The high functionality epoxy resins tetraglycidyl-4,4’-diaminodiphenyl-methane(TGDDM) and triglycidyl-p-aminophenol (TGPAP) are the main components in most aerospace grade epoxy resin formulations. Owing to their high reactivity and high viscosity, TGDDM and TGPAP pose difficulties when used in wet layup composite manufacturing. As such, these resins are often modified to achieve the desired performance both in the liquid and cured states. The main objective of this thesis is to optimise a low viscosity multi-component epoxy resin formulation suitable for use as an aerospace grade composite matrix. The formulation will allow for the addition of high levels of thermoplastic to improve the fracture toughness of the resin whilst also maintaining resin processability. Through the use of thermal analytical techniques this thesis aims to study the effects of varying the TGDDM/TGPAP ratio, incorporation of a low viscosity bi-functional epoxy resin, the diglycidyl ether of bisphenol F (DGEBF) and changes to the stoichiometric ratio (r)between reactive groups of the epoxy resin and amine hardener (4,4’-diaminodiphenylsulphone, DDS) in multi-component epoxy resin formulations. Resin formulations were optimised using factorial experimental design (FED). Results from two FED’s showed curing multi-component resins at a low stoichiometric ratio significantly increased the processing window whilst also increasing the glass transition temperature (Tg) of the cured resin. No apparent benefit could be assigned to the inclusion of TGDDM owing to its poor processability and a Tg similar to TGPAP. Up to 60% DGEBF was incorporated in a multi-component resin formulation whilst still attaining a Tg greater than 220°C. Its inclusion at 60% had the additional benefit of increasing the processing window by 48 minutes over TGPAP, an increase of 62%. Two optimised resin formulations, 100% TGPAP (100T) and a binary mix of 60% DGEBF and 40% TGPAP (60D) were taken forward to study the effects of adding a thermoplastic toughener (polyethersulphone, PES) in incremental amounts up to 50wt%. SEM images showed all toughened 100T resins had a phase separated morphology whilst all 60D resins were homogenous. The phase separation seen in 100T did not improve the matrix fracture toughness when loaded at 10 wt% and 30 wt% PES. Only when 50 wt% PES was added did fracture toughness increase in comparison to the homogenous 60D resins. Through factorial experimental design two epoxy resin formulations which excluded TGDDM were optimised with a low stoichiometric ratio. The optimum aerospace formulation is dependent on the desired processability and fracture toughness of the resin. High DGEBF-containing formulations give the longest processing windows whilst the 100% TGPAP formulation toughened with 50% PES has the highest fracture toughness.

This thesis is concerned with the new formulation of a finite-volume lattice Boltzmann equation method and its implementation on unstructured meshes. The finite-volume discretization with a cell-centered tessellation is employed. The new formulation effectively adopts a total variation diminishing concept. The formulation is analyzed for the modified partial differential equation and the apparent viscosity of the model. Further, the high-order extension of the present formulation is laid out. Parallel simulations of a variety of two-dimensional benchmark flows are carried out to validate the formulation. In Chapter 1, the important notions of the kinetic theory and the most celebrated equation in the kinetic theory, ‘the Boltzmann equation’ are given. The historical developments and the theory of a discrete form of Boltzmann equation are briefly discussed. Various off-lattice schemes are introduced. Various methodologies adopted in the past for the solution of the lattice Boltzmann equation on finite-volume discretization are reviewed. The basic objectives of this thesis are stated. In Chapter2,the basic formulations of lattice Boltzmann equation method with a rational behind different boundary condition implementations are discussed. The benchmark flows are studied for various flow phenomenon with the parallel code developed in-house. In particular, the new benchmark solution is given for the flow induced inside a rectangular, deep cavity. In Chapter 3, the need for off-lattice schemes and a general introduction to the finite-volume approach and unstructured mesh technology are given. A new mathematical formulation of the off-lattice finite-volume lattice Boltzmann equation procedure on a cell-centered, arbitrary triangular tessellation is laid out. This formulation employs the total variation diminishing procedure to treat the advection terms. The implementation of the boundary condition is given with an outline of the numerical implementation. The Chapman-Enskog (CE) expansion is performed to derive the conservation equations and an expression for the apparent viscosity from the finite-volume lattice Boltzmann equation formulation in Chapter 4. Further, the numerical investigations are performed to analyze the apparent viscosity variation with respect to the grid resolution. In Chapter 5, an extensive validation of the newly formulated finite-volume scheme is presented. The benchmark flows considered are of increasing complexity and are namely (1) Posieuille flow, (2) unsteady Couette flow, (3) lid-driven cavity flow, (4) flow past a backward step and (5) steady flow past a circular cylinder. Further, a sensitivity study to the various limiter functions has also been carried out. The main objective of Chapter6is to enhance the order of accuracy of spatio-temporal calculations in the newly presented finite-volume lattice Boltzmann equation formulation. Further, efficient implementation of the formulation for parallel processing is carried out. An appropriate decomposition of the computational domain is performed using a graph partitioning tool. The order-of-accuracy has been verified by simulating a flow past a curved surface. The extended formulation is employed to study more complex unsteady flows past circular cylinders. In Chapter 7, the main conclusions of this thesis are summarized. Possible issues to be examined for further improvements in the formulation are identified. Further, the potential applications of the present formulation are discussed.

A theoretical study is conducted for the lateral torsional buckling of wooden beam-deck assemblies consisting of twin beams braced by tongue-and-groove decking at the top. Two models are developed, each with a series of analytical and numerical solutions formulated. The first model targets twin-beam-deck assemblies where deck boards and other components are detailed to provide full continuous lateral restraint while the second model is built for situations where the beams are allowed to sway laterally and the relative lateral movement between the beams is partially restrained by the deck boards. In the first model, focus is on wind uplift while in the second model, both gravity and uplift loading scenarios are investigated. In the first model, an energy method is adopted and the principle of stationary potential energy is evoked to formulate closed-form solutions, energy-based solutions and a finite element solution. The validity of the present solutions is verified against a finite element based ABAQUS model. Similarly, a family of solutions is developed under the sway model and verified against the ABAQUS. Parametric studies are conducted for both models to examine the effects of various variables on the buckling capacity. A comparative investigation on the behavioral difference between the two models under ABAQUS is also presented. Overall, the restraining effects of deck boards bracing either on the beam compression or tension side is observed to have a significant influence on the lateral torsional buckling capacity of the twin-beam-deck assemblies.

Cette thèse porte sur le développement d’une formulation colloïdale de diminazène (DMZ) à l’aide de nanoparticules polysaccharidiques cationiques (NP+) pour le traitement de la Trypanosomiase Africaine (TA).Nous avons étudié dans un premier temps le procédé de chargement des NP+ en DMZ base. Nous avons constaté que l’ajout de phospholipides dans la matrice des NP+ est nécessaire à l’association de DMZ. La quantité de phospholipide est d’ailleurs le facteur limitant de l’indice de saturation des NP+ en DMZ. Afin de ne pas dégrader le principe actif, lors de son chargement, le procédé choisi est le « post-loading » qui correspond à un mode opératoire en conditions douces : ajout d’une solution de DMZ dans une suspension de NP+ à cœur huileux. Nos résultats montrent que cette formulation reste stable durant 6 mois à 4°C ne libérant pas de DMZ et le protégeant de l’oxydation. Dans un second temps, nous avons évalué l’efficacité thérapeutique du DMZ formulé. Les tests in vitro sur Trypanosoma brucei brucei montrent une amélioration de l’activité trypanocide du DMZ. Les tests réalisés sur un modèle aigu de TA, ont mis en évidence que la dose efficace est équivalente au DMZ libre (3 mg/kg). / This thesis focuses on the development of a colloidal formulation of diminazene (DMZ) using cationic polysaccharide nanoparticles (NP+) for the treatment of African Trypanosomiasis. We first studied the process of DMZ loading in NP+. The addition of phospholipids in the matrix of the NP+ appeared to be necessary for the DMZ association. So, the amount of phospholipids is the limiting factor of the saturation index of NP+ with DMZ. To avoid the drug degradation during its formulation, we choose the \\\"post-loading\\\" technique which corresponds to a procedure with mild conditions: adding a DMZ solution in a suspension of NP+ containing an oily core. DMZ loaded into 70DGNP+ was found to be protected against oxidation and was stable for at least 6 months at 4°C. In a second step, we evaluated the therapeutic efficacy of formulated DMZ. In vitro tests on Trypanosoma brucei brucei showed an improvement of the DMZ trypanocidal activity. Tests on an acute model of Trypanosomiasis showed that the effective dose is equivalent to the free DMZ (3 mg / kg).

Work up a strategic analysis, make external and internal analysis and prepare a strategy for future business development.

The goal of this master's thesis is to perform a strategic analysis, to formulate a strategy on its basis and to propose the way of implementation and control of the strategy for the SAP division of the Pontech s.r.o. company and to contribute to successful implementation of strategic management system in this division and company. The thesis consists of two main parts. In the first, theroretically-metodological, part the terms and theories of strategic management and strategy are explained first and then the most common tools and methods of strategic analysis and further phases of strategic cycle i.e. formulation, implementation and control, which are used in the second, analytical, part, are mentioned. The analysis of macro and microenvironment, the analysis of internal resources and capabilities and the synthesis in the form of SWOT analysis is thus performed gradually, a strategy is formulated on that basis and after all the way of implementation and control of a strategy is performed using the principles of Balanced Scorecard system.

Orientador: Mary Ann Foglio / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-22T06:18:16Z (GMT). No. of bitstreams: 1 Sousa_IlzaMariadeOliveira_M.pdf: 5880390 bytes, checksum: fd97f693a17c7170d7e33dfda63ca607 (MD5) Previous issue date: 2013 / Resumo: Arrabidaea chica (Humb. & Bonpl.) Verlot, popularmente conhecida como crajiru, espécie presente na lista de plantas medicinais de interesse ao SUS (Renisus) para o uso popular em enfermidades da pele. Estudos desenvolvidos no CPQBA-Unicamp comprovaram que o extrato bruto de A. chica possui ação cicatrizante induzindo a proliferação de fibroblastos in vitro, estimulando a síntese de colágeno in vivo e in vitro. Este estudo estabeleceu parâmetros para permitir a produção de um medicamento à base de A. chica em escala semi piloto, além de determinar condições adequadas de armazenamento, secagem e embalagem do produto final. Entre os compostos sensíveis à luz e à temperatura destaca-se a carajurina, que é responsável pela cor vermelha do extrato. A fim de aumentar a tempo de prateleira do produto microencapsulado por spray drying, utilizaram-se três materiais de parede: goma arábica (GA), goma de cajueiro (CG), e a mistura de goma arábica / maltodextrina (GM) na proporção de 1/1. Os diferentes materiais de parede apresentaram rendimentos de 82; 79 e 89,9% e teor de carajurina de 1,92%, 1 62% e 1,99%, respectivamente. Atividade antioxidante medida pelo método ORAC apresentou valores 1066,9, 1363,8 e 1026,2 uM TE / g. Os estudos de estabilidade foram realizados com extrato livre e microencapsulado armazenados em diferentes embalagens e condições. O produto armazenado a 40 ° C e 75% UR embalado em frascos de polietileno de alta densidade e saches cor de alumínio revestido de plástico diminuiu o teor de carajiruna em 10% em 20 dias de avaliação, enquanto que a embalagem de vidro foi mais estável nessas condições, diminuindo10% do conteúdo de carajiruna após 29 dias de teste. A maior meia-vida do produto microencapsulado foi de 160 dias, armazenado em saches e mantidos a 10 ° C. Todas as formulações semissólidas, avaliadas em modelos experimentais de cicatrização in vivo, foram capazes de reduzir entre 70 a 80% da área cutânea ulcerada em 10 dias de tratamento, contra 37% de redução do grupo controle no mesmo período. A estimulação da produção de colágeno para a formulação gel de Natrosol® contendo o extrato bruto livre foi de 0,093 ?g.mL-1, quando comparada com outras formulações de controle (0,019 ?g.mL-1) e bases (0,028 ?g.mL-1) / Abstract: Arrabidaea chica (Humb. & Bonpl.) Verlot specie, popularly known as Crajiru, included in the National List of interest to SUS (Renisus) is reported to have healing properties for skin ailments. Studies conducted in CPQBA-UNICAMP showed that the crude extract of this plant species induced fibroblast proliferation in vitro, stimulating collagen synthesis in vivo and in vitro. This study established parameters to enable the production of an herbal medicine in semi pilot scale. The drying, storage and packaging conditions were evaluated to determine the best suited to the product. Among the compounds sensitive to light and temperature is carajurin, responsible for the extract's red color. In order to increase product's shelf half-life microencapsulation by spray drying using three different wall materials, arabic gum (GA), cashew gum (CG) and the mixture of arabic gum / maltodextrin (GM) the ratio of 1/1 were evaluated. The different wall materials provided 82.0, 79.0 and 89.9% yields respectively, with carajurin content of 1.92%, 1 62%, and 1.99%. Antioxidant activity measured by the ORAC method gave 1066.9, 1363.8 and 1026.2 ?M TE / g values. Stability studies were conducted with spray dried EB stored in different containers and conditions. The product stored at 40 ° C and 75% RH packed in high density polyethylene and sachets plastic coated aluminum color decreased 10% carajirun content throughout the 20 days period of evaluation. Whereas the glass container was more stable under these conditions, leading to10% decreases in carajirun content throughout 29 days. The greatest half-life of 160 days was verified when the product was stored in sachets at 10 ° C. The semi-solid formulations for topical use containing EB proposed in this study with Carbopol ¿ gel, Natrosol ¿ gel Cream A / O (free and microencapsulated), Cream O / A (free and microencapsulated), evaluated in experimental models of wound healing in vivo reduced 80-70% the ulcerated skin area after 10 days of treatment, whereas the control group decreased by 37%. Collagen concentration observed for the animals treated with Natrosol ¿ gel 2,5% A. chica was 0.093 ?g.mL-1, while animals treated with saline had collagen production of 0.019 ?g.mL-1 and Natrosol ¿ base gel concentration showed 0.028?g.mL-1 / Mestrado / Fármacos, Medicamentos e Insumos para Saúde / Mestra em Biociências e Tecnologia de Produtos Bioativos

O problema de balanceamento de linhas de produção e designação de trabalhadores (ALWABP, do inglês Assembly Line Worker Assignment and Balancing Problem ) é uma extensão do problema simples de balanceamento de linhas na qual os tempos de execução de tarefas são dependentes dos trabalhadores. Este problema tem sua motivação prática oriunda de linhas de produção com trabalhadores deficientes. Neste trabalho, focamos em uma extensão para o problema que permite lidar com a possibilidade de layouts de linhas com estações em paralelo. Além disso, estudamos uma segunda variante do problema que permite que os trabalhadores colaborem uns com os outros em uma mesma estação. Apresentamos formulações matemáticas para ambas as versões do problema. Adicionalmente, a partir de adaptações de métodos existentes para o ALWABP serial, desenvolvemos heurísticas construtivas para o ALWABP paralelo e ALWABP colaborativo. Testes computacionais em instâncias da literatura e uma análise detalhada dos resultados são apresentados / The assembly line and worker assignment balancing problem is an extension of the classical simple assembly line balancing problem where task execution times are workerdependent. This problem is motivated by the situation faced when balancing assembly lines with disabled workers. In this study, we focus on an extension for the problem with the goal of including the possibility of having layouts with parallel workstations. We also study a second variation for this problem that allows workers collaborating with each other. We present mathematical formulations for both problems. Moreover, constructive heuristics are developed, based on heuristic methods for the serial assembly line worker assignment and balancing problem. Computational tests on literature instances and a detailed analysis of the results are reported

This dissertation focuses on developing 3D printing as a fabrication method for microfluidic devices. Specifically, I concentrate on the 3D printing approach known as Digital Light Processing stereolithography (DLP-SLA) in which serially projected images are used to sequentially photopolymerize layers to build a microfluidic device. The motivation for this work is to explore a much faster alternative to cleanroom-based microfabrication that additionally offers the opportunity to densely integrate microfluidic elements in compact 3D layouts for dramatic device volume reduction. In the course of my research, an optical approach was used to guide custom resin formulation to help create the interconnected hollow regions that form a microfluidic device. This was based on a new a mathematical model to calculate the optical dose delivered throughout a 3D printed part, which also explains the effect of voids. The model was verified by a series of 3D printed chips fabricated with a commercial 3D printer and a custom resin. Channels as small as 108 µm x 60 µm were repeatably fabricated. Next, highly compact active fluidic components, including valves, pumps, and multiplexers, were fabricated with the same 3D printer and resin. The valves achieved a 10x size reduction compared with previous results, and were the smallest 3D printed valves at the time. Moreover, by adding thermal initiator to thermally cure devices after 3D printing, the durability of 3D printed valves was improved and up to 1 million actuations were demonstrated.To further decrease the 3D printed feature size, I built a custom 3D printer with a 385 nm LED light source and a 7.56 µm pixel pitch in the plane of the projected image. A custom resin was also developed to take advantage of the new 3D printer's features, which necessitated developing a UV absorber screening process which I applied to 20 candidate absorbers. In addition, a new mathematical model was developed to use only the absorber's molar absorptivity measurement to predict the resin optical penetration depth, which is important for determining the z-resolution that can be achieved with a given resin. The final resin formulation uses 2-nitrophenyl phenyl sulfide (NPS) as the UV absorber. With this resin, along with a new channel narrowing technique, I successfully created flow channel cross sections as small as 18 µm x 20 µm.With the custom 3D printer, smaller valves and pumps become possible, which led to the invention of a new method of creating large numbers of high density chip-to-chip microfluidic interconnects based on either simple integrated microgaskets (SIMs) or controlled-compression integrated microgaskets (CCIMs). Since these structures are directly 3D printed as part of a device, they require no additional materials or fabrication steps. As a demonstration of the efficacy of this approach, 121 chip-to-chip interconnects in an 11 x 11 array for both SIMs and CCIMs with an areal density of 53 interconnects per square mm were demonstrated, and tested up to 50 psi without leaking. Finally, these interconnects were used in the development of 3D printed chips with valves having 30x smaller volume than the valves we previously demonstrated. These valves served as a building block for demonstrating the miniaturization potential of an active fluid mixer using our 3D printing tools, materials, and methods. The mixer provided a set of selectable mixing ratios, and was designed in 2 configurations, a linear dilution mixer-pump (LDMP) and a parallelized dilution mixer-pump (PDMP), which occupy volumes of only 1.5 cubic mm and 2.6 cubic mm, respectively.

The overarching objective of this thesis is to demonstrate a systematic approach for addressing the instability issues associated with low limit degradants by developing quantitative degradation models that incorporate key instability determinants into predictive equations. Chlorhexidine was used as model compound in aqueous solution to demonstrate the application of the predictive models to issues of formulation design and manufacturing. Chorhexidine degrades to p-chloroaniline, a well-established toxicant, by various pH-dependent pathways. In acidic conditions, the direct formation of p-chloroaniline from chlorhexidine is the major pathway whereas the indirect formation of p-chloroaniline via p-chlorophenylurea is the main alkaline pathway. Rate laws and mechanisms for each pathway were presented. Shelf life predictions equations for chlorhexidine formulations were derived based on the kinetics of p-chloroaniline appearance as a function of formulation strength, solution pH, bulk chlorhexidine purity and storage temperature. The pH range for optimal shelf-life was 5.0 to 5.5. Simple extraction procedures used during formulation preparation were identified to improve bulk chlorhexidine purity and thereby extend product shelf-life. Gabapentin degrades directly to gabapentin-lactam in the solid-state. The established limit on gabapentin-lactam in gabapentin pharmaceutical formulations is <0.5% w/w thus gabapentin instability was studied as a model compound for solid state formulation applications. Mechanical stress associated with drug product manufacturing in unit operations such as milling increased the subsequent lactamization rate upon storage due to increased gabapentin crystal disorder. The effect of environment moisture was to decrease the rate of gabapentin-lactam formation due to competitive recovery of gabapentin crystallinity which was accelerated by humidity. A degradation model that combined both physical and chemical instability pathways including autocatalytic branching, spontaneous intra-molecular cyclization and moisture-induced physical transformation steps was shown to be consistent with lactamization kinetics as a function of both environmental (temperature and humidity) and manufacturing-related effects. This kinetic model was used to predict the shelf-life of gabapentin tablets prepared under various exemplary manufacturing conditions thereby demonstrating the ability of the model to link manufacturing variation and shelf-life stability in for solid-state drug formulations.