Design of an intravaginal ring for the controlled delivery of 17b-estradiol as its 3-acetate ester

Suitable ester prodrugs of 17b-estradiol are identified, thus permitting effective sustained and controlled estrogen replacement therapy (ERT) from an elastomeric, silicone intravaginal ring (IVR). IVR devices of reservoir design were prepared by blending silicone elastomer base with n-propylorthosilicate (cross-linker) and 10% w/w of 17b-estradiol or an ester prodrug, the mix being activated with 0.5% w/w stannous octoate and cured at 808C for 2 min. A rate-controlling membrane was similarly prepared, without the active agent. IVR devices were of cross-sectional diameter 9 mm, outer diameter 54 mm, with core cross-sectional diameter of 2 mm and core length varied as required. Sink conditions were evident for the 17b-estradiol esters in 1.0% aqueous benzalkonium chloride solution. The low release rates into 0.9% w/v saline of the lipophilic valerate and benzoate esters were due to their intrinsically low aqueous solubilities. In vivo, these esters failed to raise plasma estradiol above baseline levels in postmenopausal human volunteers, despite good in vitro release characteristics under sink conditions. The best release rates under sink conditions, in combination with substantial aqueous solubilities as indicated by the release rates into saline, were observed for the acetate and propionate esters. A
combination of drug release characteristics, short plasma half-life and a toxicologically acceptable hydrolysis product indicated that 17b-estradiol-3-acetate was the prodrug of choice for IVR delivery of ERT. In vivo, an IVR device releasing
100 mg/day of estradiol as its 3-acetate ester maintained over 84 days a circulating plasma concentration in the region of 300 pmol l , within the clinically desirable range for ERT.

A new performance based method for design and maintenance of reinforced concrete structures

Best concrete research paper by a student - Research has shown that the cost of managing structures puts high strain on the infrastructure budget, with
estimates of over 50% of the European construction budget being dedicated to repair and maintenance. If reinforced concrete
structures are not suitably designed and adequately maintained, their service life is compromised, resulting in the full economic
value of the investment not realised. The issue is more prevalent in coastal structures as a result of combinations of aggressive
actions, such as those caused by chlorides, sulphates and cyclic freezing and thawing.
It is a common practice nowadays to ensure durability of reinforced concrete structures by specifying a concrete mix and a
nominal cover at the design stage to cater for the exposure environment. This in theory should produce the performance required
to achieve a specified service life. Although the European Standard EN 206-1 specifies variations in the exposure environment,
it does not take into account the macro and micro climates surrounding structures, which have a significant influence on their
performance and service life. Therefore, in order to construct structures which will perform satisfactorily in different exposure
environments, the following two aspects need to be developed: a performance based specification to supplement EN 206-1
which will outline the expected performance of the structure in a given environment; and a simple yet transferrable procedure
for assessing the performance of structures in service termed KPI Theory. This will allow the asset managers not only to design
structures for the intended service life, but also to take informed maintenance decisions should the performance in service fall
short of what was specified. This paper aims to discuss this further.

Assembly Design and Evaluation in an Augmented Reality Environment

The technologies and methodologies of assembly design and evaluation in the early design stage are highly significant to product development. This paper looks at a promising technology to mix real components (e.g. physical prototypes, assembly tools, machines, etc.) with virtual components to create an Augmented Reality (AR) interface for assembly process evaluation. The goal of this paper is to clarify the methodologies and enabling technologies of how to establish an AR assembly simulation and evaluation environment. The architecture of an AR assembly system is proposed and the important functional modules including AR environment set-up, design for assembly (DFA) analysis and AR assembly sequence planning in an AR environment are discussed in detail.

Archives information publishing new design in post-custodial regime: The National Archives Experience Digital Vaults

The uses of Information and Communication Technologies (ICT) and Web environments for creation, treatment and availability of information have supported the emergence of new social-cultural patterns represented by convergences in textual, image and audio languages. This paper describes and analyzes the National Archives Experience Digital Vaults as a digital publishing web environment and as a cultural heritage. It is a complex system - synthesizer of information design options at information setting, provides new aesthetic aspects, but specially enlarges the cognition of the subjects who interact with the environment. It also enlarges the institutional spaces that guard the collective memory beyond its role of keeping the physical patrimony collected there. Digital Vaults lies as a mix of guide and interactive catalogue to be dealt in a ludic way. The publishing design of the information held on the Archives is meant to facilitate access to knowledge. The documents are organized in a dynamic and not chronological way. They are not divided in fonds or distinct categories, but in controlled interaction of documents previously indexed and linked by the software. The software creates information design and view of documental content that can be considered a new paradigm in Information Science and are part of post-custodial regime, independent from physical spaces and institutions. Information professionals must be prepared to understand and work with the paradigmatic changes described and represented by the new hybrid digital environments; hence the importance of this paper. Cyberspace interactivity between user and the content provided by the environment design provide cooperation, collaboration and sharing knowledge actions, all features of networks, transforming culture globally. © 2011 - IOS Press and the authors. All rights reserved.

Archives information publishing new design in post-custodial regime: The National Archives Experience Digital Vaults

The uses of Information and Communication Technologies (ICT) and Web environments for creation, treatment and availability of information have supported the emergence of new social-cultural patterns represented by convergences in textual, image and audio languages. This paper describes and analyzes the National Archives Experience Digital Vaults as a digital publishing web environment and as a cultural heritage. It is a complex system - synthesizer of information design options at information setting, provides new aesthetic aspects, but specially enlarges the cognition of the subjects who interact with the environment. It also enlarges the institutional spaces that guard the collective memory beyond its role of keeping the physical patrimony collected there. Digital Vaults lies as a mix of guide and interactive catalogue to be dealt in a ludic way. The publishing design of the information held on the Archives is meant to facilitate access to knowledge. The documents are organized in a dynamic and not chronological way. They are not divided in fonds or distinct categories, but in controlled interaction of documents previously indexed and linked by the software. The software creates information design and view of documental content that can be considered a new paradigm in Information Science and are part of post-custodial regime, independent from physical spaces and institutions. Information professionals must be prepared to understand and work with the paradigmatic changes described and represented by the new hybrid digital environments; hence the importance of this paper. Cyberspace interactivity between user and the content provided by the environment design provide cooperation, collaboration and sharing knowledge actions, all features of networks, transforming culture globally.

Avaliação do efeito da combinação de pectina, gelatina e alginato de sódio sobre as características de gel de fruta estruturada a partir de "mix" de polpa de cajá e mamão, por meio da metodologia de superfície de resposta

Este trabalho teve por objetivo estabelecer procedimento tecnológico para produção de fruta estruturada a partir de "mix" de polpa de cajá e mamão, procurando unir as propriedades sensoriais de cada uma das frutas e potencializar as características funcionais do produto final. Avaliou-se o efeito da combinação de pectina, gelatina e alginato de sódio, via metodologia de superfície de resposta, nas características do gel de fruta. As polpas de mamão e cajá e os estruturados obtidos foram caracterizados com relação aos compostos funcionais, avaliando-se o teor de taninos e carotenóides totais, além das análises de composição centesimal, pH, acidez titulável, sólidos solúveis, açúcares, atividade de água, carboidratos e valor energético total. Os resultados obtidos através do planejamento experimental indicam que para o estruturado misto de cajá e mamão, somente o aumento da concentração de gelatina afeta a firmeza do produto final. Os estruturados de frutas desenvolvidos apresentaram boa aceitação sensorial para todos os atributos avaliados. Com relação à intenção de compra, 70% dos provadores responderam que provavelmente ou certamente, comprariam o estruturado misto de cajá e mamão se o encontrassem à venda.

Produção de etanol utilizando mix de sorgo sacarino e cana-de-açúcar em processo de maturação

Pós-graduação em Microbiologia Agropecuária - FCAV

Archives information publishing new design in post-custodial regime: the national archives experience digital vaults

The uses of Information and Communication Technologies (ICT) and Web environments for creation, treatment and availability of information have supported the emergence of new social-cultural patterns represented by convergences in textual, image and audio languages. This paper describes and analyzes the National Archives Experience Digital Vaults as a digital publishing web environment and as a cultural heritage. It is a complex system - synthesizer of information design options at information setting, provides new aesthetic aspects, but specially enlarges the cognition of the subjects who interact with the environment. It also enlarges the institutional spaces that guard the collective memory beyond its role of keeping the physical patrimony collected there. Digital Vaults lies as a mix of guide and interactive catalogue to be dealt in a ludic way. The publishing design of the information held on the Archives is meant to facilitate access to knowledge. The documents are organized in a dynamic and not chronological way. They are not divided in fonds or distinct categories, but in controlled interaction of documents previously indexed and linked by the software. The software creates information design and view of documental content that can be considered a new paradigm in Information Science and are part of post-custodial regime, independent from physical spaces and institutions. Information professionals must be prepared to understand and work with the paradigmatic changes described and represented by the new hybrid digital environments; hence the importance of this paper. Cyberspace interactivity between user and the content provided by the environment design provide cooperation, collaboration and sharing knowledge actions, all features of networks, transforming culture globally.

Newer optics efficiently mix, dim, and color-tune LED light

Low-cost, plastic-injected optics mix light from different color LED dies without a significant decrease in average brightness, simplifying luminaire design both optically and electronically. In solid-state lighting, high-flux and high-color rendering index (CRI) light engines may be achieved by arraying and mixing the light from different color dies or phosphors, or a combination of the two, in the LED package. However, these nonhomogeneous sources, when combined with luminaire optics, tend to produce patterns with undesirable artifacts such as spatial and angular nonuniformities and color separation.

Design of a new neutron delivery system for high flux source

La construcción en la actualidad de nuevas fuentes para el uso de haces de neutrones así como los programas de renovación en curso en algunas de las instalaciones experimentales existentes han evidenciado la necesidad urgente de desarrollar la tecnología empleada para la construcción de guías de neutrones con objeto de hacerlas mas eficientes y duraderas. Esto viene motivado por el hecho de que varias instalaciones de experimentación con haces de neutrones han reportado un número de incidentes mecánicos con tales guías, lo que hace urgente el progresar en nuestro conocimiento de los susbtratos vítreos sobre los cuales se depositan los espejos que permiten la reflexión total de los neutrones y como aquellos se degradan con la radiación. La presente tesis se inscribe en un acuerdo de colaboración establecido entre el Institut Max von Laue - Paul Langevin (ILL) de Grenoble y el Consorcio ESS-Bilbao con objeto de mejorar el rendimiento y sostenibilidad de los sistemas futuros de guiado de neutrones. El caso de la Fuente Europea de Espalación en construcción en Lund sirve como ejemplo ya que se contempla la instalación de guías de neutrones de más de 100 metros en algunos de los instrumentos. Por otro lado, instalaciones como el ILL prevén también dentro del programa Endurance de rejuvenecimiento la reconstrucción de varias líneas de transporte de haz. Para el presente estudio se seleccionaron cuatro tipos de vidrios borosilicatados que fueron el Borofloat, N-ZK7, N-BK7 y SBSL7. Los tres primeros son bien conocidos por los especialistas en instrumentación neutrónica ya que se han empleado en la construcción de varias instalaciones mientras que el último es un candidato potencial en la fabricación de substratos para espejos neutrónicos en un futuro. Los cuatro vidrios tiene un contenido en óxido de Boro muy similar, approximadamente un 10 mol.%. Tal hecho que obedece a las regulaciones para la fabricación de estos dispositivos hace que tales substratos operen como protección radiológica absorbiendo los neutrones transmitidos a través del espejo de neutrones. Como contrapartida a tal beneficio, la reacción de captura 10B(n,_)7Li puede degradar el substrato vítreo debido a los 2.5 MeV de energía cinética depositados por la partícula _ y los núcleos en retroceso y de hecho la fragilidad de tales vidrios bajo radiación ha sido atribuida desde hace ya tiempo a los efectos de esta reacción. La metodología empleada en esta tesis se ha centrado en el estudio de la estructura de estos vidrios borosilicatados y como esta se comporta bajo condiciones de radiación. Los materiales en cuestión presentan estructuras que dependen de su composición química y en particular del ratio entre formadores y modificadores de la red iono-covalente. Para ello se han empleado un conjunto de técnicas de caracterización tanto macro- como microscópicas tales como estudios de dureza, TEM, Raman, SANS etc. que se han empleado también para determinar el comportamiento de estos materiales bajo radiación. En particular, algunas propiedades macroscópicas relacionadas con la resistencia de estos vidrios como elementos estructurales de las guías de neutrones han sido estudiadas así como también los cambios en la estructura vítrea consecuencia de la radiación. Para este propósito se ha diseñado y fabricado por el ILL un aparato para irradiación de muestras con neutrones térmicos en el reactor del ILL que permite controlar la temperatura alcanzada por la muestra a menos de 100 °C. Tal equipo en comparación con otros ya existences permite en cuestión de dias acumular las dosis recibidas por una guía en operación a lo largo de varios años. El uso conjunto de varias técnicas de caracterización ha llevado a revelar que los vidrios aqui estudiados son significativamente diferentes en cuanto a su estructura y que tales diferencias afectan a sus propiedades macroscópicas asi como a su comportamiento bajo radiación. Tal resultado ha sido sorprendente ya que, como se ha mencionado antes, algunos de estos vidrios eran bien conocidos por los fabricantes de guías de neutrones y hasta el momento eran considerados prácticamente similares debido a su contenido comparable en óxido de Boro. Sin embargo, los materiales N-BK7 and S-BSL7 muetran gran homogeneidad a todas las escalas de longitud, y más específicamente, a escalas nanométricas las subredes de Sílice y óxido de Boro se mezclan dando logar a estructuras locales que recuerdan a la del cristal de Reedmergnerita. Por el contrario, N-ZK7 y Borofloat muestran dominios separados ricos en Sílice o Boro. Como era de esperar, las importantes diferencias arriba mencionadas se traducen en comportamientos dispares de estos materiales bajo un haz de neutrones térmicos. Los resultados muestran que el N-BK7 y el S-BSL7 son los más estables bajo radiación, lo que macroscópicamente hace que estos materiales muestren un comportamiento similar expandiéndose lentamente en función de la dosis recibida. Por el contario, los otros dos materiales muestran un comportamiento mucho más reactivo, que hace que inicialmente se compacten con la dosis recibida lo que hace que las redes de Silicio y Boro se mezclen resultando en un incremento en densidad hasta alcanzar un valor límite, seguido por un proceso de expansión lenta que resulta comparable al observado para N-BK7 y SBSL7. Estos resultados nos han permitido explicar el origen de las notorias diferencias observadas en cuanto a las dosis límite a partir de las cuales estos materiales desarrollan procesos de fragmentación en superficie. ABSTRACT The building of new experimental neutron beam facilities as well as the renewal programmes under development at some of the already existing installations have pinpointed the urgent need to develop the neutron guide technology in order to make such neutron transport devices more efficient and durable. In fact, a number of mechanical failures of neutron guides have been reported by several research centres. It is therefore important to understand the behaviour of the glass substrates on top of which the neutron optics mirrors are deposited and how these materials degrade under radiation conditions. The case of the European Spallation Source (ESS) at present under construction at Lund is a good example. It previews the deployment of neutron guides having more than 100 metres of length for most of the instruments. Also, the future renovation programme of the ILL, called Endurance, foresees the refurbishment of several beam lines. This Ph.D. thesis was the result of a collaboration agreement between the ILL and ESS-Bilbao aiming to improve the performance and sustainability of future neutron delivery systems. Four different industrially produced alkali-borosilicate glasses were selected for this study: Borofloat, N-ZK7, N-BK7 and SBSL7. The first three are well known within the neutron instrumentation community as they have already been used in several installations whereas the last one is at present considered as a candidate for making future mirror substrates. All four glasses have a comparable content of boron oxide of about 10 mol.%. The presence of such a strong neutron absorption element is in fact a mandatory component for the manufacturing of neutron guides because it provides a radiological shielding for the environment. This benefit is however somewhat counterbalanced since the resulting 10B(n,_)7Li reactions degrade the glass due to the deposited energy of 2.5 MeV by the _ particle and the recoil nuclei. In fact, the brittleness of some of these materials has been ascribed to this reaction. The methodology employed by this study consisted in understanding the general structure of borosilicates and how they behave under irradiation. Such materials have a microscopic structure strongly dependent upon their chemical content and particularly on the ratios between network formers and modifiers. The materials have been characterized by a suite of macroscopic and structural techniques such as hardness, TEM, Raman, SANS, etc. and their behaviour under irradiation was analysed. Some macroscopic properties related to their resistance when used as guide structural elements were monitored. Also, changes in the vitreous structure due to radiation were observed by means of several experimental tools. For such a purpose, an irradiation apparatus has been designed and manufactured to enable irradiation with thermal neutrons within the ILL reactor while keeping the samples below 100 °C. The main advantage of this equipment if compared to others previously available was that it allowed to reach in just some days an equivalent neutron dose to that accumulated by guides after several years of use. The concurrent use of complementary characterization techniques lead to the discovery that the studied glasses were deeply different in terms of their glass network. This had a strong impact on their macroscopic properties and their behaviour under irradiation. This result was a surprise since, as stated above, some of these materials were well known by the neutron guide manufacturers, and were considered to be almost equivalent because of their similar boron oxide content. The N-BK7 and S-BSL7 materials appear to be fairly homogeneous glasses at different length scales. More specifically, at nanometre scales, silicon and boron oxide units seem to mix and generate larger structures somewhat resembling crystalline Reedmergnerite. In contrast, N-ZK7 and Borofloat are characterized by either silicon or boron rich domains. As one could expect, these drastic differences lead to their behaviour under thermal neutron flux. The results show that N-BK7 and S-BSL7 are structurally the most stable under radiation. Macroscopically, such stability results in the fact that these two materials show very slow swelling as a function or radiation dose. In contrast, the two other glasses are much more reactive. The whole glass structure compacts upon radiation. Specifically, the silica network, and the boron units tend to blend leading to an increase in density up to some saturation, followed by a very slow expansion which comes to be of the same order than that shown by N-BK7 and S-BSL7. Such findings allowed us to explain the drastic differences in the radiation limits for macroscopic surface splintering for these materials when they are used in neutron guides.

An investigation of the retail marketing mix and its effectiveness in small shops

The recent history of small shop and independent retailing has been one of decline. The most desirable form of assistance is the provision of information which will increase the efficiency model of marketing mix effeciveness which may be applied in small scale retailing. A further aim is to enhance theoretical development in the marketing field. Recent changes in retailing have affected location, product range, pricing and promotion practices. Although a large number of variables representing aspects of the marketing mix may be identified, it is not possible, on the basis of currently available information, to quantify or rank them according to their effect on sales performance. In designing a suitable study a major issue is that of access to a suitable representative sample of small retailers. The publish nature of the retail activities involved facilitates the use of a novel observation approach to data collection. A cross-sectional survey research design was used focussing on a clustered random sample of greengrocers and gent's fashion outfitters in the West Midlands. Linear multiple regression was the main analytical technique. Powerful regression models were evolved for both types of retailing. For greengrocers the major influences on trade are pedestrian traffic and shelf display space. For gent's outfitters they are centrality-to-other shopping, advertising and shelf display space. The models may be utilised by retailers to determine the relative strength of marketing mix variables. The level of precision is not sufficient to permit cost benefit analysis. Comparison of the findings for the two distinct kinds of business studied suggests an overall model of marketing mix effectiveness might be based on frequency of purchase, homogeneity of the shopping environment, elasticity of demand and bulk characteristics of the good sold by a shop.

Design rationnel de nanothermomètres programmables à base d’ADN

Développer de nouveaux nanomatériaux, interrupteurs et machines nanométriques sensibles à de petites variations de température spécifiques devrait être de grande utilité pour une multitude de domaines œuvrant dans la nanotechnologie. De plus, l’objectif est de convaincre le lecteur que les nanotechnologies à base d’ADN offrent d’énormes possibilités pour la surveillance de température en temps réel à l’échelle nanométrique. Dans la section Résultats, nous exploitons les propriétés de l’ADN pour créer des thermomètres versatiles, robustes et faciles à employer. En utilisant une série de nouvelles stratégies inspirées par la nature, nous sommes en mesure de créer des nanothermomètres d’ADN capables de mesurer des températures de 25 à 95°C avec une précision de <0.1°C. En créant de nouveaux complexes d’ADN multimériques, nous arrivons à développer des thermomètres ultrasensibles pouvant augmenter leur fluorescence 20 fois sur un intervalle de 7°C. En combinant plusieurs brins d’ADN avec des plages dynamiques différentes, nous pouvons former des thermomètres montrant une transition de phase linéaire sur 50°C. Finalement, la vitesse de réponse et la précision des thermomètres développés et leur réversibilité sont illustrées à l’aide d’une expérience de surveillance de température à l’intérieur d’un unique puits d’un appareil de qPCR. En conclusion, les applications potentielles de tels nanothermomètres en biologie synthétique, imagerie thermique cellulaire, nanomachines d’ADN et livraison contrôlée seront considérées.

Design rationnel de nanothermomètres programmables à base d’ADN

Développer de nouveaux nanomatériaux, interrupteurs et machines nanométriques sensibles à de petites variations de température spécifiques devrait être de grande utilité pour une multitude de domaines œuvrant dans la nanotechnologie. De plus, l’objectif est de convaincre le lecteur que les nanotechnologies à base d’ADN offrent d’énormes possibilités pour la surveillance de température en temps réel à l’échelle nanométrique. Dans la section Résultats, nous exploitons les propriétés de l’ADN pour créer des thermomètres versatiles, robustes et faciles à employer. En utilisant une série de nouvelles stratégies inspirées par la nature, nous sommes en mesure de créer des nanothermomètres d’ADN capables de mesurer des températures de 25 à 95°C avec une précision de <0.1°C. En créant de nouveaux complexes d’ADN multimériques, nous arrivons à développer des thermomètres ultrasensibles pouvant augmenter leur fluorescence 20 fois sur un intervalle de 7°C. En combinant plusieurs brins d’ADN avec des plages dynamiques différentes, nous pouvons former des thermomètres montrant une transition de phase linéaire sur 50°C. Finalement, la vitesse de réponse et la précision des thermomètres développés et leur réversibilité sont illustrées à l’aide d’une expérience de surveillance de température à l’intérieur d’un unique puits d’un appareil de qPCR. En conclusion, les applications potentielles de tels nanothermomètres en biologie synthétique, imagerie thermique cellulaire, nanomachines d’ADN et livraison contrôlée seront considérées.

Policy mixes for resource efficiency – conceptual issues, design and assessment challenges

Since the 1950s the global consumption of natural resources has skyrocketed, both in magnitude and in the range of resources used. Closely coupled with emissions of greenhouse gases, land consumption, pollution of environmental media, and degradation of ecosystems, as well as with economic development, increasing resource use is a key issue to be addressed in order to keep the planet Earth in a safe and just operating space. This requires thinking about absolute reductions in resource use and associated environmental impacts, and, when put in the context of current re-focusing on economic growth at the European level, absolute decoupling, i.e., maintaining economic development while absolutely reducing resource use and associated environmental impacts. Changing behavioural, institutional and organisational structures that lock-in unsustainable resource use is, thus, a formidable challenge as existing world views, social practices, infrastructures, as well as power structures, make initiating change difficult. Hence, policy mixes are needed that will target different drivers in a systematic way. When designing policy mixes for decoupling, the effect of individual instruments on other drivers and on other instruments in a mix should be considered and potential negative effects be mitigated. This requires smart and time-dynamic policy packaging. This Special Issue investigates the following research questions: What is decoupling and how does it relate to resource efficiency and environmental policy? How can we develop and realize policy mixes for decoupling economic development from resource use and associated environmental impacts? And how can we do this in a systemic way, so that all relevant dimensions and linkages—including across economic and social issues, such as production, consumption, transport, growth and wellbeing­—are taken into account? In addressing these questions, the overarching goals of this Special Issue are to: address the challenges related to more sustainable resource-use; contribute to the development of successful policy tools and practices for sustainable development and resource efficiency (particularly through the exploration of socio-economic, scientific, and integrated aspects of sustainable development); and inform policy debates and policy-making. The Special Issue draws on findings from the EU and other countries to offer lessons of international relevance for policy mixes for more sustainable resource-use, with findings of interest to policy makers in central and local government and NGOs, decision makers in business, academics, researchers, and scientists.

Estratégias de conteúdo digital. O caso de um estágio na Nata Design

Dissertação de Mestrado, Marketing, Faculdade de Economia, Universidade do Algarve, 2016