the fatigue behaviour of our local asphalt mixes. Consequently, asphalt thicknesses are overdesigned. Second, asphalt’s fatigue behaviour is influenced by numerous factors and therefore can be difficult to characterise. The primary objective of this thesis is to develop fatigue and modulus models, by carrying out fatigue and modulus tests, to characterise the behaviour of two typical New Zealand structural asphalts. Both resilient and stiffness moduli tests were performed at a range of temperatures and loading rates developing moduli master curves, which predict the asphalt’s modulus for any pavement temperature and vehicle speed. A general full factorial experiment was carried out utilising the four-point flexural beam fatigue test. Tests were carried out at different strain levels, temperatures, and loading rates. An analysis of variance showed that the impacts of strain amplitude, temperature, binder type, the interaction of strain amplitude and temperature, and the interaction of strain amplitude and binder type have a significant effect on fatigue behaviour. The developed models, which account for temperature effects give the pavement engineer the ability to undergo a more accurate assessment of fatigue damage than at present for different climatic temperatures demonstrated by using an incremental damage analysis approach. The research shows that with such characterisation for the given pavement’s design life, thinner and less expensive roads can be constructed in New Zealand.

A hidrofobicidade e a estrutura planar do orbital π estendido de fotossensibilizadores do tipo clorina e hipericina podem favorecer a agregação destes compostos em meio aquoso. Esta agregação pode reduzir a eficiência fotodinâmica e a aplicabilidade destes compostos em diagnósticos e na Terapia fotodinâmica. Uma estratégia para minimizar esta limitação é a modificação destas moléculas pela inserção de grupos hidrofílicos. Neste trabalho foram utilizadas técnicas espectroscópicas para caracterizar as propriedades físico-químicas e fotodinâmicas de derivados de clorina (CHL), e hipericina (HY) obtidos por meio de inserções dos grupos hidrofílicos trizma e glucamina, respectivamente: Clorina-Trizma (CHL-T) e Hipericina Glucamina (HY-G). Os resultados mostraram que estas modificações estruturais aumentaram em até 20% a solubilidade destes compostos em meio aquoso. No entanto, devido à solubilidade parcial dos fotossensibilizadores na ausência de cargas elétricas foram identificados agregados do tipo H em meio ácido, neutro e na presença de íons em solução aquosa. Tais agregados foram solubilizados em meio alcalino e por microambientes micelares dos surfactantes CTAB, SDS e Tween 20. Os agregados do tipo H acarretaram ainda na redução da constante de velocidade de fotobranqueamento e da formação de oxigênio singleto dos fotossensibilizadores em meio aquoso. Contudo, as clorinas foram cerca de 15 vezes mais eficientes do que a hipericinas na geração deste radical citotóxico. A análise sistemática do potencial fotodinâmico dos fotossensibilizadores em células VERO e HUVEC (não tumorais) e HEp-2 (tumoral) foi realizada por meio de um planejamento fatorial combinando-se a concentração, tempo de acumulação do fotossensibilizador no interior da célula e a dose de luz. Esta análise mostrou que o tempo de acumulação do fotossensibilizador é um parâmetro significante para se erradicar seletivamente as células cancerígenas. Ao contrário das células não tumorais, nas células HEp-2 a quantidade de fotossensibilizador acumulado foi proporcional à lipoficilidade dos fotossensibilizadores. A análise quimiométrica resultou ainda em um modelo matemático para a estimativa dos valores da concentração inibitória média que foi validada por meio de comparação estatística com os valores experimentais determinados para os fotossensibilizadores. As hipericinas foram mais fototóxicas para as células tumorais do que as clorinas. Nas células não tumorais os derivados foram menos citotóxicos, sugerindo o uso destes compostos para a inativação seletiva de células tumorais. Todas essas características permitem que os compostos sejam empregados como fotossensibilizadores em diagnósticos e tratamentos fotodinâmicos. / The hydrophobicity and planar structure of π extended orbital of photosensitizers like chlorine and hypericin may favor the aggregation of these compounds in aqueous medium. This aggregation can reduce their photodynamic efficiency and applicability in Photodynamic Therapy and diagnosis. A strategy to minimize this limitation is the modification of these molecules by the inclusion of hydrophilic groups. In this study spectroscopic techniques were used to characterize the physical-chemistry and photodynamic properties of chlorin (CHL) and hypericin (HY) derivatives obtained by insertion of trizma glucamine and hydrophilic groups, respectively: Trizma-Chlorin (CHL-T) and glucamine Hypericin (HY-G). The results showed that these structural modifications increased by 20% the solubility of these compounds in an aqueous medium. However, due to partial solubility of the photosensitizers in electric charges absence, H-aggregates were found in acid, neutral and ions presence in aqueous solution. These aggregates were solubilized by alkaline medium and micelar microenvironments of CTAB, SDS and Tween 20. H-aggregates were also responsible for the minor photobleaching rate constant and singlet oxygen formation by photosensitizers in an aqueous medium. Although, chlorins were about 15 times more efficient than hypericins on the singlet oxygen generation. The systematic analysis of photosensitizers photodynamic potential in Vero and HUVEC (non-tumor cells) and HEp-2 (tumor cells) was done using a factorial design combining the concentration of the photosensitizer, accumulation time of it into the cell and light doses. This analysis showed that the photosensitizer accumulation time is a significant parameter to eradicate selectively tumor cells. In contrast to non-tumor cells, in HEp-2 cells the accumulation rate was proportional of the lipophylicity of photosensitizer. The chemometric analysis resulted also in a mathematical model to estimate the half inhibitory concentration values. It had been statistical validated by comparing the experimental values determined for the photosensitizers. The hypericins have been more phototoxic to tumor cells than chlorines. In non-tumor cells derivatives were more cytotoxic than original compounds suggesting the use of these compounds for the selective inactivation of tumor cells. All these characteristics allow the use of these compounds as photosensitizers in photodynamic diagnostics and treatments.

A hidrofobicidade e a estrutura planar do orbital π estendido de fotossensibilizadores do tipo clorina e hipericina podem favorecer a agregação destes compostos em meio aquoso. Esta agregação pode reduzir a eficiência fotodinâmica e a aplicabilidade destes compostos em diagnósticos e na Terapia fotodinâmica. Uma estratégia para minimizar esta limitação é a modificação destas moléculas pela inserção de grupos hidrofílicos. Neste trabalho foram utilizadas técnicas espectroscópicas para caracterizar as propriedades físico-químicas e fotodinâmicas de derivados de clorina (CHL), e hipericina (HY) obtidos por meio de inserções dos grupos hidrofílicos trizma e glucamina, respectivamente: Clorina-Trizma (CHL-T) e Hipericina Glucamina (HY-G). Os resultados mostraram que estas modificações estruturais aumentaram em até 20% a solubilidade destes compostos em meio aquoso. No entanto, devido à solubilidade parcial dos fotossensibilizadores na ausência de cargas elétricas foram identificados agregados do tipo H em meio ácido, neutro e na presença de íons em solução aquosa. Tais agregados foram solubilizados em meio alcalino e por microambientes micelares dos surfactantes CTAB, SDS e Tween 20. Os agregados do tipo H acarretaram ainda na redução da constante de velocidade de fotobranqueamento e da formação de oxigênio singleto dos fotossensibilizadores em meio aquoso. Contudo, as clorinas foram cerca de 15 vezes mais eficientes do que a hipericinas na geração deste radical citotóxico. A análise sistemática do potencial fotodinâmico dos fotossensibilizadores em células VERO e HUVEC (não tumorais) e HEp-2 (tumoral) foi realizada por meio de um planejamento fatorial combinando-se a concentração, tempo de acumulação do fotossensibilizador no interior da célula e a dose de luz. Esta análise mostrou que o tempo de acumulação do fotossensibilizador é um parâmetro significante para se erradicar seletivamente as células cancerígenas. Ao contrário das células não tumorais, nas células HEp-2 a quantidade de fotossensibilizador acumulado foi proporcional à lipoficilidade dos fotossensibilizadores. A análise quimiométrica resultou ainda em um modelo matemático para a estimativa dos valores da concentração inibitória média que foi validada por meio de comparação estatística com os valores experimentais determinados para os fotossensibilizadores. As hipericinas foram mais fototóxicas para as células tumorais do que as clorinas. Nas células não tumorais os derivados foram menos citotóxicos, sugerindo o uso destes compostos para a inativação seletiva de células tumorais. Todas essas características permitem que os compostos sejam empregados como fotossensibilizadores em diagnósticos e tratamentos fotodinâmicos. / The hydrophobicity and planar structure of π extended orbital of photosensitizers like chlorine and hypericin may favor the aggregation of these compounds in aqueous medium. This aggregation can reduce their photodynamic efficiency and applicability in Photodynamic Therapy and diagnosis. A strategy to minimize this limitation is the modification of these molecules by the inclusion of hydrophilic groups. In this study spectroscopic techniques were used to characterize the physical-chemistry and photodynamic properties of chlorin (CHL) and hypericin (HY) derivatives obtained by insertion of trizma glucamine and hydrophilic groups, respectively: Trizma-Chlorin (CHL-T) and glucamine Hypericin (HY-G). The results showed that these structural modifications increased by 20% the solubility of these compounds in an aqueous medium. However, due to partial solubility of the photosensitizers in electric charges absence, H-aggregates were found in acid, neutral and ions presence in aqueous solution. These aggregates were solubilized by alkaline medium and micelar microenvironments of CTAB, SDS and Tween 20. H-aggregates were also responsible for the minor photobleaching rate constant and singlet oxygen formation by photosensitizers in an aqueous medium. Although, chlorins were about 15 times more efficient than hypericins on the singlet oxygen generation. The systematic analysis of photosensitizers photodynamic potential in Vero and HUVEC (non-tumor cells) and HEp-2 (tumor cells) was done using a factorial design combining the concentration of the photosensitizer, accumulation time of it into the cell and light doses. This analysis showed that the photosensitizer accumulation time is a significant parameter to eradicate selectively tumor cells. In contrast to non-tumor cells, in HEp-2 cells the accumulation rate was proportional of the lipophylicity of photosensitizer. The chemometric analysis resulted also in a mathematical model to estimate the half inhibitory concentration values. It had been statistical validated by comparing the experimental values determined for the photosensitizers. The hypericins have been more phototoxic to tumor cells than chlorines. In non-tumor cells derivatives were more cytotoxic than original compounds suggesting the use of these compounds for the selective inactivation of tumor cells. All these characteristics allow the use of these compounds as photosensitizers in photodynamic diagnostics and treatments.

Made available in DSpace on 2017-07-10T13:59:25Z (GMT). No. of bitstreams: 1 DEFESA_SARAH_M_MARTINS.pdf: 1948811 bytes, checksum: b506b11e5b86370135e564286deabd70 (MD5) Previous issue date: 2015-11-24 / In recent years, the interest of the pharmaceutical industry for new drugs delivery system has been growing, especially aiming the optimization of therapy and reduction of side effects caused by conventional treatments. The multiparticulate systems, besides their techonological and biopharmaceutical advantages when compared to the monolithic systems, allow obtaining different ways of drug delivery, such as the biphasic system, capable of delivering the drug in separate fractions into the bloodstream, and ideal for the treatment of circadian diseases. Thus, this study aimed to obtain a multi particulate system biphasic release, lasting 24 hours, using a combination of polymeric materials hydroxypropyl methylcellulose and ethyl cellulose, as well as a full factorial design 2² to optimize the development stage. Furthermore, it was developed and validated analytical method by UV spectroscopy able to quantify the model drug used, propranolol hydrochloride (PROP) test and the content of dissolution of the dosage form. Using the sugar spheres coating technology, it was possible to obtain the proposed system with a reduced number of experiments. Pellets produced and used in the biphasic formulations showed mechanical characteristics within the expected quality parameters, showing that the technique is robust and can be applied on an industrial scale. The analytical method for the quantification of the proposed drug was linear, precise, accurate, robust against variations in wavelength of mark and sonication solvent in a concentration range of 0.80 - 96 mg L-1 and stable the experimental conditions analyzed, showing a method capable of generating highly reliable results and therefore able to be used in the laboratory routine quality control. / Nos últimos anos, o interesse da indústria farmacêutica por novos sistemas de liberação de fármacos vem crescendo, visando sobretudo a otimização da terapêutica e a diminuição dos efeitos colaterais ocasionados pelos tratamentos convencionais. Os sistemas multiparticulados, além de possuírem vantagens tecnológicas e biofarmacêuticas quando comparadas aos sistemas monolíticos, possibilitam a obtenção de diferentes padrões de liberação de drogas, como por exemplo, o sistema bifásico, capaz de disponibilizar o fármaco em frações distintas para a corrente sanguínea, sendo ideais para o tratamento das doenças circadianas. Desta maneira, o presente trabalho teve como objetivo a obtenção de um sistema multiparticulado de liberação bifásica, com duração de 24 horas, utilizando a combinação dos materiais poliméricos hidroxipropilmetilcelulose e etilcelulose, bem como um planejamento fatorial completo 2² para a otimização da etapa de desenvolvimento. Além disso, foi desenvolvido e validado um método analítico por espectroscopia de UV capaz de quantificar o fármaco modelo utilizado, cloridrato de propranolol (PROP), nos ensaios de teor e dissolução desta forma farmacêutica. Utilizando-se a tecnologia de revestimento de núcleos inertes de sacarose, foi possível a obtenção do sistema proposto com um número reduzido de experimentos. Os péletes produzidos e utilizados nas formulações bifásicas apresentaram características mecânicas dentro dos parâmetros de qualidade esperados, demostrando que a técnica é robusta e pode ser aplicada em escala industrial. O método analítico proposto para a quantificação do fármaco, mostrou-se linear, preciso, exato, robusto em relação a variações no comprimento de onda, marca de solvente e sonicação na faixa de concentração de 0,80 96 μg mL-1 e estável nas condições experimentais analisadas, evidenciando um método capaz de gerar resultados de alta confiabilidade e portanto apto a ser utilizado na rotina laboratorial de controle de qualidade.

In this project, two broad facets in the design of a methodology for performance optimization of indexable carbide inserts were examined. They were physical destructive testing and software simulation.For the physical testing, statistical research techniques were used for the design of the methodology. A five step method which began with Problem definition, through System identification, Statistical model formation, Data collection and Statistical analyses and results was indepthly elaborated upon. Set-up and execution of an experiment with a compression machine together with roadblocks and possible solution to curb road blocks to quality data collection were examined. 2k factorial design was illustrated and recommended for process improvement. Instances of first-order and second-order response surface analyses were encountered. In the case of curvature, test for curvature significance with center point analysis was recommended. Process optimization with method of steepest ascent and central composite design or process robustness studies of response surface analyses were also recommended.For the simulation test, AdvantEdge program was identified as the most used software for tool development. Challenges to the efficient application of this software were identified and possible solutions proposed. In conclusion, software simulation and physical testing were recommended to meet the objective of the project.

Abstract SMT process is the most critical process to influence products quality in electronic assembly house process. Especially,the solder paste printing control is the key process to determine the yield rate of SMT quality. To own the capability to control quality of solder paste printing is the important thing what assembly house have to face it¡C For the purpose of gaining good SMT yield & solder paste printing stability ,the study use six sigma management technique & procedure (DMAIC--Define¡BMeasure¡BAnalyze¡BImprove & Control) make the main factors of solder paste printing¡Aincluding Printing speed¡BScraper pressure¡BStencil clean frequency¡Ato be the experiment factors of DOE(Design of Experiment)¡CThe DOE minimize the experiment number of times and provide a way of 2 levels factorial design combine RSM(Response Surface Methodology) experiment to get the optimization combination of factors¡¦ levels. Then evaluate how the optimization combination of factor levels to influence the quality of SMT¡C The study final found that there are a surprised & satisfied result on SMT yield improvement caused by optimization combination of factors¡¦ levels which 2 levels factorial design combine RSM experiment generated. It can provide the procedure & methodology for SMT assembly house reference to improve yield rate .

Background: Electronic prescribing systems are designed to aid in the complex process of prescribing by providing patient information and decision support at the point of care. Successful implementation and effectiveness depend on a variety of factors, including usability and user interface design, which influence how the information and decision support are relayed to users. Poorly designed systems have been found to be associated with medication errors. Methods: We conducted a factorial design study to investigate the impact of screen density, highlighting, and placement of information, on the accuracy of prescribing when using an e-prescribing system. Study sessions were held during clinical pharmacology educational rounds, where residents and medical students answered simulated prescribing scenarios presented on various e-prescribing system interface configurations. Assignment of prescribing scenarios to interface configurations and presentation order were randomized between study sessions. Participants were also asked about their preferences for specific user interface configurations. Results: A total of 66 participants completed 844 prescribing cases, with 583 (69%) cases answered correctly. The presence of highlighting was associated with correct prescribing decisions (p-value = 0.001), with 181 out of 250 (72.4%) prescribing scenarios answered correctly on interfaces with highlighting of key clinical information, as opposed to 156 out of 242 (64.5%) on interface configurations without. Low screen density and central placement of information were not found to be statistically significant predictors of prescribing accuracy. The presence of highlighting was the only factor that the majority of participants (80.3%) preferred, but no effect was found when comparing prescribing accuracy on preferred versus non-preferred interface configurations. Conclusions: The factorial design methodology developed is a novel approach for efficient and objective evaluation of multiple user interface design factors in one study. Evidence-based design and usability principles are needed to enhance the design and appropriate use of e-prescribing systems as usability problems continue to be one of the primary reasons for dissatisfaction and poor levels of adoption. / Thesis / Master of Science (MSc)

The thesis focuses on the development of statistical theory in experimental design with applications in global optimization. It consists of four parts. In the first part, a criterion of design efficiency, under model uncertainty, is studied with reference to possibly nonregular fractions of general factorials. The results are followed by a numerical study and the findings are compared with those based on other design criteria. In the second part, optimal designs are dentified using Bayesian methods. This work is linked with response surface methodology where the first step is to perform factor screening, followed by response surface exploration using different experiment plans. A Bayesian analysis approach is used that aims to achieve both goals using one experiment design. In addition we use a Bayesian design criterion, based on the priors for the analysis approach. This creates an integrated design and analysis framework. To distinguish between competing models, the HD criterion is used, which is based on the pairwise Hellinger distance between predictive densities. Mixed-level fractional factorial designs are commonly used in practice but its aliasing relations have not been studied in full rigor. These designs take the form of a product array. Aliasing patterns of mixed level factorial designs are discussed in the third part. In the fourth part, design of experiment ideas are used to introduce a new global optimization technique called SELC (Sequential Elimination of Level Combinations), which is motivated by genetic algorithms but finds the optimum faster. The two key features of the SELC algorithm, namely, forbidden array and weighted mutation, enhance the performance of the search procedure. Illustration is given with the optimization of three functions, one of which is from Shekel's family. A real example on compound optimization is also given.

Ti-6Al-4V has a wide range of applications such as in the automotive and aerospace industries. Nevertheless, titanium alloys are very difficult to machine by conventional methods. Micro-EDM is a non-conventional machining method that uses the thermal effect of precisely controlled sparks. Manufacturers are looking for the methods and optimal settings to increase the productivity of micro-EDM in terms of lessening machining time and tool wear. Moreover, surface integrity of the machined area is crucial for some products such as biomedical implants. The objective of this study was to investigate the effects of the micro-EDM process parameters on response variables, in order to understand the behavior of each parameter as well as to determine their optimal values. Although, there is a substantial amount of literature studying different aspects of micro-EDM, most of them were designed based on the one-factor-at-a-time experiments instead of studying all factors, simultaneously. This research was conducted through a series of experiments using a full factorial design. An analysis of variance was employed to analyze the findings and to determine the effect and significance of each process parameters on the response variables. The process parameters included voltage, capacitance, electrode rotational speed, and electrode coating. Voltage and capacitance were studied separately as well as in combination in terms of the discharge energy. Response variables consisted of machining time, tool wear, crater size, microhardness, and element characterization. The surface morphology and element characterization were studied through the application of SEM and EDS analysis. The findings indicated that voltage had a decreasing effect on machining time, while it increased the crater size. Capacitance decreased machining time and tool wear. It had an increasing effect on the surface hardness. The effects of the TN-coating and electrode rotational speed were not statistically significant. Voltage and capacitance were the only parameters affecting element characterization. The affected elements included Ti, Al, C, and W. The optimal process parameters for two sets of response variables were determined using Minitab 17.