The successful clinical translation of non-viral gene delivery systems has yet to be achieved due to the biological and technical obstacles to preparing a safe, potent and cost-effective vector. Hyperbranched polymers have emerged as promising candidates to address gene delivery barriers owing to their relatively simple synthesis and ease of modification compared to other polymers, which makes them more feasible for scale up and manufacturing. In the first part of this thesis, we compare hyperbranched poly(amino acids) synthesised by co-polymerising histidine and lysine, with hyperbranched polylysine prepared using the well-known 'ultra-facile' thermal polycondensation route, to investigate the effects of histidine units on the structure and gene delivery applications of the resultant materials. The conditions of polymerisation were optimised to afford water-soluble hyperbranched polylysine-co-histidine of three different molar ratios with molecular masses varying from 13-30 kDa. Spectroscopic, rheological and thermal analysis indicated that the incorporation of histidine modulated the structure of hyperbranched polylysine to produce a more dendritic polymer with less flexible branches. Experiments to probe gene delivery to A549 and H1299 cells, surprisingly, indicated that the co-polymers containing histidine were not more effective in transfecting a luciferase gene than hyperbranched polylysines synthesised as established literature comparators. We attribute the variations in gene delivery efficacy to the changes induced in polymer architecture by the branching points at histidine residues, and obtain structure-function information relating histidine content with polymer Tg, pKa and ability to form stable polyplexes with plasmid DNA. These results are of significance to nanomedicine design as they indicate that addition of histidine as a co-monomer in the synthetic route to hyperbranched polymers changes not only the buffering capacity of the polymer but has significant effects on the overall structure, architecture and gene delivery efficacy. It has become known that many cationic polymers are cytotoxic and although a large number of polycations have now designed to address the toxicity problem, there is still a practical need to develop a fast and reliable method for assessing the safety of these materials. In this regard, metabolomics provides a high throughput and comprehensive method that can assess the potential toxicity at the cellular and molecular level. Therefore, in the second part of this thesis, metabolomics was applied to investigate the impact of hyperbranched polylysine, hyperbranched polylysine-co-histidine and branched polyethylenimine polyplexes, on the metabolic pathways of A459 and H1299 cell lines. The study revealed that the polyplexes downregulated metabolites associated with glycolysis and the TCA cycle, and induced oxidative stress in both cell lines. The fold changes of the metabolites indicated that the polyplexes of polyethylenimine and hyperbranched polylysine affected the metabolism much more than the polyplexes of hyperbranched polylysine-co-histidine. This was in line with transfection results, suggesting a correlation between the toxicity and transfection efficiency of these polyplexes. This part highlights the importance of metabolomics approaches not just to assess the potential toxicity of polyplexes but also to understand the molecular mechanisms underlying their action, which could help to design more efficient vectors. In the third part of this thesis, we investigated the ability of the hyperbranched polymers to condense and deliver siRNA. The results indicated that the higher molecular mass polymers achieved better siRNA delivery and gene silencing than the lower molecular mass form of the polymers and the lysine-only polymer was more efficient than the histidinylated one. These results can be attributed to the low charge (molecular mass) and stiffness of siRNA molecules in comparison with plasmid DNA, which in combination with the impact of histidine incorporation on the structure of the hyperbranched polymers can also explain the lower efficiency of histidinylated polymers. Overall, this thesis is highlighted the impacts of structural factors on the gene delivery applications of hyperbranched polymers and the importance of these factors to inform the design of new polymeric vectors. Also, metabolomics approaches were introduced to this area, not only to evaluate the safety of gene vectors but also to understand the molecular basis by which these vectors act. The data together suggest that the hyperbranched polymers prepared during thermal polycondensation of amino acids have some efficacy in preliminary gene delivery applications, and that these might be improved with future studies to be a candidate for clinical purposes.

O Lean Six Sigma é a metodologia originada a partir da integração das metodologias Lean e Six Sigma. O Lean Six Sigma procura eliminar as perdas e reduzir os defeitos, agregando os benefícios de cada uma das duas metodologias que a dão origem. O objetivo deste trabalho é aplicar a metodologia Lean Six Sigma para melhoria de um processo produtivo. Neste trabalho é apresentada uma revisão bibliográfica sobre as metodologias Lean e Six Sigma, buscando a compreensão das origens do Lean Six Sigma, e uma revisão sobre a metodologia Lean Six Sigma. Baseado na revisão bibliográfica é apresentada uma metodologia para aplicação do Lean Six Sigma, que tem por estrutura o DMAIC (Define, Measure, Analyze, Improve and Control). Na sequência esta metodologia é aplicada para melhoria de um processo produtivo. Os resultados da aplicação do Lean Six Sigma foram: aumento do nível de sigma e redução dos defeitos do processo, demonstrando que as metodologias Lean e Seis Sigma podem ser integradas, e como ocorre essa integração. Os fatores de sucesso da aplicação da metodologia Lean Six Sigma também foram evidenciados. / Lean Six Sigma is a methodology originated from the integration of Lean and Six Sigma. Lean Six Sigma seeks for eliminate waste and reduce defects, combining benefits from both methodologies. The objective of this dissertation is apply the Lean Six Sigma methodology to improve a production process. In this dissertation is presented a bibliography review about the Lean and Six Sigma methodology, looking for understanding of the Lean Six Sigma sources and a review about the Lean Six Sigma methodology. Based on the bibliography review is presented a methodology to apply Lean Six Sigma, that has the DMAIC as the structure (Define, Measure, Analyze, Improve and Control). This methodology is applied to improve a production process. The results of the Lean Six Sigma application were the increase of sigma level and reduction of process defects, showing that Lean and Six Sigma can be combined and how this combination happens. The success factors of the application of Lean Six Sigma methodology were evidenced.

Copy of author's previously published article inserted. Bibliography: leaves 180-195. Investigation of the contribution of polyphenol oxidase (PPO) and peroxidase (POD) to enzymic browning in sugarcane juice.

Because of limited tester time and memory, a primary goal of digital circuit manufacture test generation is to create compact test sets. Test generation programs that use Ordered Binary Decision Diagrams (OBDDs) as their primary functional representation excel at this task. Unfortunately, the use of OBDDs limits the application of these test generation programs to small circuits. This is because the size of the OBDD used to represent a function can be exponential in the number of the function's switching variables. Working with these functions can cause OBDD-based programs to exceed acceptable time and memory limits. This research proposes using Ordered Partial Decision Diagrams (OPDDs) instead as the primary functional representation for test generation systems. By limiting the number of vertices allowed in a single OPDD, complex functions can be partially represented in order to save time and memory. An OPDD-based test generation system is developed and techniques which improve its performance are evaluated on a small benchmark circuit. The new system is then demonstrated on larger and more complex circuits than its OBDD-based counterpart allows.

Additive Manufacture (AM) is a novel manufacturing method; it is a process of forming components by adding materials. Owing to material saving and manufacturing cost saving, more and more research has been focused on metal AM technologies. WAAM is one AM technology, using arc as the heat sources and wire as the material to create parts with weld beads on a layer-by-layer basis. The process can produce components in a wide range of materials, including aluminum, titanium and steel. High deposition rate, material saving and elimination of tooling cost are critical characteristics of the process. Cost estimation is important for all companies. The estimated results can be used as a datum to create a quote for customers or evaluate a quote from suppliers, an important consideration for the application of WAAM is its cost effectiveness compared with traditional manufacture methods. The aim of this research is to find a way to develop a cost estimating method capable of providing manufacturing cost comparison of WAAM with CNC. A cost estimation model for CNC machining has been developed. A process planning approach for WAAM was also defined as part of this research. An Excel calculation spreadsheet was also built and it can be easily used to estimate and compare manufacture cost of WAAM with CNC. Using the method developed in this research, the cost driver analysis of WAAM has been made. The result shows that reduced material cost is the biggest cost driver in WAAM. The cost comparison of WAAM and CNC also has been made and the results show that with the increase of buy-to-fly ratio WAAM is more economical than CNC machining.

Nanotechnology enabled synthesis of various shapes and morphologies of conventional materials. Nanotubes, nanoparticles, quantum dots and nanowires are the new form of materials. Especially nanowires have gotten great attention due to their unique physical, chemical and optical properties. Superior properties of nanowires are based on their high surface area and two quantum confinement directions. Silver is one of the most conductive metals and it has the highest thermal conductivity. Due to excellent properties of bulk silver its nanostructures especially silver nanowires have been widely studied. Silver nanowires have been demonstrated to be used in optical polarizers, photonic crystals, surface enhanced Raman spectroscopy and recently transparent and conducting electodes. Hence, production of silver nanowires through a cost-effective and well controlled method could make important contributions to these and other unprecedented. So far, many different methods have been explored for the synthesis of silver nanowires. Vapor-liquid-solid (VLS) technique, hard template techniques such as porous anodic alumina synthesis and soft template techniques such as DNA based synthesis and polyol process are some silver nanowire synthesis methods. Among these methods, solution based polyol process is the most feasible one in terms of cost, yield and simplicity. In this thesis, polyol process, which is a novel and solution based method enabling the synthesis of silver nanowires with precise length and diameter control, is investigated. A detailed parametric study resulting in a full control over the resultant nanowire morphology is provided. The parameters affecting the structure have been determined as temperature, injection rate, poly(vinylpyrrolidone):silver nitrate (PVP:AgNO3) molar ratio, sodium chloride (NaCl) amount and stirring rate. The results show that polyol process method could replace the conventional silver nanowire fabrication methods. It was shown that specific nanowire lengths and diameters for any application can be obtained simply by adjusting the parameters of the process.

Because of limited tester time and memory, a primary goal of digital circuit manufacture test generation is to create compact test sets. Test generation programs that use Ordered Binary Decision Diagrams (OBDDs) as their primary functional representation excel at this task. Unfortunately, the use of OBDDs limits the application of these test generation programs to small circuits. This is because the size of the OBDD used to represent a function can be exponential in the number of the function's switching variables. Working with these functions can cause OBDD-based programs to exceed acceptable time and memory limits. This research proposes using Ordered Partial Decision Diagrams (OPDDs) instead as the primary functional representation for test generation systems. By limiting the number of vertices allowed in a single OPDD, complex functions can be partially represented in order to save time and memory. An OPDD-based test generation system is developed and techniques which improve its performance are evaluated on a small benchmark circuit. The new system is then demonstrated on larger and more complex circuits than its OBDD-based counterpart allows.

Thesis (doctoral)--Helsinki University of Technology, 2000. / Includes bibliographical references. Also available on the World Wide Web.

Thesis--Columbia University, 1931. / Vita. Published also as Studies in history, economics and public law, no. 342. "The third volume to appear as a result of studies in th field of Negro migration under grants by the Social Science Research Council and the Columbia University Council for Research in the Social Sciences."--Foreword. "Selected bibliography": p. 134-135.

An advancement of the two stage growth recipe for the fabrication of CIGS solar cells was developed. The developed advancement was inconsistent in producing samples of similar stoichiometry. This was a huge barrier for up scaling the process as the behavior of devices would be different due to variation in stoichiometry. Samples with reproducible stoichiometry were obtained once the heating rate of elements, selenium in particular was better understood. This is mainly attributed to the exponential increase of selenium flux after its evaporation temperature. Monitoring the selenium flux was vital in getting constant selenium fluxes. Few changes to the growth recipe were induced to optimize the amount of selenium being used. Depositions were done using constant selenium to metal flux ratio of 5. Elemental tradeoffs were observed as a result of the growth recipe change. These tradeoffs are in favor of the two stage growth recipe. The solar cells were fabricated on a soda lime glass substrate with a molybdenum back contact. Improper sample cleaning and storage were found to affect the deposition outcome of the molybdenum back contact. This also had a cascading effect on the absorber layer. Residual precipitates during deposition of CdS were avoided by increasing the spinner speed which increased the reaction rate. This is attributed to the growth of CdS either by cluster-by-cluster growth or by ion-by-ion growth. SEM, EDS were some important tools used to characterize the devices. EDS in particular, was used extensively at different stages throughout the growth process to ensure that we were heading in the right direction. Current-voltage (I-V) measurements were done to study the solar cell performance under light and dark.