970 resultados para functionality


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Durante as ultimas décadas, os registos de saúde eletrónicos (EHR) têm evoluído para se adaptar a novos requisitos. O cidadão tem-se envolvido cada vez mais na prestação dos cuidados médicos, sendo mais pró ativo e desejando potenciar a utilização do seu registo. A mobilidade do cidadão trouxe mais desafios, a existência de dados dispersos, heterogeneidade de sistemas e formatos e grande dificuldade de partilha e comunicação entre os prestadores de serviços. Para responder a estes requisitos, diversas soluções apareceram, maioritariamente baseadas em acordos entre instituições, regiões e países. Estas abordagens são usualmente assentes em cenários federativos muito complexos e fora do controlo do paciente. Abordagens mais recentes, como os registos pessoais de saúde (PHR), permitem o controlo do paciente, mas levantam duvidas da integridade clinica da informação aos profissionais clínicos. Neste cenário os dados saem de redes e sistemas controlados, aumentando o risco de segurança da informação. Assim sendo, são necessárias novas soluções que permitam uma colaboração confiável entre os diversos atores e sistemas. Esta tese apresenta uma solução que permite a colaboração aberta e segura entre todos os atores envolvidos nos cuidados de saúde. Baseia-se numa arquitetura orientada ao serviço, que lida com a informação clínica usando o conceito de envelope fechado. Foi modelada recorrendo aos princípios de funcionalidade e privilégios mínimos, com o propósito de fornecer proteção dos dados durante a transmissão, processamento e armazenamento. O controlo de acesso _e estabelecido por políticas definidas pelo paciente. Cartões de identificação eletrónicos, ou certificados similares são utilizados para a autenticação, permitindo uma inscrição automática. Todos os componentes requerem autenticação mútua e fazem uso de algoritmos de cifragem para garantir a privacidade dos dados. Apresenta-se também um modelo de ameaça para a arquitetura, por forma a analisar se as ameaças possíveis foram mitigadas ou se são necessários mais refinamentos. A solução proposta resolve o problema da mobilidade do paciente e a dispersão de dados, capacitando o cidadão a gerir e a colaborar na criação e manutenção da sua informação de saúde. A arquitetura permite uma colaboração aberta e segura, possibilitando que o paciente tenha registos mais ricos, atualizados e permitindo o surgimento de novas formas de criar e usar informação clínica ou complementar.

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Both skeletal and cardiac muscles daily burn tremendous amounts of ATP to meet the energy requirements for contraction. So, it is not surprising that the maintenance of mitochondrial morphology, number, distribution and functionality in striated muscle are important for muscle homeostasis. In these tissues mitochondria present the added dimension of two populations, the intermyofibrillar (IMF) and the subsarcolemmal (SS) mitochondria, being IMF the most abundant one. In the present thesis, the molecular mechanisms harboured in mitochondria of striated muscles were studied using animal models, to better comprehend the role of mitochondrial plasticity in several pathophysiological conditions such as aging, diabetes mellitus and bladder cancer. The comparative analysis of IMF and SS populations isolated from heart evidenced a higher respiratory chain activity of mitochondria interspersed in the contractile apparatus. The higher susceptible of SS respiratory chain complexes subunits to carbonylation, but not to nitration, seems to justify the lower respiratory chain activity observed in this mitochondrial population. Our results showed that in heart from aged mice there is an accumulation of dysfunctional mitochondria. The age-related decrease of oxidative phosphorylation activity seems to be justified, at least partially, by the increased proneness of mitochondrial proteins as OXPHOS subunits and MnSOD to oxidative modifications. Moreover, a sedentary lifestyle seems to worsen the functional consequences of aging in heart by increasing mitochondrial proteins susceptibility to nitration. In skeletal muscle from rats with type 1 diabetes mellitus induced by streptozotocin administration, we verified the accumulation of dysfunctional mitochondria due, at least in part, to the impairment of PQC system. Indeed, the decreased activity of AAA proteases was accompanied by the accumulation of oxidatively modified mitochondrial proteins with impact in respiratory chain activity. The diminishing of mitochondria activity also underlies cancer-induced muscle wasting. Indeed, using a rat model of chemically induced urothelial carcinoma we verified that the loss of gastrocnemius mass was related to mitochondrial dysfunction due to, at least partially, the down-regulation of PQC system involving the mitochondrial proteases paraplegin and Lon. PQC impairment resulted in the accumulation of oxidatively modified mitochondrial proteins. In overall, regardless the pathophysiological stimuli that promote mitochondrial alterations, there are similarities in the pattern of disease-related mitochondrial plasticity. The diminished capacity for ATP production in striated muscle seems to be due to increased oxidative damage of mitochondrial proteins, namely subunits of respiratory chain complexes, metabolic proteins and MnSOD. Our data highlighted, for the first time, the impact of mitochondrial PQC system impairment in the accumulation of oxidized proteins, exacerbating the dysfunction of this organelle in striated muscle in several pathophysiological conditions.

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The main motivation for the work presented here began with previously conducted experiments with a programming concept at the time named "Macro". These experiments led to the conviction that it would be possible to build a system of engine control from scratch, which could eliminate many of the current problems of engine management systems in a direct and intrinsic way. It was also hoped that it would minimize the full range of software and hardware needed to make a final and fully functional system. Initially, this paper proposes to make a comprehensive survey of the state of the art in the specific area of software and corresponding hardware of automotive tools and automotive ECUs. Problems arising from such software will be identified, and it will be clear that practically all of these problems stem directly or indirectly from the fact that we continue to make comprehensive use of extremely long and complex "tool chains". Similarly, in the hardware, it will be argued that the problems stem from the extreme complexity and inter-dependency inside processor architectures. The conclusions are presented through an extensive list of "pitfalls" which will be thoroughly enumerated, identified and characterized. Solutions will also be proposed for the various current issues and for the implementation of these same solutions. All this final work will be part of a "proof-of-concept" system called "ECU2010". The central element of this system is the before mentioned "Macro" concept, which is an graphical block representing one of many operations required in a automotive system having arithmetic, logic, filtering, integration, multiplexing functions among others. The end result of the proposed work is a single tool, fully integrated, enabling the development and management of the entire system in one simple visual interface. Part of the presented result relies on a hardware platform fully adapted to the software, as well as enabling high flexibility and scalability in addition to using exactly the same technology for ECU, data logger and peripherals alike. Current systems rely on a mostly evolutionary path, only allowing online calibration of parameters, but never the online alteration of their own automotive functionality algorithms. By contrast, the system developed and described in this thesis had the advantage of following a "clean-slate" approach, whereby everything could be rethought globally. In the end, out of all the system characteristics, "LIVE-Prototyping" is the most relevant feature, allowing the adjustment of automotive algorithms (eg. Injection, ignition, lambda control, etc.) 100% online, keeping the engine constantly working, without ever having to stop or reboot to make such changes. This consequently eliminates any "turnaround delay" typically present in current automotive systems, thereby enhancing the efficiency and handling of such systems.

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Dissertação de Mestrado , Ciências Económicas e Empresariais, Faculdade de Economia, Universidade do Algarve, 2008

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Dissertação mest., Gestão da água e da costa, Universidade do Algarve, 2007

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Induced pluripotent stem cells (iPSc) have great potential for applications in regenerative medicine, disease modeling and basic research. Several methods have been developed for their derivation. The original method of Takahashi and Yamanaka involved the use of retroviral vectors which result in insertional mutagenesis, presence in the genome of potential oncogenes and effects of residual transgene expression on differentiation bias of each particular iPSc line. Other methods have been developed, using different viral vectors (adenovirus and Sendai virus), transient plasmid transfection, mRNA transduction, protein transduction and use of small molecules. However, these methods suffer from low efficiencies; can be extremely labor intensive, or both. An additional method makes use of the piggybac transposon, which has the advantage of inserting its payload into the host genome and being perfectly excised upon re-expression of the transposon transposase. Briefly, a policistronic cassette expressing Oct4, Sox2, Klf4 and C-Myc flanked by piggybac terminal repeats is delivered to the cells along with a plasmid transiently expressing piggybac transposase. Once reprogramming occurs, the cells are re-transfected with transposase and subclones free of tranposon integrations screened for. The procedure is therefore very labor intensive, requiring multiple manipulations and successive rounds of cloning and screening. The original method for reprogramming with the the PiggyBac transposon was created by Woltjen et al in 2009 (schematized here) and describes a process with which it is possible to obtain insert-free iPSc. Insert-free iPSc enables the establishment of better cellular models of iPS and adds a new level of security to the use of these cells in regenerative medicine. Due to the fact that it was based on several low efficiency steps, the overall efficiency of the method is very low (<1%). Moreover, the stochastic transfection, integration, excision and the inexistence of an active way of selection leaves this method in need of extensive characterization and screening of the final clones. In this work we aime to develop a non-integrative iPSc derivation system in which integration and excision of the transgenes can be controlled by simple media manipulations, avoiding labor intensive and potentially mutagenic procedures. To reach our goal we developed a two vector system which is simultaneously delivered to original population of fibroblasts. The first vector, Remo I, carries the reprogramming cassette and GFP under the regulation of a constitutive promoter (CAG). The second vector, Eneas, carries the piggybac transposase associated with an estrogen receptor fragment (ERT2), regulated in a TET-OFF fashion, and its equivalent reverse trans-activator associated with a positive-negative selection cassette under a constitutive promoter. We tested its functionality in HEK 293T cells. The protocol is divided in two the following steps: 1) Obtaining acceptable transfection efficiency into human fibroblasts. 2) Testing the functionality of the construct 3) Determining the ideal concentration of DOX for repressing mPB-ERT2 expression 4) Determining the ideal concentration of TM for transposition into the genome 5) Determining the ideal Windows of no DOX/TM pulse for transposition into the genome 6) 3, 4 and 5) for transposition out of the genome 7) Determination of the ideal concentration of GCV for negative selection We successfully demonstrated that ENEAS behaved as expected in terms of DOX regulation of the expression of mPB-ERT2. We also demonstrated that by delivering the plasmid into 293T HEK cells and manipulating the levels of DOX and TM in the medium, we could obtain puromycin resistant lines. The number of puromycin resistant colonies obtained was significantly higher when DOX as absent, suggesting that the colonies resulted from transposition events. Presence of TM added an extra layer of regulation, albeit weaker. Our PCR analysis, while not a clean as would be desired, suggested that transposition was indeed occurring, although a background level of random integration could not be ruled out. Finally, our attempt to determine whether we could use GVC to select clones that had successfully mobilized PB out of the genome was unsuccessful. Unexpectedly, 293T HEK cells that had been transfected with ENEAS and selected for puromycin resistance were insensitive to GCV.

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Bone morphogenetic proteins (BMPs) are multifunctional growth factors belonging to the transforming growth factor β (TGFβ) superfamily with a central role in bone formation and mineralization. BMP2, a founding member of this family, has demonstrated remarkable osteogenic properties and is clinically used to promote bone repair and fracture healing. Lack of basic data on factors regulating BMP2 expression and activity have hampered a better understanding of its role in bone formation and bone-related diseases. The objective of this work was to collect new functional data and determine spatiotemporal expression patterns in a fish system aiming towards a better understanding of BMP2 function and regulation. Transcriptional and post-transcriptional regulation of gilthead seabream BMP2 gene was inferred from luciferase reporter systems. Several bone- and cartilage-related transcription factors (e.g. RUNX3, MEF2c, SOX9 and ETS1) were found to regulate BMP2 transcription, while microRNA 20a was shown to affect stability of the BMP2 transcript and thus the mineralogenic capacity of fish bone-derived host cells. The regulation of BMP2 activity through an interaction with the matrix Gla protein (MGP) was investigated in vitro using BMP responsive elements (BRE) coupled to luciferase reporter gene. Although we demonstrated the functionality of the experimental system in a fish cell line and the activation of BMP signaling pathway by seabream BMP2, no conclusive evidence could be collected on a possible interaction beween MGP and BMP2. The evolutionary relationship among the members of BMP2/4/16 subfamily was inferred from taxonomic and phylogenetic analyses. BMP16 diverged prior to BMP2 and BMP4 and should be the result of an ancient genome duplication that occurred early in vertebrate evolution. Structural and functional data suggested that all three proteins are effectors of the BMP signaling pathway, but expression data revealed different spatiotemporal patterns in teleost fish suggesting distinct mechanisms of regulation. In this work, through the collection of novel data, we provide additional insight into the regulation, the structure and the phylogenetic relationship of BMP2 and its closely related family members.

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Nowadays the importance of websites to the tourism and hospitality industries is fundamental. Hotels, for instance, spend a huge amount of money improving their websites to show all the activities and amenities that they can provide. There are studies to evaluate website performance based on functionality, usability and other factors; nevertheless, they are not exhaustive. This paper presents a framework for the characterization of hotel and resort websites, that was applied as a case study to the websites of 5-star hotels and resorts that operate in the tourism region of the Algarve, Portugal. This framework allows us to identify a set of features for the hotel and resort websites characterization. From these features, we propose a set of comprehensive indicators, grouping them into ten fundamental information dimensions, as well as the application of these indicators and information dimensions, which allows obtaining quantitative and qualitative results.

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The SmartVision prototype is a small, cheap and easily wearable navigation aid for blind and visually impaired persons. Its functionality addresses global navigation for guiding the user to some destiny, and local navigation for negotiating paths, sidewalks and corridors, with avoidance of static as well as moving obstacles. Local navigation applies to both in- and outdoor situations. In this article we focus on local navigation: the detection of path borders and obstacles in front of the user and just beyond the reach of the white cane, such that the user can be assisted in centering on the path and alerted to looming hazards. Using a stereo camera worn at chest height, a portable computer in a shoulder-strapped pouch or pocket and only one earphone or small speaker, the system is inconspicuous, it is no hindrence while walking with the cane, and it does not block normal surround sounds. The vision algorithms are optimised such that the system can work at a few frames per second.

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[Updated August 2016] The Hotel Valuation Software, freely available from Cornell’s Center for Hospitality Research, has been updated to reflect the many changes in the 11th Edition of the Uniform System of Accounts for the Lodging Industry (USALI). Version 4.0 of the Hotel Valuation Software provides numerous enhancements over the original tool from 2011. In addition to a significant increase in functionality and an update to reflect the 11th edition of the USALI, Version 4.0 takes advantage of the power of the latest release of Microsoft Excel®. Note that Version 4.0 works only on a PC running Microsoft Windows, it does not work on a Mac running OS X. Users desiring an OS X compatible version should click here (Labeled as Version 2.5). 酒店评估软件手册和三个程序(点击这里 ) Users desiring a Mandarin version of the Hotel Valuation Software should click here The Hotel Valuation Software remains the only non-proprietary computer software designed specifically to assist in the preparation of market studies, forecasts of income and expense, and valuations for lodging property. The software provides an accurate, consistent, and cost-effective way for hospitality professionals to forecast occupancy, revenues and expenses and to perform hotel valuations. Version 4.0 of the Hotel Valuation Software includes the following upgrades – a complete update to reflect the 11th edition of the USALI – the most significant change to the chart of accounts in a generation, an average daily rate forecasting tool, a much more sophisticated valuation module, and an optional valuation tool useful in periods of limited capital liquidity. Using established methodology, the Hotel Valuation Software is a sophisticated tool for lodging professionals. The tool consists of three separate software programs written as Microsoft Excel files and a software users' guide. The tool is provided through the generosity of HVS and the School of Hotel Administration. The three software modules are: Room Night Analysis and Average Daily Rate: Enables the analyst to evaluate the various competitive factors such as occupancy, average room rate, and market segmentation for competitive hotels in a local market. Calculates the area-wide occupancy and average room rate, as well as the competitive market mix. Produce a forecast of occupancy and average daily rate for existing and proposed hotels in a local market. The program incorporates such factors as competitive occupancies, market segmentation, unaccommodated demand, latent demand, growth of demand, and the relative competitiveness of each property in the local market. The program outputs include ten-year projections of occupancy and average daily rate. Fixed and Variable Revenue and Expense Analysis: The key to any market study and valuation is a supportable forecast of revenues and expenses. Hotel revenue and expenses are comprised of many different components that display certain fixed and variable relationships to each other. This program enables the analyst to input comparable financial operating data and forecast a complete 11-year income and expense statement by defining a small set of inputs: The expected future occupancy levels for the subject hotel Base year operating data for the subject hotel Fixed and variable relationships for revenues and expenses Expected inflation rates for revenues and expenses Hotel Capitalization Software: A discounted cash flow valuation model utilizing the mortgage-equity technique forms the basis for this program. Values are produced using three distinct underwriting criteria: A loan-to-value ratio, in which the size of the mortgage is based on property value. A debt coverage ratio (also known as a debt-service coverage ratio), in which the size of the mortgage is based on property level cash flow, mortgage interest rate, and mortgage amortization. A debt yield, in which the size of the mortgage is based on property level cash flow. By entering the terms of typical lodging financing, along with a forecast of revenue and expense, the program determines the value that provides the stated returns to the mortgage and equity components. The program allows for a variable holding period from four to ten years The program includes an optional model useful during periods of capital market illiquidity that assumes a property refinancing during the holding period

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The October 2015 Food and Beverage Entrepreneurship Roundtable brought together over 30 food and beverage industry leaders, entrepreneurs, faculty, and students at the School of Hotel Administration at Cornell University. Discussion topics covered entrepreneurship in the food and beverage industry, including development, intrapreneurship, operational efficiency, beverage product development, and technology. The roundtable began with the presentation of a five-point framework on food and beverage venue development. The first three phases focused on the launch of a venue, including how to define the guest experience; the creation of operational functionality by strategically planning out the design, flow, and efficiency of a defined space; and development capacity. The remaining two points of the framework focused on post-opening considerations, including operating systems and culture development. Participants discussed the importance of culture in the growth of a business. They suggested that intrapreneurship needs to be fostered in the culture of an organization and in an educational curriculum for those who are preparing to enter the industry. Participants also discussed the fine balance between setting expectations for an experience and subsequently being able to maintain this experience in a fast changing environment. In particular they considered what it means to say no to customers. A discussion on the beverage industry focused on how to distribute products in a crowded marketplace. One method to ensure that the product gets into the hands of the consumers is face-to-face sales. Finally, in the technology session, the group discussed technology adoption, specifically focusing on the point at which technology detracts from the guest experience, how to minimize operational risk from technology, and how to maximize consumers’ adoption rates.

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Tese de doutoramento, Farmácia (Biologia Celular e Molecular), Universidade de Lisboa, Faculdade de Farmácia, 2014

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Tese de doutoramento, Farmácia (Química Farmacêutica e Terapêutica), Universidade de Lisboa, Faculdade de Farmácia, 2014

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Tese de doutoramento, Farmácia (Química Farmacêutica e Terapêutica), Universidade de Lisboa, Faculdade de Farmácia, 2014

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Tese de doutoramento, Educação (História da Educação), Universidade de Lisboa, Instituto de Educação, 2015