877 resultados para Pharmaceutics and Drug Design


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Optimisation is a fundamental step in the turbine design process, especially in the development of non-classical designs of radial-inflow turbines working with high-density fluids in low-temperature Organic Rankine Cycles (ORCs). The present work discusses the simultaneous optimisation of the thermodynamic cycle and the one-dimensional design of radial-inflow turbines. In particular, the work describes the integration between a 1D meanline preliminary design code adapted to real gases and the performance estimation approach for radial-inflow turbines in an established ORC cycle analysis procedure. The optimisation approach is split in two distinct loops; the inner operates on the 1D design based on the parameters received from the outer loop, which optimises the thermodynamic cycle. The method uses parameters including brine flow rate, temperature and working fluid, shifting assumptions such as head and flow coefficients into the optimisation routine. The discussed design and optimisation method is then validated against published benchmark cases. Finally, using the same conditions, the coupled optimisation procedure is extended to the preliminary design of a radial-inflow turbine with R143a as working fluid in realistic geothermal conditions and compared against results from commercially-available software RITAL from Concepts-NREC.

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The discipline of architecture focuses on designing the built environment in response to the needs of society, reflecting culture through materials and forms. The physical boundaries of the city have become blurred through the integration of digital media, connecting the physical environment with the digital. In the recent past the future was imagined as highly technological; Ridley Scott’s Blade Runner is set in 2019 and introduces a polluted world where supersized screens inject advertisements in the cluttered urban space. Now, in 2014 screens are central to everyday life, but in a completely different way in respect to what had been imagined. Through ubiquitous computing and social media, information is abundant. Digital technologies have changed the way people relate to urban form supporting discussion on multiple levels, allowing citizens to be more vocal than ever before. Bottom-up campaigns to oppose anticipated developments or to suggest intervention in the way cities are designed, are a common situation in several parts of the world. For some extent governments and local authorities are trying to engage with developing technologies, but a common issue is that social media cannot be controlled or filtered as can be done with more traditional consultation methods. We question how designers can use the affordances of urban informatics to obtain and navigate useful social information to inform architectural and urban design. This research investigates different approaches to engage communities in the debate on the built environment. Physical and digital discussions have been initiated to capture citizens’ opinions on the use and design of public places. Online platforms, urban screens, mobile apps and guerrilla techniques are explored in the context of Brisbane, Australia.

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Traditional Islamic teachings and traditions involve guidelines that have direct applications in the domestic sphere. The principles of privacy, modesty, and hospitality are central to these guidelines; each principle has a significant effect on the design of Muslim homes, as well as on the organization of space and domestic behaviors within each home. This paper reviews literature on the privacy, modesty, and hospitality within Muslim homes. Nineteen publications from 1986 to 2013 were selected and analyzed for content related to the meaning of privacy, modesty, and hospitality in Islam and the design of Muslim homes. Despite the commonly shared guidelines for observing privacy, modesty, and hospitality within each home, Muslims living in different countries are influenced by cultural factors that operate within their country of residence. These factors help to shape the architectural styles and use of space within Muslim homes in different ways. Awareness of the multifactorial nature of the influences on the Muslim perception of home and the use of space is necessary for architects, building designers, engineers, and builders to be properly equipped to meet the needs of clients.

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This chapter examines the tools and activities (referred to as approaches) used by a catalyst while facilitating a design-led transformation within an Australian manufacturing small to medium enterprise (SME). Design-led innovation (DLI) aids the use of design at a higher strategic level; however few existing studies investigate the relative influence of approaches used by a catalyst while helping a firm to make a transition in the utilisation of design, specifically from a styling tool to a strategic process. This paper identifies the triggers to encouraging a shift toward understanding, utilising and valuing the business level outcomes of design through a range of design tools and activities within the participating company. Through a 12 month action research program, staff interviews and a reflective journal were utilised as data collection techniques to assess the successfulness of the approaches used during this project. It was found that, through the use of both successful and unsuccessful approaches, the catalyst achieved two key outcomes within the firm: 1) Improvements in the firm’s ability to challenge internal assumptions and standard practices; and 2) the creation of an informed and accurate awareness of company and industry issues. Approaches that made a higher impact of the firm were deemed successful, and were generally relatable to the task at hand, as perceived by employees. Additionally, the sequence in which the approaches were utilised was found to have a direct influence on their successfulness. Learnings from this research will assist future catalysts to facilitate a design-led transformation within a manufacturing SME through the use of design tools and activities with greater effectiveness.

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Multidrug resistance (MDR) occurs in prostate cancer, and this happens when the cancer cells resist chemotherapeutic drugs by pumping them out of the cells. MDR inhibitors such as cyclosporin A (CsA) can stop the pumping and enhance the drugs accumulated in the cells. The cellular drug accumulation is monitored using a microfluidic chip mounted on a single cell bioanalyzer. This equipment has been developed to measure accumulation of drugs such as doxorubicin (DOX) and fluorescently labeled paclitaxel (PTX) in single prostate cancer cells. The inhibition of drug efflux on the same prostate cell was examined in drug-sensitive and drug-resistant cells. Accumulation of these drug molecules was not found in the MDR cells, PC-3 RX-DT2R cells. Enhanced drug accumulation was observed only after treating the MDR cell in the presence of 5 μM of CsA as the MDR inhibitor. We envision this monitoring of the accumulation of fluorescent molecules (drug or fluorescent molecules), if conducted on single patient cancer cells, can provide information for clinical monitoring of patients undergoing chemotherapy in the future.

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Many complex aeronautical design problems can be formulated with efficient multi-objective evolutionary optimization methods and game strategies. This book describes the role of advanced innovative evolution tools in the solution, or the set of solutions of single or multi disciplinary optimization. These tools use the concept of multi-population, asynchronous parallelization and hierarchical topology which allows different models including precise, intermediate and approximate models with each node belonging to the different hierarchical layer handled by a different Evolutionary Algorithm. The efficiency of evolutionary algorithms for both single and multi-objective optimization problems are significantly improved by the coupling of EAs with games and in particular by a new dynamic methodology named “Hybridized Nash-Pareto games”. Multi objective Optimization techniques and robust design problems taking into account uncertainties are introduced and explained in detail. Several applications dealing with civil aircraft and UAV, UCAV systems are implemented numerically and discussed. Applications of increasing optimization complexity are presented as well as two hands-on test cases problems. These examples focus on aeronautical applications and will be useful to the practitioner in the laboratory or in industrial design environments. The evolutionary methods coupled with games presented in this volume can be applied to other areas including surface and marine transport, structures, biomedical engineering, renewable energy and environmental problems.

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The home environment is conceptualised in prolific ways within the academic literature. A home is an unparalleled base for human settlement and habitation that embodies a sensorial space that is layered with personal memories and traces of history. The success of a home in providing a strong ‘sense of place’ depends on various factors such as geographical location, monetary funds or personal perceptions. A home too, is an influential medium that allows its dwellers to express, perform and continue their cultural traditions and religious faiths. Traditional Islamic teachings and practices involve guidelines that apply directly to the domestic space. The principles of privacy, modesty and hospitality are paramount to these guidelines and each has a significant influence upon the design of Muslim homes and the home owners’ or dwellers’ domestic behaviours. Despite a significant increase of Muslim population in Australia over the last decade, very little is known about their perceptions of domestic life and their use of domestic spaces within an Australian context. This research investigated on how Muslims in Brisbane live and adapt within their Australian homes and if these homes meet their personal and familial needs to perform their daily activities, as well as maintaining and practising their Islamic faiths and traditions. Specific attention has been given to their perceptions on tripartite principles of privacy, modesty, and hospitality (PMH) and how they achieve these three objectives. A qualitative case study approach was used to investigate six Muslim families living in four Brisbane suburbs, consisting of: a) Case Study 1: three Muslim families residing in one suburb of Brisbane and, b) Case Study 2: three international Muslim students living in three different Brisbane suburbs. This research indicates that apart from minor ‘design-related’ difficulties, case study participants were able to continue to perform their daily activities within their current homes through minor changes to the use of the available interior spaces. Above all, case study participants opined that their current Australian homes provide them with adequate safety and privacy for their families without any major disturbances. Insight gained from these cases suggests that greater research attention needs to be given to the potential development of Australian home designs that are adaptable to the ever-changing needs of the Australian multicultural society. Awareness of the multifactorial nature of the influences on Muslims’ perceptions of home and their use of domestic space is needed if architects, building designers, engineers and builders are to be properly equipped to meet the needs of their Muslim clients.

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Anthony Dunne’s Hertzian Tales is an exploration of the aesthetic and conceptual aspects of industrial design and its potential to bring about social change for the users of electronic objects. It is a provoking and – to first-time readers – positively alarming social commentary on the interrelationship between electronic product design and culture, and the powerful but largely under-explored potential of electronic innovation to trigger social awareness. Hertzian Tales proposes an innovative approach to critical design and therefore serves as a reflection on and a critique of the commercial design practices at large. In this second edition, Dunne reiterates the original rationale for his project: a concern that the majority of industrial designers have unwittingly joined a treadmill culture of post-industrial mass-production – turning out electronic goods that have long simply met the brief of an optimally functioning and eagerly consumable technology.

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The climate in the Arctic is changing faster than anywhere else on earth. Poorly understood feedback processes relating to Arctic clouds and aerosol–cloud interactions contribute to a poor understanding of the present changes in the Arctic climate system, and also to a large spread in projections of future climate in the Arctic. The problem is exacerbated by the paucity of research-quality observations in the central Arctic. Improved formulations in climate models require such observations, which can only come from measurements in situ in this difficult-to-reach region with logistically demanding environmental conditions. The Arctic Summer Cloud Ocean Study (ASCOS) was the most extensive central Arctic Ocean expedition with an atmospheric focus during the International Polar Year (IPY) 2007–2008. ASCOS focused on the study of the formation and life cycle of low-level Arctic clouds. ASCOS departed from Longyearbyen on Svalbard on 2 August and returned on 9 September 2008. In transit into and out of the pack ice, four short research stations were undertaken in the Fram Strait: two in open water and two in the marginal ice zone. After traversing the pack ice northward, an ice camp was set up on 12 August at 87°21' N, 01°29' W and remained in operation through 1 September, drifting with the ice. During this time, extensive measurements were taken of atmospheric gas and particle chemistry and physics, mesoscale and boundary-layer meteorology, marine biology and chemistry, and upper ocean physics. ASCOS provides a unique interdisciplinary data set for development and testing of new hypotheses on cloud processes, their interactions with the sea ice and ocean and associated physical, chemical, and biological processes and interactions. For example, the first-ever quantitative observation of bubbles in Arctic leads, combined with the unique discovery of marine organic material, polymer gels with an origin in the ocean, inside cloud droplets suggests the possibility of primary marine organically derived cloud condensation nuclei in Arctic stratocumulus clouds. Direct observations of surface fluxes of aerosols could, however, not explain observed variability in aerosol concentrations, and the balance between local and remote aerosols sources remains open. Lack of cloud condensation nuclei (CCN) was at times a controlling factor in low-level cloud formation, and hence for the impact of clouds on the surface energy budget. ASCOS provided detailed measurements of the surface energy balance from late summer melt into the initial autumn freeze-up, and documented the effects of clouds and storms on the surface energy balance during this transition. In addition to such process-level studies, the unique, independent ASCOS data set can and is being used for validation of satellite retrievals, operational models, and reanalysis data sets.

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A major challenge in human genetics is to devise a systematic strategy to integrate disease-associated variants with diverse genomic and biological data sets to provide insight into disease pathogenesis and guide drug discovery for complex traits such as rheumatoid arthritis (RA)1. Here we performed a genome-wide association study meta-analysis in a total of >100,000 subjects of European and Asian ancestries (29,880 RA cases and 73,758 controls), by evaluating ~10 million single-nucleotide polymorphisms. We discovered 42 novel RA risk loci at a genome-wide level of significance, bringing the total to 101 (refs 2, 3, 4). We devised an in silico pipeline using established bioinformatics methods based on functional annotation5, cis-acting expression quantitative trait loci6 and pathway analyses7, 8, 9—as well as novel methods based on genetic overlap with human primary immunodeficiency, haematological cancer somatic mutations and knockout mouse phenotypes—to identify 98 biological candidate genes at these 101 risk loci. We demonstrate that these genes are the targets of approved therapies for RA, and further suggest that drugs approved for other indications may be repurposed for the treatment of RA. Together, this comprehensive genetic study sheds light on fundamental genes, pathways and cell types that contribute to RA pathogenesis, and provides empirical evidence that the genetics of RA can provide important information for drug discovery.

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The method of generalised estimating equations for regression modelling of clustered outcomes allows for specification of a working matrix that is intended to approximate the true correlation matrix of the observations. We investigate the asymptotic relative efficiency of the generalised estimating equation for the mean parameters when the correlation parameters are estimated by various methods. The asymptotic relative efficiency depends on three-features of the analysis, namely (i) the discrepancy between the working correlation structure and the unobservable true correlation structure, (ii) the method by which the correlation parameters are estimated and (iii) the 'design', by which we refer to both the structures of the predictor matrices within clusters and distribution of cluster sizes. Analytical and numerical studies of realistic data-analysis scenarios show that choice of working covariance model has a substantial impact on regression estimator efficiency. Protection against avoidable loss of efficiency associated with covariance misspecification is obtained when a 'Gaussian estimation' pseudolikelihood procedure is used with an AR(1) structure.

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This paper analyses the performance of particular wave-energy converter that uses the gyroscopic effects of a large rotating fly-wheel in combination with a controlled power-take-off device. Controlled gyroscopic forces have been used successfully in the past to reduce the motion of marine structures. With appropriately designed power-take-off elements, gyroscopic forces can be controlled to optimise the extracted energy from the motion of marine structures.

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- Introduction There is limited understanding of how young adults’ driving behaviour varies according to long-term substance involvement. It is possible that regular users of amphetamine-type stimulants (i.e. ecstasy (MDMA) and methamphetamine) may have a greater predisposition to engage in drink/drug driving compared to non-users. We compare offence rates, and self-reported drink/drug driving rates, for stimulant users and non-users in Queensland, and examine contributing factors. - Methods The Natural History Study of Drug Use is a prospective longitudinal study using population screening to recruit a probabilistic sample of amphetamine-type stimulant users and non-users aged 19-23 years. At the 4 ½ year follow-up, consent was obtained to extract data from participants’ Queensland driver records (ATS users: n=217, non-users: n=135). Prediction models were developed of offence rates in stimulant users controlling for factors such as aggression and delinquency. - Results Stimulant users were more likely than non-users to have had a drink-driving offence (8.7% vs. 0.8%, p < 0.001). Further, about 26% of ATS users and 14% of non-users self-reported driving under the influence of alcohol during the last 12 months. Among stimulant users, drink-driving was independently associated with last month high-volume alcohol consumption (Incident Rate Ratio (IRR): 5.70, 95% CI: 2.24-14.52), depression (IRR: 1.28, 95% CI: 1.07-1.52), low income (IRR: 3.57, 95% CI: 1.12-11.38), and male gender (IRR: 5.40, 95% CI: 2.05-14.21). - Conclusions Amphetamine-type stimulant use is associated with increased long-term risk of drink-driving, due to a number of behavioural and social factors. Inter-sectoral approaches which target long-term behaviours may reduce offending rates.