Society relies more and more on a continuous supply of electricity. However, while underinvestments in reliability lead to an unacceptable number of power interruptions, overinvestments result in too high costs for society. To give incentives for a socioeconomically optimal level of reliability, quality regulations have been adopted in many European countries. These quality regulations imply new financial risks for the distribution system operator (DSO) since poor reliability can reduce the allowed revenue for the DSO and compensation may have to be paid to affected customers.This thesis develops a method for evaluating the incentives for reliability investments implied by different quality regulation designs. The method can be used to investigate whether socioeconomically beneficial projects are also beneficial for a profit-maximizing DSO subject to a particular quality regulation design. To investigate which reinvestment projects are preferable for society and a DSO, risk-based methods are developed. With these methods, the probability of power interruptions and the consequences of these can be simulated. The consequences of interruptions for the DSO will to a large extent depend on the quality regulation. The consequences for the customers, and hence also society, will depend on factors such as the interruption duration and time of occurrence. The proposed risk-based methods consider extreme outage events in the risk assessments by incorporating the impact of severe weather, estimating the full probability distribution of the total reliability cost, and formulating a risk-averse strategy. Results from case studies performed show that quality regulation design has a significant impact on reinvestment project profitability for a DSO. In order to adequately capture the financial risk that the DSO is exposed to, detailed risk-based methods, such as the ones developed in this thesis, are needed. Furthermore, when making investment decisions, a risk-averse strategy may clarify the benefits or drawbacks of a project that are hard to discover by looking only at the expected net present value. / QC 20110530

Architecting e-business applications is a complex design activity. This is mainly due to the numerous architectural decisions to be made, including the selection of alternative technologies, software components, design strategies, patterns, standards, protocols, platforms, etc. Further complexities arise due to the fact that these alternatives often vary considerably in their support for different quality attributes. Moreover, there are often different groups of stakeholders involved, with each having their own quality goals and criteria. Furthermore, different architectural decisions often include interdependent alternatives, where the selection of one alternative for one particular decision impacts the selections to be made for alternatives from other different decisions. There have been several research efforts aiming at providing sufficient mechanisms and tools for facilitating the architectural evaluation and design process. These approaches, however, address architectural decisions in isolation, where they focus on evaluating a limited set of alternatives belonging to one architectural decision. This has been the primary motivation behind the development of the Architectural DEcision-Making Support (ADEMS) framework, which basically aims at supporting stakeholders and architects during the architectural decision-making process by helping them determining a suitable combination of architectural alternatives. ADEMS framework is an iterative process that leverages rigorous quantitative decision-making techniques available in the literature of Management Science, particularly Multiple Attribute Decision-Making (MADM) methods and Integer Programming (IP). Furthermore, due to the number of architectural decisions involved as well as the variety of available alternatives, the architecture design space is expected to be huge. For this purpose, a query language has been developed, known as the Architecture Query Language (AQL), to aid architects in exploring and analyzing the design space in further depth, and also in examining different ???what-if??? architectural scenarios. In addition, in order to support leveraging ADEMS framework, a support tool has been implemented for carrying out the sophisticated set of mathematical computations and comparisons of the large number of architectural combinations, which might otherwise be hard to conduct using manual techniques. The primary contribution of the tool is in its help to identify, evaluate, and rank all potential combinations of alternatives based on their satisfaction to quality preferences provided by the different stakeholders. Finally, to assess the feasibility of ADEMS, three different case studies have been conducted relating to the architectural evaluation of different e-business and enterprise applications. Results obtained for the three case studies were quite positive as they showed an acceptable accuracy level for the decisions recommended by ADEMS, and at a reasonable time and effort costs for the different system stakeholders.

München: Auf dem Messegelände findet eine Audi Management Konferenz (MMK) in statt. Das Audi Journal berichtet zum ersten Mal von der MMK. Der Aufbruch: Rupert Stadler – der Vorstandsvorsitzende der AUDI AG – zeichnet in seiner Rede ein Bild über den Weg in die Zukunft. Die Themenschwerpunkte: digital, global, ultra, premium – was steckt dahinter? (AUDI AG 2014)

En la actualidad, el negocio de lavanderías a nivel nacional ha ido innovando en el transcurso de los últimos años, ya que gracias a la tecnología y a las nuevas tendencias del mercado se ha podido dar un giro al servicio tradicional al cual se estaba acostumbrado. En este caso, existen herramientas tecnológicas como los aplicativos móviles, los cuales se han adaptado para el modelo de negocio de lavanderías simplificándole la vida al consumidor, ya que existen diversas variables como la falta de tiempo para trasladarse a una tienda de servicio y el horario de trabajo de los potenciales clientes que les impide llegar a tiempo a dejar o recoger la ropa. De esta manera, el tema de investigación consiste en analizar las relaciones entre los factores de uso, tales como: el nivel de entendimiento del usuario, la calidad del sistema y la calidad del diseño de los aplicativos móviles en el servicio de lavanderías en Lima Metropolitana. A través de un estudio cualitativo y cuantitativo, se buscará evidenciar y demostrar que existe una relación y es relevante para el negocio de lavanderías por un aplicativo en la ciudad de Lima, Perú. / Currently, the laundry business nationwide has been innovating in recent years, since thanks to technology and new market trends it has been possible to turn the traditional service to which it was accustomed. In this case, there are technological tools such as mobile applications, which have been adapted for the laundry business model, making life easier for the consumer, since there are various variables such as the lack of time to go to a service store and the schedule of potential customers that prevents them from being on time to drop off or pick up clothes. In this way, the research topic consists of analyzing the relationships between the use factors, such as: the level of user understanding, the quality of the system and the quality of the design of mobile applications in the laundry service in Metropolitan Lima. . Through a qualitative and quantitative study, it will seek to demonstrate and demonstrate that a relationship exists and is relevant to the laundry business by an application in the city of Lima, Peru. / Trabajo de investigación

Background: Nowadays, the development of the internet makes online shopping more popularized . The appearance of online shopping brings considerable benefits to customers, however, there are still risks in the area. To maintain good relationship management between customers and companies, it is necessary to understand the online customer experience and its relevant important factors . Purpose: The purpose of this study is to explain the impact of three factors (low-quality delivery, low-quality online customer service, and low-quality website design) on online customer experience. Methodology: The paper used a quantitative approach in cross-sectional design and collected totally 78 responses. The related data collection is conducted through a self-completion questionnaire in the online form.  Findings: The negative impacts of low-quality online customer service and low-quality website design on online customer experience are confirmed. There is an effective and strong connection between low-quality website design and low-quality online customer service. Conclusion: Based on the findings, H2 and H3 cannot be rejected but H1 needs to be rejected. One can therefore say that even in the context of rapid technological development, modern online shoppers have not changed their aversion to low-quality elements, that the view that low-quality online customer service and low-quality website design negatively affect OCE has not changed.

Para efetivamente tratar uma infecção, é necessário que o antibiótico possua atividade antimicrobiana adequada e seja capaz de inibir o crescimento do microrganismo patogênico. O doseamento microbiológico é uma metodologia indicada para a análise do antimicrobiano de forma simples, quando comparado com outras metodologias. A Food and Drug Administration (FDA) tem encorajado uma abordagem proativa para introduzir inovações e benefícios associados ao processo de produção farmacêutica. A Qualidade por Design Analítico (AQbD) ajuda no desenvolvimento de métodos analíticos robustos e de baixo custo, que são aplicáveis durante todo ciclo de vida do produto. Os métodos microbiológicos tradicionais, de forma geral, apresentam baixa reprodutibilidade e alta incerteza. Desta forma, justifica-se o desenvolvimento de métodos microbiológicos alternativos para a análise de antimicrobianos empregando-se os conceitos de Qualidade por Design Analítico, com a finalidade de melhorar a reprodutibilidade e reduzir a incerteza final. O objetivo deste trabalho foi aplicar o conceito de Qualidade por Design Analítico (AQbD) no desenvolvimento de método colorimétrico para análise de sulfato de neomicina. O sulfato de neomicina é um antimicrobiano aminoglicosídeo amplamente empregado no tratamento de infecções cutâneas ou mucosas, tais como queimaduras, úlceras, e dermatites infecciosas. Métodos cromatográficos como a cromatografia líquida de alta eficiência em fase reversa, de pareamento iônico ou cromatografia iônica com derivatização (pré ou pós-coluna) são utilizados para a análise de aminoglicosídeos, inclusive sulfato de neomicina. Contudo, de acordo com as farmacopeias, o método microbiológico é o método analítico de escolha para a análise de sulfato de neomicina e outros aminoglicosídeos. A análise colorimétrica é um método amplamente utilizado para a detecção e quantificação de diferentes substâncias, incluindo o crescimento microbiano em estudos de eficácia terapêutica. Neste trabalho, propomos o uso de resazurina como marcador colorimétrico. O indicador sofre uma reação de oxido-redução na qual altera a coloração em resposta à redução química resultante do crescimento celular. O uso de microplacas para a análise colorimétrica é uma alternativa ao método realizado em tubos de ensaio. Uma alternativa ao uso de espectrofotômetros para a análise colorimétrica é o uso de aparelhos smartphones, pois são equipados com CPUs rápidas, câmeras de alta resolução e sensores de imagem. O processamento da imagem captada pela câmera do dispositivo é utilizado como um analisador colorimétrico. Portanto, a aplicação dos conceitos de Qualidade por Design Analítico (AQbD) possibilitou o desenvolvimento racional de método microbiológico colorimétrico para análise de sulfato de neomicina. / To effectively treat an infection, the antibiotic must have adequate antimicrobial activity and be capable of inhibiting the growth of the pathogenic microorganism. The microbiological assay is an indicated methodology for the analysis of the antimicrobial in a simple way, when compared with other methodologies. The Food and Drug Administration (FDA) has encouraged a proactive approach to introducing innovations and benefits associated with the pharmaceutical production process. Analytical Design Quality (AQbD) assists in the development of robust, low cost analytical methods that are applicable throughout the product life cycle. Traditional microbiological methods, in general, have low reproducibility and high uncertainty. Thus, it is justified the development of alternative microbiological methods for the analysis of antimicrobials using the concepts of Quality by Analytical Design, in order to improve reproducibility and reduce final uncertainty. The objective of this work was to apply the concept of Quality by Analytical Design (AQbD) in the development of a colorimetric method for the analysis of neomycin sulfate. Neomycin Sulfate is an aminoglycoside antimicrobial widely used in the treatment of cutaneous or mucosal infections, such as burns, ulcers, and infectious dermatitis. Chromatographic methods such as reverse phase high performance liquid chromatography, ion-pairing or ion chromatography with derivatization (pre or post-column) are used for the analysis of aminoglycosides, including neomycin sulfate. However, according to pharmacopoeias, the microbiological method is the analytical method of choice for the analysis of neomycin sulphate and other aminoglycosides. Colorimetric analysis is a widely used method for the detection and quantification of different substances, including microbial growth in studies of therapeutic efficacy. In this work, we propose the use of resazurin as a colorimetric marker. The indicator undergoes an oxidation-reduction reaction in which it alters the coloration in response to the chemical reduction resulting from cell growth. The use of microplates for colorimetric analysis is an alternative to the method carried out in test tubes. An alternative to the use of spectrophotometers for colorimetric analysis is the use of smartphones because they are equipped with fast CPUs, high resolution cameras and image sensors. The image processing captured by the device\'s camera is used as a colorimetric analyzer. Therefore, the application of the concepts of Quality by Analytical Design (AQbD) allowed the rational development of a microbiological colorimetric method for analysis of neomycin sulfate.

Os protetores solares (PS) são os grandes responsáveis pela proteção da pele quando exposta à radiação solar, por isso a importância sanitária de se otimizar o desenvolvimento deste cosmético tipo II e monitorar para que seja eficaz em seu propósito. O principal objetivo deste trabalho é aplicar os conceitos de Qualidade por Design (QbD), ferramentas estatísticas de desenho experimental (DoE - Design of Experiments) e o conceito de tecnologia analítica de processo (PAT - Process Analytical Technology) para desenvolver uma formulação e processo produtivo de um PS de modo a modernizar os processos da indústria cosmética, fazendo as análises durante o processo e eliminando o controle de qualidade final. Trata-se de um sistema de desenvolvimento sistematizado, onde se executa as ferramentas de QbD para avaliar os dados obtidos ao longo da fase experimental. Para a fase experimental, empregou-se o desenho fatorial e desenho do compósito central (CCD - Central Composite Design) como ferramenta estatística, para a execução do planejamento de experimentos (DoE - Design of Experiments). As respostas foram analisadas através da metodologia de superfície resposta (RSM - Response Surface Methodology). Tais ferramentas são fundamentais para a determinação do desenho de concepção (design space), para se obter o PS com as melhores características físico-químicas e de processo dentro do escopo delineado. Para o desenvolvimento da metodologia de análise in line, optou-se pela utilização da espectrometria UV, utilizando-se ferramentas como análise de regressão dos mínimos quadrados (PLS) devido a praticidade em transforma-la em uma ferramenta PAT, para isto, a quimiometria foi empregada para modelar sistemas que são desconhecidos e complexos, como um PS, e trazendo respostas diretas como a aprovação do produto antes de ser embalado, por exemplo. A abordagem apresentada baseia-se na construção da qualidade ao longo do desenvolvimento e otimização de PS e torna possível o monitoramento da qualidade em tempo real. / The sunscreens are great responsible for the skin protection when it is exposed to direct sunlight, so it means a great importance of health to optimize the development of type II cosmetic and monitor for it to be effective in its purpose. The objective of this work is to apply the concepts of Quality by Design and statistical tools of experimental design (DoE - Design of experiments), as well as applying the process analytical technology (PAT - Process Analytical Technology) concept for formulation and manufacturing process development of a topical sunscreen being able to modernize the cosmetic industry processing, including real time analyses and eliminating quarantine step, which waits analysis approval performed by the quality assurance, and then release the product for sale. As it is a systematic development, where critical quality attributes and risk assessment were performed to evaluate over obtained data. During experimental phase, the factorial design was used as a statistical tool for design of experiments implementation, and the responses were analyzed by response surface methodology (RSM - Response Surface Methodology). This mapping is critical to determination of the product design (design space), i.e. get sunscreen with the best physical and chemical characteristics and processing within the outlined scope. For in line methodology development, UV spectrometry was opted to be used due to less effort in sample preparation and due to great easiness to turn it into a PAT tool. For this, chemometrics was used, which brings together chemical and statistical elements to obtain three main elements: empirical modeling, multivariate modeling and chemical data, making it able to model systems that are unknown and complex, as a sunscreen, getting direct answers as product release approval before being packed, for example. The presented approach was based on the construction of quality throughout the sunscreen development and optimization making possible the real time quality monitoring.

Human tissue banks are a potential source of cellular material for the emerging cellbased therapy industry; umbilical cord tissue (UCT) private banking is increasing in such facilities as a source of mesenchymal stem cells for future therapeutic use. However, early handling of UCT is relatively uncontrolled due to the clinical demands of the birth environment and subsequent transport logistics. It is therefore necessary to develop extraction methods that are robust to real world operating conditions,rather than idealised operation. This will be critical for all processes using primary tissue or cell sources. The research work undertaken in this PhD project was initiated by the collaboration with one of the leading private cord blood banks in the UK and later driven by the prospect of expanding the cell therapy and business potential of the bank. The investigation described in this thesis has focused on: - Developing an extraction method for human mesencymal stem cells (hMSCs) from UCT. - Understanding and minimizing the noticed variability in cell yield extracted from UCT by mapping the operating environment and assessing the risk factors before empirically determining their effect on the process. - Establishing the necessary process controls in the production of high quality hMSCs, through a series of wet experiments, targeted at narrowing down the sources of variability down to sub-process level. - Finding a novel method for assessing the cell content and viability of cords prior to processing. Therefore, helping the tissue processing facility to predict the risk of suboptimal cell yield from a given cord tissue section and processing method, given different operating ranges. - Determining the tissue storage requirements and isolation method with acceptable risk of adequate cell recovery. - Characterization of cells extracted from UCT via different extraction methods and comparison to primary cells extracted from other tissue sources. - Investigation of cryopreservation method for UCT. The result of this work provides a solid example of the type of data and analysis that will be required to inform a Quality-by-Design type approach for cell product development and manufacture. It will help tissue processing facilities and banks to predict the probability of cell yields from tissue sections given different operating ranges, and to aid and inform the experimental approach of others.

Os protetores solares (PS) são os grandes responsáveis pela proteção da pele quando exposta à radiação solar, por isso a importância sanitária de se otimizar o desenvolvimento deste cosmético tipo II e monitorar para que seja eficaz em seu propósito. O principal objetivo deste trabalho é aplicar os conceitos de Qualidade por Design (QbD), ferramentas estatísticas de desenho experimental (DoE - Design of Experiments) e o conceito de tecnologia analítica de processo (PAT - Process Analytical Technology) para desenvolver uma formulação e processo produtivo de um PS de modo a modernizar os processos da indústria cosmética, fazendo as análises durante o processo e eliminando o controle de qualidade final. Trata-se de um sistema de desenvolvimento sistematizado, onde se executa as ferramentas de QbD para avaliar os dados obtidos ao longo da fase experimental. Para a fase experimental, empregou-se o desenho fatorial e desenho do compósito central (CCD - Central Composite Design) como ferramenta estatística, para a execução do planejamento de experimentos (DoE - Design of Experiments). As respostas foram analisadas através da metodologia de superfície resposta (RSM - Response Surface Methodology). Tais ferramentas são fundamentais para a determinação do desenho de concepção (design space), para se obter o PS com as melhores características físico-químicas e de processo dentro do escopo delineado. Para o desenvolvimento da metodologia de análise in line, optou-se pela utilização da espectrometria UV, utilizando-se ferramentas como análise de regressão dos mínimos quadrados (PLS) devido a praticidade em transforma-la em uma ferramenta PAT, para isto, a quimiometria foi empregada para modelar sistemas que são desconhecidos e complexos, como um PS, e trazendo respostas diretas como a aprovação do produto antes de ser embalado, por exemplo. A abordagem apresentada baseia-se na construção da qualidade ao longo do desenvolvimento e otimização de PS e torna possível o monitoramento da qualidade em tempo real. / The sunscreens are great responsible for the skin protection when it is exposed to direct sunlight, so it means a great importance of health to optimize the development of type II cosmetic and monitor for it to be effective in its purpose. The objective of this work is to apply the concepts of Quality by Design and statistical tools of experimental design (DoE - Design of experiments), as well as applying the process analytical technology (PAT - Process Analytical Technology) concept for formulation and manufacturing process development of a topical sunscreen being able to modernize the cosmetic industry processing, including real time analyses and eliminating quarantine step, which waits analysis approval performed by the quality assurance, and then release the product for sale. As it is a systematic development, where critical quality attributes and risk assessment were performed to evaluate over obtained data. During experimental phase, the factorial design was used as a statistical tool for design of experiments implementation, and the responses were analyzed by response surface methodology (RSM - Response Surface Methodology). This mapping is critical to determination of the product design (design space), i.e. get sunscreen with the best physical and chemical characteristics and processing within the outlined scope. For in line methodology development, UV spectrometry was opted to be used due to less effort in sample preparation and due to great easiness to turn it into a PAT tool. For this, chemometrics was used, which brings together chemical and statistical elements to obtain three main elements: empirical modeling, multivariate modeling and chemical data, making it able to model systems that are unknown and complex, as a sunscreen, getting direct answers as product release approval before being packed, for example. The presented approach was based on the construction of quality throughout the sunscreen development and optimization making possible the real time quality monitoring.

<div>Drug solubility is a persistent challenge in pharmaceutical product development. The objective of this research is to develop a formulation/processing strategy by means of a biodendrimeric solid dispersion (BDSD) platform, for increasing the solubility and dissolution rate of poorly water-soluble drugs. The BSDS platform combines a novel type of excipient, referred to as DLB, with a new application of the hot melt extrusion (HME) process.</div><div><br></div><div>Four model compounds – phenytoin (PHT), griseofulvin (GSF), ibuprofen (IBU), and loratadine (LOR) – were used to evaluate the solubilization effect of an octenylsuccinate-modified dendrimer-like biopolymer (OS-DLB). Shake-flask solubility measurements show that OS-DLB exerts significant solubilizing effect when present at less than 0.2% in water. The presence of hydrophobic C₈ chains on OS-DLB creates the type of favorable nonpolar microenvironment necessary for producing a parallel liquid phase equilibrium responsible for the increase in the total amount of drug dissolved in aqueous media. The higher the hydrophobicity of the drug, the higher the observed solubilization effect. Isothermal titration calorimetry studies show that drug solubilization by OS-DLB occurs by means of entropy-driven interactions. These studies also show that the intermolecular interaction between IBU and OS-DLB in solution exhibits very small energy change upon mixing but a stronger effect on entropy. In comparison, the intermolecular interaction between the less hydrophobic GSF and OS-DLB have significant effects on both enthalpy and entropy. Consequently, in terms of solubilization enhancement, it was found that the interaction between IBU and OS-DLB is entropy-driven (more favorable), while in the case of GSF, the interacting molecules are arranged to maximize enthalpic interaction.</div><div><br></div><div>Based on the solubility studies, a formulation/processing approach for enhancing the dissolution rate of the model drugs was developed. The biopolymer serving as both carrier and solubilizing agent, was coprocessed with poloxamer, functioning as a processing aid, using hot melt extrusion (HME) as an enabling technology. The result is a non-amorphous solid dispersion, exhibiting high and long-lasting supersaturation upon dissolution. A 3-factor, 3-level Box-Behnken design was implemented to define the optimal design space for the formulation/extrusion process. The results obtained from multivariate data analysis (partial least squares and principal components analysis) and response surface modeling suggest that drug release performance of IBU BDSDs is strongly influenced by the processing variables, while maximum release of GSF from the BDSDs can be attained through selective combination of functional excipients.<br></div>