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.

Integrating allowable design strains in composites with whole life value

Fibre-Reinforced Plastics (FRPs) have been used in civil aerospace vehicles for decades. The current state-of-the-art in airframe design and manufacture results in approximately half the airframe mass attributable to FRP materials. The continual increase in the use of FRP materials over metallic alloys is attributable to the material's superior specific strength and stiffness, fatigue performance and corrosion resistance. However, the full potential of these materials has yet to be exploited as analysis methods to predict physical failure with equal accuracy and robustness are not yet available. The result is a conservative approach to design, but one that can bring benefit via increased inspection intervals and reduced cost over the vehicle life. The challenge is that the methods used in practice are based on empirical tests and real relationships and drivers are difficult to see in this complex process and so the trade-off decision is challenging and uncertain. The aim of this feasibility study was to scope a viable process which could help develop some rules and relationships based on the fundamental mechanics of composite material and the economics of production and operation, which would enhance understanding of the role and impact of design allowables across the life of a composite structure.

Optimal design of long-span steel portal frames using fabricated beams

This paper considers the optimal design of fabricated steel beams for long-span portal frames. The design optimisation takes into account ultimate as well as serviceability limit states, adopting deflection limits recommended by the Steel Construction Institute (SCI). Results for three benchmark frames demonstrate the efficiency of the optimisation methodology. A genetic algorithm (GA) was used to optimise the dimensions of the plates used for the columns, rafters and haunches. Discrete decision variables were adopted for the thickness of the steel plates and continuous variables for the breadth and depth of the plates. Strategies were developed to enhance the performance of the GA including solution space reduction and a hybrid initial population half of which is derived using Latin hypercube sampling. The results show that the proposed GA-based optimisation model generates optimal and near-optimal solutions consistently. A parametric study is then conducted on frames of different spans. A significant variation in weight between fabricated and conventional hot-rolled steel portal frames is shown; for a 50 m span frame, a 14–19% saving in weight was achieved. Furthermore, since Universal Beam sections in the UK come from a discrete section library, the results could also provide overall dimensions of other beams that could be more efficient for portal frames. Eurocode 3 was used for illustrative purposes; any alternative code of practice may be used.

Design e avaliação de pictogramas farmacêuticos

A informação inerente aos medicamentos no processo de medicação e prescrição tem revelado insuficiências relativamente às necessidades do utilizador. Este projecto aborda essas dificuldades e procura contribuir, através do design e avaliação de pictogramas farmacêuticos, para um melhor acesso das pessoas à informação, oral e escrita, prestada por médicos, farmacêuticos e pela literatura inclusa dos medicamentos. Verificámos que, nos últimos 40 anos, se desenvolveram quase mil representações gráficas, provenientes de 20 países, sobre mensagens relativas a perigos, precauções e informações de como tomar o medicamento. Com base nesse conjunto mundial colectado, tão alargado e diversificado, procedeu-se à analise, agrupamento e comparação dessas representações com vista a apurar a diversidade gráfica e escrita das 75 mensagens farmacêuticas identificadas nesta investigação. Foi seguidamente consultada uma centena de profissionais de saúde dentro da área farmacêutica para selecção e definição da informação a ser projectada em pictogramas. Algumas das mensagens seleccionadas foram, por ordem de importância: “Não aplicar nos olhos”, “Não beber álcool enquanto estiver a tomar o medicamento” e “Guardar no frigorífico”. Foi concebido um sistema PictoPharma, bilingue (Português e Inglês), composto por 32 pictogramas farmacêuticos, com várias possibilidades cromáticas de acordo com as diversas aplicações para suportes de impressão e ecrã (Registo de Propriedade Industrial – marca e design). Embora o sistema projectado possa aumentar a capacidade de recordar as informações importantes pelas pessoas em geral, os públicos-alvo que mais beneficiarão com o sistema são: pessoas que apresentam especiais dificuldades de leitura - analfabetos, pessoas com nenhum conhecimento ou um conhecimento limitado da língua; pessoas com dificuldades para relembrar e / ou compreender o tratamento - população envelhecida, sob múltiplos tratamentos ou com menores capacidades intelectuais; pessoas que não falam a língua local ou são de uma cultura diferente - estrangeiros, turistas, imigrantes. Foram feitos testes de usabilidade com os públicos-alvo específicos, de forma a verificar a percentagem de compreensão dos pictogramas, sem a respectiva legenda e de acordo com as normas internacionais de normalização. Os resultados dos testes indicaram que metade do sistema atingiu os 100% de compreensão e a outra metade atingiu mais de 88%. O sistema PictoPharma criado caracteriza-se: pelo design gráfico no seu contraste visual e na possibilidade de leitura numa escala reduzida; pelo conceito de familiaridade gráfica representada no seu conjunto, de forma a tornar os pictogramas mais facilmente memorizáveis; pelo estudo feito para minimizar especificidades culturais visuais; pelas diversas aplicações possíveis na indústria; pelas direcções que aponta para futuras investigações sobre as escolhas visuais culturais inerentes a um projecto de design com este.

The role of guarantees in pension plan design: Pension saving decisions

This study centers on the assessment of psychological value of guarantees in pension products and the behavior biases associated with choice. When a guarantee on a product increases from 99% to 99,5% less than half of respondents show willingness to pay in contrast with 73% when going from 99,5% to 100%. Out of 105 respondents, 55 show that their choices concerning pension products are inconsistent with classic utility theory. Financial background proves insignificant thus pointing to behavioral biases. As individuals make choices that leave them worse-off, we argue that pension plan design would highly benefit from public policy interventions.

Design and study of self-assembled functional organic and hybrid systems for biological applications

The focus of self-assembly as a strategy for the synthesis has been confined largely to molecules, because of the importance of manipulating the structure of matter at the molecular scale. We have investigated the influence of temperature and pH, in addition to the concentration of the capping agent used for the formation of the nano-bio conjugates. For example, the formation of the narrower size distribution of the nanoparticles was observed with the increase in the concentration of the protein, which supports the fact that γ-globulin acts both as a controller of nucleation as well as stabiliser. As analyzed through various photophysical, biophysical and microscopic techniques such as TEM, AFM, C-AFM, SEM, DLS, OPM, CD and FTIR, we observed that the initial photoactivation of γ-globulin at pH 12 for 3 h resulted in small protein fibres of ca. Further irradiation for 24 h, led to the formation of selfassembled long fibres of the protein of ca. 5-6 nm and observation of surface plasmon resonance band at around 520 nm with the concomitant quenching of luminescence intensity at 680 nm. The observation of light triggered self-assembly of the protein and its effect on controlling the fate of the anchored nanoparticles can be compared with the naturally occurring process such as photomorphogenesis.Furthermore,our approach offers a way to understand the role played by the self-assembly of the protein in ordering and knock out of the metal nanoparticles and also in the design of nano-biohybrid materials for medicinal and optoelectronic applications. Investigation of the potential applications of NIR absorbing and water soluble squaraine dyes 1-3 for protein labeling and anti-amyloid agents forms the subject matter of the third chapter of the thesis. The study of their interactions with various proteins revealed that 1-3 showed unique interactions towards serum albumins as well as lysozyme. 69%, 71% and 49% in the absorption spectra as well as significant quenching in the fluorescence intensity of the dyes 1-3, respectively. Half-reciprocal analysis of the absorption data and isothermal titration calorimetric (ITC) analysis of the titration experiments gave a 1:1 stoichiometry for the complexes formed between the lysozyme and squaraine dyes with association constants (Kass) in the range 104-105 M-1. We have determined the changes in the free energy (ΔG) for the complex formation and the values are found to be -30.78, -32.31 and -28.58 kJmol-1, respectively for the dyes 1, 2 and 3. Furthermore, we have observed a strong induced CD (ICD) signal corresponding to the squaraine chromophore in the case of the halogenated squaraine dyes 2 and 3 at 636 and 637 nm confirming the complex formation in these cases. To understand the nature of interaction of the squaraine dyes 1-3 with lysozyme, we have investigated the interaction of dyes 1-3 with different amino acids. These results indicated that the dyes 1-3 showed significant interactions with cysteine and glutamic acid which are present in the side chains of lysozyme. In addition the temperature dependent studies have revealed that the interaction of the dye and the lysozyme are irreversible. Furthermore, we have investigated the interactions of these NIR dyes 1-3 with β- amyloid fibres derived from lysozyme to evaluate their potential as inhibitors of this biologically important protein aggregation. These β-amyloid fibrils were insoluble protein aggregates that have been associated with a range of neurodegenerative diseases, including Huntington, Alzheimer’s, Parkinson’s, and Creutzfeldt-Jakob diseases. We have synthesized amyloid fibres from lysozyme through its incubation in acidic solution below pH 4 and by allowing to form amyloid fibres at elevated temperature. To quantify the binding affinities of the squaraine dyes 1-3 with β-amyloids, we have carried out the isothermal titration calorimetric (ITC) measurements. The association constants were determined and are found to be 1.2 × 105, 3.6× 105 and 3.2 × 105 M-1 for the dyes, 1-3, respectively. To gain more insights into the amyloid inhibiting nature of the squaraine dyes under investigations, we have carried out thioflavin assay, CD, isothermal titration calorimetry and microscopic analysis. The addition of the dyes 1-3 (5μM) led to the complete quenching in the apparent thioflavin fluorescence, thereby indicating the destabilization of β-amyloid fibres in the presence of the squaraine dyes. Further, the inhibition of the amyloid fibres by the squaraine dyes 1-3, has been evidenced though the DLS, TEM AFM and SAED, wherein we observed the complete destabilization of the amyloid fibre and transformation of the fibre into spherical particles of ca. These results demonstrate the fact that the squaraine dyes 1-3 can act as protein labeling agents as well as the inhibitors of the protein amyloidogenesis. The last chapter of the thesis describes the synthesis and investigation of selfassembly as well as bio-imaging aspects of a few novel tetraphenylethene conjugates 4-6.Expectedly, these conjugates showed significant solvatochromism and exhibited a hypsochromic shift (negative solvatochromism) as the solvent polarity increased, and these observations were justified though theoretical studies employing the B3LYP/6-31g method. We have investigated the self-assembly properties of these D-A conjugates though variation in the percentage of water in acetonitrile solution due to the formation of nanoaggregates. Further the contour map of the observed fluorescence intensity as a function of the fluorescence excitation and emission wavelength confirmed the formation of J-type aggregates in these cases. To have a better understanding of the type of self-assemblies formed from the TPE conjugates 4-6, we have carried out the morphological analysis through various microscopic techniques such as DLS, SEM and TEM. 70%, we observed rod shape architectures having ~ 780 nm in diameter and ~ 12 μM in length as evidenced through TEM and SEM analysis. We have made similar observations with the dodecyl conjugate 5 at ca. 70% and 50% water/acetonitrile mixtures, the aggregates formed from 4 and 5 were found to be highly crystalline and such structures were transformed to amorphous nature as the water fraction was increased to 99%. To evaluate the potential of the conjugate as bio-imaging agents, we have carried out their in vitro cytotoxicity and cellular uptake studies though MTT assay, flow cytometric and confocal laser scanning microscopic techniques. Thus nanoparticle of these conjugates which exhibited efficient emission, large stoke shift, good stability, biocompatibility and excellent cellular imaging properties can have potential applications for tracking cells as well as in cell-based therapies. In summary we have synthesized novel functional organic chromophores and have studied systematic investigation of self-assembly of these synthetic and biological building blocks under a variety of conditions. The investigation of interaction of water soluble NIR squaraine dyes with lysozyme indicates that these dyes can act as the protein labeling agents and the efficiency of inhibition of β-amyloid indicate, thereby their potential as anti-amyloid agents.

Reinventing the academic conference: how delegates design productive cities

During the 6th International Sustainable Food Planning Conference, the so-called Design LABs partly replaced the regular parallel sessions. The reason for this change was twofold. On the one hand it aims to break through an endless series of parallel presentations, and on the other hand the LAB’s aim was to produce innovative design solutions for increasing the amount of food production in the city. This article describes this experiment to enhance the delivery of urban design concepts, which could substantially produce more food than current models. During the conference each of the parallel sessions half of the time consisted of a design-LAB, in which participants were brought together around a map with the task to design a substantial amount of food productive spaces in the case study site. The results of this experiment were dual: 1. a very committed attitude of delegates to this part of the conference and 2. the design tasks resulted in innovative design results. These results not only emphasise the potential design measures onsite but also pledged for a strong and more intensive connectivity with the city and the landscape around it. This makes it possible to link the supply and use of resources with the typology of the region, hence determining an effective and productive urban agriculture system.

An Interpolative Analytical Cache Model with Application to Performance-Power Design Space Exploration

Caches are known to consume up to half of all system power in embedded processors. Co-optimizing performance and power of the cache subsystems is therefore an important step in the design of embedded systems, especially those employing application specific instruction processors. In this project, we propose an analytical cache model that succinctly captures the miss performance of an application over the entire cache parameter space. Unlike exhaustive trace driven simulation, our model requires that the program be simulated once so that a few key characteristics can be obtained. Using these application-dependent characteristics, the model can span the entire cache parameter space consisting of cache sizes, associativity and cache block sizes. In our unified model, we are able to cater for direct-mapped, set and fully associative instruction, data and unified caches. Validation against full trace-driven simulations shows that our model has a high degree of fidelity. Finally, we show how the model can be coupled with a power model for caches such that one can very quickly decide on pareto-optimal performance-power design points for rapid design space exploration.

Systems Design: Introduction to Systems

This is the introductory slides for Comp1209 Systems Design. In the first half we explain the structure of the course, and in the second we give a brief introduction to Systems (using Bloodhound SSC as a class exercise)

Acoustic Design in Urban Development : analysis of urban soundscapes and acoustic ecology research in New York City

The world is urbanizing rapidly with more than half of the global population now living in cities. Improving urban environments for the well-being of the increasing number of urban citizens is becoming one of the most important challenges of the 21st century. Even though it is common that city planners have visions of a ’good urban milieu’, those visions are concerning visual aesthetics or practical matters. The qualitative perspective of sound, such as sonic diversity and acoustic ecology are neglected aspects in architectural design. Urban planners and politicians are therefore largely unaware of the importance of sounds for the intrinsic quality of a place. Whenever environmental acoustics is on the agenda, the topic is noise abatement or noise legislation – a quantitative attenuation of sounds. Some architects may involve acoustical aspects in their work but sound design or acoustic design has yet to develop to a distinct discipline and be incorporated in urban planning.My aim was to investigate to what extent the urban soundscape is likely to improve if modern architectural techniques merge with principles of acoustics. This is an important, yet unexplored, research area. My study explores and analyses the acoustical aspects in urban development and includes interviews with practitioners in the field of urban acoustics, situated in New York City. My conclusion is that to achieve a better understanding of the human living conditions in mega-cities, there is a need to include sonic components into the holistic sense of urban development.

Type 14 Design B Port Side; Santa Louisa

print no 78, discoloration in upper half of print

An improved design procedure for LCC resonant filter of dimmable electronic ballasts for fluorescent lamps, based on lamp model

This paper presents an improved design methodology for the determination of the parameters used in the classical series-resonant parallel-loaded (SRPL) filter employed in the switching frequency controlled dimmable electronic ballasts. According to the analysis developed in this paper, it is possible to evaluate some important characteristics of the resonant filter during the dimming operation, such as: range of switching frequency, phase shift, and rms value of the current drained by the resonant filter + fluorescent lamp set. Experimental results are presented in order to validate the analyses developed in this paper. © 2005 IEEE.

An overview on a nonideal system with three and a half degrees of freedom

The present paper studies a system comprised of two blocks connected by springs and dampers, and a DC motor with limited power supply fixed on a block, characterizing a non-ideal problem. This DC motor exciting the system causes interactions between the motor and the structure supporting it. Because of that, the non-ideal mathematical formulation of the problem has one and a half extra degree of freedom than the ideal one. A suitable choice of physical parameters leads to internal resonance conditions, that is, its natural frequencies are multiple of each other, by a known integer quantity. The purpose here is to study the dynamic behavior of the system using an analytical method based on perturbation techniques. The literature shows that the averaging method is the more flexible method concerning non-ideal problems. Summarizing, an steady state solution in amplitude and phase coordinates was obtained with averaging method showing the dependence of the structure amplitudes with the rotation frequency of the motor. Moreover, this solution shows that on of the amplitude coordinates has influence in the determination of the stationary rotation frequency. The analytical solution obtained shows the presence of the rotation frequency in expressions representing the oscillations of the structure, and the presence of amplitude coordinates in expressions describing the dynamic motion of the DC motor. These characteristics show the influence not only of the motor on structure but also of the response of the structure on dynamical behavior of the motor. Copyright © 2005 by ASME.

O design gráfico e as mensagens socioambientais: a fotografia como linguagem no discurso do Greenpeace Brasil

Pós-graduação em Design - FAAC

Design e semântica: investigação de técnicas estatísticas para auxílio no projeto de produto

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)