Esta investigación, que pretende continuar y actualizar la realizada en mi TFM de COMINCREA (Master oficial de comunicación e industrias creativas de la Universidad de Alicante) sobre la viabilidad de la sección de cine de las tiendas FNAC con la digitalización de contenidos, analiza el modelo de negocio de Netflix en España y sus estrategias empresariales para la consolidación de su producto digital. El inesperado éxito del mismo, superando con creces las pesimistas expectativas de los estudios académicos previos a su llegada, ha intensificado las profundas transformaciones en la producción, distribución y consumo de los productos audiovisuales de entretenimiento, poniendo en serio peligro el futuro del formato físico y las tiendas dedicadas a su venta. Dichas estrategias emergen, en realidad, como una optimización de las utilizadas en el pasado por las propias tiendas, por lo que se indaga en la viabilidad de que dichas tiendas físicas y mixtas (las que ofertan también venta online de dicho producto físico) puedan, a su vez, implementar (de manera mejorada y adaptada) dichas estrategias con el objetivo de seguir siendo un negocio viable.

Social media and user engagement are bigger than ever. Users are presented with various types of content curated by algorithms, which partially dictate what is shown to them. These algorithms lack transparency and clarity for the user. In this thesis we have developed a toolset to tail fit data of user engagement to show what behaviours this data actually shows. We want to see the differences between categories of content and show how user engagement in social media behaves. From our study we have found that there are differences between how users engage with different leanings within political content andcontents of differing credibility. We have also found that more narrow metrics in choosingdata can present different results and behaviours. From this we can determine that choice of data is crucial when working with tails. Future work is imperative to keep creating understanding for these social media platforms and how users engage with different types of content. To keep up with the constantly changing environment of social media new tools and methods will needed to create understanding for our most used platforms for public interaction.

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Asset allocation is the most influential factor driving investment performance. While researchers have made substantial progress in the field of asset allocation since the introduction of mean-variance framework by Markowitz, there is little agreement about appropriate portfolio choice for multi-period long horizon investors. Nowhere this is more evident than trustees of retirement plans choosing different asset allocation strategies as default investment options for their members. This doctoral dissertation consists of four essays each of which explores either a novel or an unresolved issue in the area of asset allocation for individual retirement plan participants. The goal of the thesis is to provide greater insight into the subject of portfolio choice in retirement plans and advance scholarship in this field. The first study evaluates different constant mix or fixed weight asset allocation strategies and comments on their relative appeal as default investment options. In contrast to past research which deals mostly with theoretical or hypothetical models of asset allocation, we investigate asset allocation strategies that are actually used as default investment options by superannuation funds in Australia. We find that strategies with moderate allocation to stocks are consistently outperformed in terms of upside potential of exceeding the participant’s wealth accumulation target as well as downside risk of falling below that target by very aggressive strategies whose allocation to stocks approach 100%. The risk of extremely adverse wealth outcomes for plan participants does not appear to be very sensitive to asset allocation. Drawing on the evidence of the previous study, the second essay explores possible solutions to the well known problem of gender inequality in retirement investment outcomes. Using non-parametric stochastic simulation, we simulate iv and compare the retirement wealth outcomes for a hypothetical female and male worker under different assumptions about breaks in employment, superannuation contribution rates, and asset allocation strategies. We argue that modest changes in contribution and asset allocation strategy for the female plan participant are necessary to ensure an equitable wealth outcome in retirement. The findings provide strong evidence against gender-neutral default contribution and asset allocation policy currently institutionalized in Australia and other countries. In the third study we examine the efficacy of lifecycle asset allocation models which allocate aggressively to risky asset classes when the employee participants are young and gradually switch to more conservative asset classes as they approach retirement. We show that the conventional lifecycle strategies make a costly mistake by ignoring the change in portfolio size over time as a critical input in the asset allocation decision. Due to this portfolio size effect, which has hitherto remained unexplored in literature, the terminal value of accumulation in retirement account is critically dependent on the asset allocation strategy adopted by the participant in later years relative to early years. The final essay extends the findings of the previous chapter by proposing an alternative approach to lifecycle asset allocation which incorporates performance feedback. We demonstrate that strategies that dynamically alter allocation between growth and conservative asset classes at different points on the investment horizon based on cumulative portfolio performance relative to a set target generally result in superior wealth outcomes compared to those of conventional lifecycle strategies. The dynamic allocation strategy exhibits clear second-degree stochastic dominance over conventional strategies which switch assets in a deterministic manner as well as balanced diversified strategies.

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Flutter is one of the primary aeroelastic phenomena that must be considered in aircraft design. Flutter is a self-sustaining structural vibration in which energy is extracted from the air flow and transferred to the structure. The amplitude of the vibration grows exponentially until structural failure occurs. Flutter stability requirements often influence the design of an aircraft, making accurate flutter prediction capabilities an essential part of the design process. Advances in computational fluid dynamics and computational power make it possible to solve the fluid flow and structural dynamics simultaneously, providing highly accurate solutions especially in the transonic flow regime. This procedure is, however, too time-consuming to be used in the design optimisation process. As a result panel codes, e.g., the doublet lattice method, and modal-based structural analysis methods are still being used extensively and continually improved. One application that is lagging in terms of accuracy and simplicity (from the user’s perspective) is the flutter analysis of T-tails. The flutter analysis of a T-tail usually involves the calculation of additional aerodynamic loads, apart from the loads calculated by the standard unsteady aerodynamic codes for conventional empennages. The popular implementations of the doublet lattice method do not calculate loads due to the in-plane motion (i.e., lateral or longitudinal motion) of the horizontal stabiliser or the in-plane loads on the stabiliser. In addition, these loads are dependent on the steady-state load distribution on the stabiliser, which is ignored in the doublet lattice method. The objective of the study was to extend the doublet lattice method to calculate the additional aerodynamic loads that are crucial for T-tail flutter analysis along with the customary unsteady air loads for conventional configurations. This was achieved by employing the Kutta-Joukowski theorem in the calculation of unsteady air loads on lifting surface panels. Calculating the additional unsteady air loads for T-tails within the doublet lattice method significantly reduces the human effort required for T-tail flutter analysis as well as the opportunities for introducing errors into the analysis. During the course of the study it became apparent that it was necessary to consider the quadratic mode shape components in addition to the linear mode shape components. Otherwise the unsteady loads due to the rotation (“tilting”) of the steady-state load on the stabiliser, one of the additional aerodynamic loads that are crucial for T-tail flutter analysis, would give rise to spurious generalised forces. In order to reduce the additional burden of determining the quadratic mode shape components, methods for calculating quadratic mode shape components using linear finite element analysis or estimating them from the linear mode shape components were developed. Wind tunnel tests were performed to validate the proposed computational method. A T-tail flutter model which incorporated a mechanism for changing the incidence angle of the horizontal stabiliser, and consequently the steady-state load distribution on the horizontal stabiliser, was used. The flutter speed of this model as a function of the horizontal stabiliser incidence was determined experimentally and compared to predictions. Satisfactory correlation was found between predicted and experimentally determined flutter speeds. / Thesis (M.Ing. (Chemical Engineering))--North-West University, Potchefstroom Campus, 2012

Serotonin receptors play a variety of functional roles in the body. Some indications and treatment claims for one of the classes of serotonin receptors, the 5-HT3 receptor family, include: anxiety, depression, chemotherapy- and radiation-induced emesis, constipation, irritable bowel syndrome, pain, drug addiction, and satiety control. A 5-HT3 receptor partial agonist, MD-354, served as a lead compound in the development of new 5-HT3 receptor ligands. Using halogenated analogs the study investigated their effect on binding to the 5-HT3 receptor. Conformationally-constrained analogs (quinazolines) were shown to be a novel class of 5-HT3 receptor antagonists. The log P values were determined for several analogs, and indicated that these ligands should be able to penetrate the blood-brain barrier. A homology model of the 5-HT3 receptor was built and the docking modes were assessed for these two series. Quinazolines were investigated for antidepressant properties using the mouse tail suspension test, and were shown to possess antidepressant-like activity.

The Dukat laboratory developed 2-amino-6-chloro-3,4-dihydroquinazoline (A6CDQ) as a 5-HT3 receptor ligand. A6CDQ and one of its positional isomers, the 7-chloro analog A7CDQ, produced antidepressant-like effects in the mouse tail suspension test (TST). We investigated and systematically ruled out a solely 5-HT3 receptor or hSERT mediated mechanism of antidepressant-like effect for both A6CDQ and A7CDQ. The role of organic cation transporter 3 (OCT3) as an alternative mechanism in the regulation of neurotransmitters including serotonin (5-HT) and the therapeutic potential of targeting hOCT3 to achieve antidepressant effects has been established. By virtue of possessing protonatable nitrogen atoms, 2-aminodihyroquinazolines could potentially exhibit activity at OCT3. A major goal of our present study was to explore the non-serotonergic mechanism of antidepressant-like effects and to study the as yet unexplored structure-activity-relationships (SARs) at OCT3. We examined the role of i) the chloro group, ii) the methylene bridge and iii) electronic/lipophilic effects at the 6-position. We developed the first 3-D homology models of both the human and mouse orthologs of OCT3, conducted docking studies and HINT analysis, and identified critical amino acid residues interacting with 2-aminodihydroquinazoline analogs at hOCT3 and mOCT3. Retention of antidepressant-like activity in the mouse and potential locomotor stimulant effects for TST-active doses were thoroughly investigated. We have successfully investigated initial SAR of 2-aminodihydroquinazolines at hOCT3 and generated the first 3-D homology models of hOCT3 and mOCT3. Highly potent and selective compounds could potentially be developed as radioligands to probe the binding site of OCT3 and as a mechanistically novel class of antidepressants.

A remodelação óssea pode ser estimulada por forças mecânicas presentes nas atividades físicas normais. Mas, a diminuição dos estímulos mecânicos, observada em vôos espaciais (exposição dos astronautas ao ambiente de microgravidade), nas imobilizações ortopédicas e na permanência prolongada de pacientes no leito, pode causar danos significativos na estrutura óssea. Neste caso, aumenta o risco de fraturas, não durante o período de sub-carregamento, mas no retorno às atividades físicas normais. A contra medida mais estudada para evitar danos ou promover a recuperação da estrutura óssea, é o exercício físico. Portanto, um dos objetivos desta pesquisa surgiu do interesse em analisar mecanicamente e microscopicamente fêmures de ratos submetidos à hipocinesia e posterior treinamento em esteira. Outro objetivo surgiu da necessidade de desenvolver metodologias mais precisas de análises mecânicas em ossos longos de ratos. Foram utilizadas 66 ratas da raça Wistar. Os animais foram criados até a idade de 90 dias, para o início dos procedimentos experimentais. Eles foram divididos em cinco grupos, sendo dois controles e três experimentais. Os animais do grupo Cont I foram criados até completarem 118 dias de idade e serviu de controle para o grupo S (suspenso), que consistiu em suspender os animais pela cauda por 28 dias. Já no grupo Cont II os animais foram criados até 139 dias e foi o controle para os grupos S-L (suspenso e liberado) e S-T (suspenso e treinado). No grupo S-L os animais foram liberados por 21 dias, após o período de suspensão pela cauda. No grupo S-T os animais passaram por um protocolo de treinamento em esteira por 21 dias após a suspensão pela cauda. Foram analisadas algumas propriedades mecânicas do terço proximal do fêmur esquerdo e da diáfise do fêmur direito. Outra análise realizada foi a microscópica, por meio de fluorescência óssea da região do terço proximal do fêmur direito e da região da diáfise do fêmur esquerdo. A suspensão pela cauda provocou diminuição das propriedades mecânicas do terço proximal do fêmur dos animais, apesar de não apresentar diferença visível na análise microscópica. A liberação após a suspensão causou alterações no núcleo de ossificação, na esfericidade da cabeça e na placa de crescimento do terço proximal do fêmur, sem alterar o comportamento mecânico desta região. E o treinamento conservou o núcleo de ossificação e a esfericidade da cabeça após a suspensão, e também, não alterou o comportamento mecânico. A ossificação periosteal na diáfise do fêmur dos animais suspensos diminuiu, no grupo S-L foi mais acentuada no endósteo e, no grupo S-T o treinamento promoveu a recuperação do balanço osteogênico. A liberação promoveu a recuperação parcial do comportamento mecânico do osso cortical da diáfise do fêmur do rato e, o treinamento recuperou as propriedades e estimulou a formação de osso novo. / Bone remodeling can be stimulated by the mechanical solicitation from normal physical activities. Consequently, decreasing of mechanical stimuli as occurring during spatial flights, prolonged bed rest and orthopedic immobilization may cause significant weakening of the bone structure. In such cases there is an increased risk of fractures when the normal physical activities are resumed. Physical exercises are a way to try to strengthen the bone structure. Therefore, in the present research we investigated the mechanical behavior and microscopy analysis of long bones from rats that were previously maintained in tail suspension and later, submitted to physical exercise in a treadmill. An additional aim came up from the necessity to develop more precise technologies that mechanical testing in long bones of rats. Sixty-six Wistar rats were used. Firstly, the animals were raised until the age of ninety days and the divided into five groups (two controls and three experimental). The animals allocated to control I were killed at 118 days of age. In the groups S, the animals were tail suspended during 28 days. In the control group II the animals were killed at 139 days of age. In group S-R (suspended and released) the rats were keep free for 21 days after the tail suspension. In group S-T (suspended and trained) after the tail suspension period the rats were trained in treadmill during 21 days. The mechanical properties of the whole proximal third of the femur were analyzed in flexion-compression on one side and from the opposite side femur bone samples were harnested for three-point bending tests. Furthermore, the osteogeneses in different groups were studied at the mid-diaphysis of the femur and at the proximal femoral epiphysis with oxitetracycline. The suspension caused a decrease of the mechanical properties of the proximal femur. Resuming free activities in cage after the suspension period caused flattening of the femoral head and earlier closure of the growth plate, but no difference of the mechanical behavior was detected. Conversely, the treadmill training caused no alteration in the femoral head shape, but the mechanical properties did not change. The fluorescence studies showed that there was a decrease of the osteogenic activity at the subperiosteal level in suspended animals, but for suspended-released rats the diminished activity occurred at the endosteal level. The treadmill training caused recovering of the osteogenic balance. The post-suspension released in cage promoted partial recovery of the mechanical properties of the diaphyseal bone and the treadmill training besides recovering the normal mechanical properties did stimulate the new-bone formation.