74 resultados para STRUCTURE-BASED DRUG DESIGN


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This study contributes to the growth of design knowledge in China, where vehicle design for the local, older user is in its initial developmental stages. Therefore, this research has explored the travel needs of older Chinese vehicle users in order to assist designers to better understand users’ current and future needs. A triangulation method consisting of interviews, logbook and co-discovery was used to collect multiple forms of data and so explore the research question. Grounded theory has been employed to analyze the research data. This study found that users’ needs are reflected through various ‘meanings’ that they attach to vehicles – meanings that give a tangible expression to their experiences. This study identified six older-user need categories: (i) safety, (ii) utility, (iii) comfort, (iv) identity, (v) emotion and (vi) spirituality. The interrelationships among these six categories are seen as an interactive structure, rather than as a linear or hierarchical arrangement. Chinese cultural values, which are generated from particular local context and users’ social practice, will play a dynamic role in linking and shaping the travel needs of older vehicle users in the future. Moreover, this study structures the older-user needs model into three levels of meaning, to give guidance to vehicle design direction: (i) the practical meaning level, (ii) the social meaning level and (ii) the cultural meaning level. This study suggests that a more comprehensive explanation exists if designers can identify the vehicle’s meaning and property associated with the fulfilled older users’ needs. However, these needs will vary, and must be related to particular technological, social, and cultural contexts. The significance of this study lies in its contributions to the body of knowledge in three areas: research methodology, theory and design. These theoretical contributions provide a series of methodological tools, models and approaches from a vehicle design perspective. These include a conditional/consequential matrix, a travel needs identification model, an older users’ travel-related needs framework, a user information structure model, and an Older-User-Need-Based vehicle design approach. These models suggest a basic framework for the new design process which might assist in the design of new vehicles to fulfil the needs of future, aging Chinese generations. The models have the potential to be transferred to other design domains and different cultural contexts.

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One in five Australian workers believes that work doesn’t fit well with their family and social commitments. Concurrently, organisations are recognising that to stay competitive they need policies and practices that support the multiple aspects of employees’ lives. Many employees work in group environments yet there is currently little group level work-life balance research. This paper proposes a new theoretical framework developed to understand the design of work groups to better facilitate work-life balance. This new framework focuses on task and relational job designs, group structures and processes and workplace culture.

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In this paper, we present fully Bayesian experimental designs for nonlinear mixed effects models, in which we develop simulation-based optimal design methods to search over both continuous and discrete design spaces. Although Bayesian inference has commonly been performed on nonlinear mixed effects models, there is a lack of research into performing Bayesian optimal design for nonlinear mixed effects models that require searches to be performed over several design variables. This is likely due to the fact that it is much more computationally intensive to perform optimal experimental design for nonlinear mixed effects models than it is to perform inference in the Bayesian framework. In this paper, the design problem is to determine the optimal number of subjects and samples per subject, as well as the (near) optimal urine sampling times for a population pharmacokinetic study in horses, so that the population pharmacokinetic parameters can be precisely estimated, subject to cost constraints. The optimal sampling strategies, in terms of the number of subjects and the number of samples per subject, were found to be substantially different between the examples considered in this work, which highlights the fact that the designs are rather problem-dependent and require optimisation using the methods presented in this paper.

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Design based research (DBR) is an appropriate method for small scale educational research projects involving collaboration between teachers, students and researchers. It is particularly useful in collaborative projects where an intervention is implemented and evaluated in a grounded context. The intervention can be technological, or a new program required by policy changes. It can be applied to educational contexts, such as when English teachers undertake higher degree research projects in their own or others’ sites; or for academics working collaboratively as researchers with teams of teachers. In the case described here the paper shows that DBR is designed to make a difference in the real world contexts in which occurs.

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Glycosaminoglycans (GAGs) are important complex carbohydrates that participate in many biological processes through the regulation of their various protein partners. Biochemical, structural biology and molecular modelling approaches have assisted in understanding the molecular basis of such interactions, creating an opportunity to capitalize on the large structural diversity of GAGs in the discovery of new drugs. The complexity of GAG–protein interactions is in part due to the conformational flexibility and underlying sulphation patterns of GAGs, the role of metal ions and the effect of pH on the affinity of binding. Current understanding of the structure of GAGs and their interactions with proteins is here reviewed: the basic structures and functions of GAGs and their proteoglycans, their clinical significance, the three-dimensional features of GAGs, their interactions with proteins and the molecular modelling of heparin binding sites and GAG–protein interactions. This review focuses on some key aspects of GAG structure–function relationships using classical examples that illustrate the specificity of GAG–protein interactions, such as growth factors, anti-thrombin, cytokines and cell adhesion molecules. New approaches to the development of GAG mimetics as possible new glycotherapeutics are also briefly covered.

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An earlier CRC-CI project on ‘automatic estimating’ (AE) has shown the key benefit of model-based design methodologies in building design and construction to be the provision of timely quantitative cost evaluations. Furthermore, using AE during design improves design options, and results in improved design turn-around times, better design quality and/or lower costs. However, AEs for civil engineering structures do not exist; and research partners in the CRC-CI expressed interest in exploring the development of such a process. This document reports on these investigations. The central objective of the study was to evaluate the benefits and costs of developing an AE for concrete civil engineering works. By studying existing documents and through interviews with design engineers, contractors and estimators, we have established that current civil engineering practices (mainly roads/bridges) do not use model-based planning/design. Drawings are executed in 2D and only completed at the end of lengthy planning/design project management lifecycle stages. We have also determined that estimating plays two important, but different roles. The first is part of project management (which we have called macro level estimating). Estimating in this domain sets project budgets, controls quality delivery and contains costs. The second role is estimating during planning/design (micro level estimating). The difference between the two roles is that the former is performed at the end of various lifecycle stages, whereas the latter is performed at any suitable time during planning/design.

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This paper discusses about effectiveness of blogs for reflective learning in design education. Students in two animation units were asked to complete their online journal via blog in terms of reflective learning. Students were encouraged to respond their weekly outcomes and project development process to their blog and share it with other students. A survey was undertaken to evaluate their learning experience and one of the key outcomes indicates that interaction design for social network is significantly important to blog based learning design.

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Purpose: The purpose of the paper is to develop a framework for evaluation of accessibility for knowledge based cities. ----- ----- Design/methodology/approach: This approach notifies common mistakes and problems in accessibility assessment for knowledge cities. ----- ----- Originality/value: Accessibility plays a key role in transport sustainability and recognizes the crucial links between transport and sustainable goals like air quality, environmental resource consumption & social equity. In knowledge cities, accessibility has significant effects on quality of life and social equity by improving the mobility of people and goods. Accessibility also influences patterns of growth and economic health by providing access to land. Accessibility is not only one of the components of knowledge cities but also affects other elements of knowledge cities directly or indirectly. ----- ----- Practical implications: The outcomes of the application will be helpful for developing particular methodologies for evaluating knowledge cities. On other words, this methodology attempts to develop an assessment procedure for examining accessibility of knowledge-based cities.

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Shrinking product lifecycles, tough international competition, swiftly changing technologies, ever increasing customer quality expectation and demanding high variety options are some of the forces that drive next generation of development processes. To overcome these challenges, design cost and development time of product has to be reduced as well as quality to be improved. Design reuse is considered one of the lean strategies to win the race in this competitive environment. design reuse can reduce the product development time, product development cost as well as number of defects which will ultimately influence the product performance in cost, time and quality. However, it has been found that no or little work has been carried out for quantifying the effectiveness of design reuse in product development performance such as design cost, development time and quality. Therefore, in this study we propose a systematic design reuse based product design framework and developed a design leanness index (DLI) as a measure of effectiveness of design reuse. The DLI is a representative measure of reuse effectiveness in cost, development time and quality. Through this index, a clear relationship between reuse measure and product development performance metrics has been established. Finally, a cost based model has been developed to maximise the design leanness index for a product within the given set of constraints achieving leanness in design process.

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It is predicted that with increased life expectancy in the developed world, there will be a greater demand for synthetic materials to repair or regenerate lost, injured or diseased bone (Hench & Thompson 2010). There are still few synthetic materials having true bone inductivity, which limits their application for bone regeneration, especially in large-size bone defects. To solve this problem, growth factors, such as bone morphogenetic proteins (BMPs), have been incorporated into synthetic materials in order to stimulate de novo bone formation in the center of large-size bone defects. The greatest obstacle with this approach is that the rapid diffusion of the protein from the carrier material, leading to a precipitous loss of bioactivity; the result is often insufficient local induction or failure of bone regeneration (Wei et al. 2007). It is critical that the protein is loaded in the carrier material in conditions which maintains its bioactivity (van de Manakker et al. 2009). For this reason, the efficient loading and controlled release of a protein from a synthetic material has remained a significant challenge. The use of microspheres as protein/drug carriers has received considerable attention in recent years (Lee et al. 2010; Pareta & Edirisinghe 2006; Wu & Zreiqat 2010). Compared to macroporous block scaffolds, the chief advantage of microspheres is their superior protein-delivery properties and ability to fill bone defects with irregular and complex shapes and sizes. Upon implantation, the microspheres are easily conformed to the irregular implant site, and the interstices between the particles provide space for both tissue and vascular ingrowth, which are important for effective and functional bone regeneration (Hsu et al. 1999). Alginates are natural polysaccharides and their production does not have the implicit risk of contamination with allo or xeno-proteins or viruses (Xie et al. 2010). Because alginate is generally cytocompatible, it has been used extensively in medicine, including cell therapy and tissue engineering applications (Tampieri et al. 2005; Xie et al. 2010; Xu et al. 2007). Calcium cross-linked alginate hydrogel is considered a promising material as a delivery matrix for drugs and proteins, since its gel microspheres form readily in aqueous solutions at room temperature, eliminating the need for harsh organic solvents, thereby maintaining the bioactivity of proteins in the process of loading into the microspheres (Jay & Saltzman 2009; Kikuchi et al. 1999). In addition, calcium cross-linked alginate hydrogel is degradable under physiological conditions (Kibat PG et al. 1990; Park K et al. 1993), which makes alginate stand out as an attractive candidate material for the protein carrier and bone regeneration (Hosoya et al. 2004; Matsuno et al. 2008; Turco et al. 2009). However, the major disadvantages of alginate microspheres is their low loading efficiency and also rapid release of proteins due to the mesh-like networks of the gel (Halder et al. 2005). Previous studies have shown that a core-shell structure in drug/protein carriers can overcome the issues of limited loading efficiencies and rapid release of drug or protein (Chang et al. 2010; Molvinger et al. 2004; Soppimath et al. 2007). We therefore hypothesized that introducing a core-shell structure into the alginate microspheres could solve the shortcomings of the pure alginate. Calcium silicate (CS) has been tested as a biodegradable biomaterial for bone tissue regeneration. CS is capable of inducing bone-like apatite formation in simulated body fluid (SBF) and its apatite-formation rate in SBF is faster than that of Bioglass® and A-W glass-ceramics (De Aza et al. 2000; Siriphannon et al. 2002). Titanium alloys plasma-spray coated with CS have excellent in vivo bioactivity (Xue et al. 2005) and porous CS scaffolds have enhanced in vivo bone formation ability compared to porous β-tricalcium phosphate ceramics (Xu et al. 2008). In light of the many advantages of this material, we decided to prepare CS/alginate composite microspheres by combining a CS shell with an alginate core to improve their protein delivery and mineralization for potential protein delivery and bone repair applications

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The School of Electrical and Electronic Systems Engineering of Queensland University of Technology (like many other universities around the world) has recognised the importance of complementing the teaching of signal processing with computer based experiments. A laboratory has been developed to provide a "hands-on" approach to the teaching of signal processing techniques. The motivation for the development of this laboratory was the cliche "What I hear I remember but what I do I understand." The laboratory has been named as the "Signal Computing and Real-time DSP Laboratory" and provides practical training to approximately 150 final year undergraduate students each year. The paper describes the novel features of the laboratory, techniques used in the laboratory based teaching, interesting aspects of the experiments that have been developed and student evaluation of the teaching techniques

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Design for Manufacturing (DFM) is a highly integral methodology in product development, starting from the concept development phase, with the aim of improving manufacturing productivity. It is used to reduce manufacturing costs in complex production environments, while maintaining product quality. While Design for Assembly (DFA) is focusing on elimination or combination of parts with other components, which in most cases relates to performing a function and manufacture operation in a simpler way, DFM is following a more holistic approach. Common consideration for DFM are standard components, manufacturing tool inventory and capability, materials compatibility with production process, part handling, logistics, tool wear and process optimization, quality control complexity or Poka-Yoke design. During DFM, the considerable background work required for the conceptual phase is compensated for by a shortening of later development phases. Current DFM projects normally apply an iterative step-by-step approach and eventually transfer to the developer team. The study is introducing a new, knowledge based approach to DFM, eliminating steps of DFM, and showing implications on the work process. Furthermore, a concurrent engineering process via transparent interface between the manufacturing engineering and product development systems is brought forward.

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Many older people have difficulties using modern consumer products due to increased product complexity both in terms of functionality and interface design. Previous research has shown that older people have more difficulty in using complex devices intuitively when compared to the younger. Furthermore, increased life expectancy and a falling birth rate have been catalysts for changes in world demographics over the past two decades. This trend also suggests a proportional increase of older people in the work-force. This realisation has led to research on the effective use of technology by older populations in an effort to engage them more productively and to assist them in leading independent lives. Ironically, not enough attention has been paid to the development of interaction design strategies that would actually enable older users to better exploit new technologies. Previous research suggests that if products are designed to reflect people's prior knowledge, they will appear intuitive to use. Since intuitive interfaces utilise domain-specific prior knowledge of users, they require minimal learning for effective interaction. However, older people are very diverse in their capabilities and domain-specific prior knowledge. In addition, ageing also slows down the process of acquiring new knowledge. Keeping these suggestions and limitations in view, the aim of this study was set to investigate possible approaches to developing interfaces that facilitate their intuitive use by older people. In this quest to develop intuitive interfaces for older people, two experiments were conducted that systematically investigated redundancy (the use of both text and icons) in interface design, complexity of interface structure (nested versus flat), and personal user factors such as cognitive abilities, perceived self-efficacy and technology anxiety. All of these factors could interfere with intuitive use. The results from the first experiment suggest that, contrary to what was hypothesised, older people (65+ years) completed the tasks on the text only based interface design faster than on the redundant interface design. The outcome of the second experiment showed that, as expected, older people took more time on a nested interface. However, they did not make significantly more errors compared with younger age groups. Contrary to what was expected, older age groups also did better under anxious conditions. The findings of this study also suggest that older age groups are more heterogeneous in their capabilities and their intuitive use of contemporary technological devices is mediated more by domain-specific technology prior knowledge and by their cognitive abilities, than chronological age. This makes it extremely difficult to develop product interfaces that are entirely intuitive to use. However, by keeping in view the cognitive limitations of older people when interfaces are developed, and using simple text-based interfaces with flat interface structure, would help them intuitively learn and use complex technological products successfully during early encounter with a product. These findings indicate that it might be more pragmatic if interfaces are designed for intuitive learning rather than for intuitive use. Based on this research and the existing literature, a model for adaptable interface design as a strategy for developing intuitively learnable product interfaces was proposed. An adaptable interface can initially use a simple text only interface to help older users to learn and successfully use the new system. Over time, this can be progressively changed to a symbols-based nested interface for more efficient and intuitive use.

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Lyngbya majuscula is a cyanobacterium (blue-green algae) occurring naturally in tropical and subtropical coastal areas worldwide. Deception Bay, in Northern Moreton Bay, Queensland, has a history of Lyngbya blooms, and forms a case study for this investigation. The South East Queensland (SEQ) Healthy Waterways Partnership, collaboration between government, industry, research and the community, was formed to address issues affecting the health of the river catchments and waterways of South East Queensland. The Partnership coordinated the Lyngbya Research and Management Program (2005-2007) which culminated in a Coastal Algal Blooms (CAB) Action Plan for harmful and nuisance algal blooms, such as Lyngbya majuscula. This first phase of the project was predominantly of a scientific nature and also facilitated the collection of additional data to better understand Lyngbya blooms. The second phase of this project, SEQ Healthy Waterways Strategy 2007-2012, is now underway to implement the CAB Action Plan and as such is more management focussed. As part of the first phase of the project, a Science model for the initiation of a Lyngbya bloom was built using Bayesian Networks (BN). The structure of the Science Bayesian Network was built by the Lyngbya Science Working Group (LSWG) which was drawn from diverse disciplines. The BN was then quantified with annual data and expert knowledge. Scenario testing confirmed the expected temporal nature of bloom initiation and it was recommended that the next version of the BN be extended to take this into account. Elicitation for this BN thus occurred at three levels: design, quantification and verification. The first level involved construction of the conceptual model itself, definition of the nodes within the model and identification of sources of information to quantify the nodes. The second level included elicitation of expert opinion and representation of this information in a form suitable for inclusion in the BN. The third and final level concerned the specification of scenarios used to verify the model. The second phase of the project provides the opportunity to update the network with the newly collected detailed data obtained during the previous phase of the project. Specifically the temporal nature of Lyngbya blooms is of interest. Management efforts need to be directed to the most vulnerable periods to bloom initiation in the Bay. To model the temporal aspects of Lyngbya we are using Object Oriented Bayesian networks (OOBN) to create ‘time slices’ for each of the periods of interest during the summer. OOBNs provide a framework to simplify knowledge representation and facilitate reuse of nodes and network fragments. An OOBN is more hierarchical than a traditional BN with any sub-network able to contain other sub-networks. Connectivity between OOBNs is an important feature and allows information flow between the time slices. This study demonstrates more sophisticated use of expert information within Bayesian networks, which combine expert knowledge with data (categorized using expert-defined thresholds) within an expert-defined model structure. Based on the results from the verification process the experts are able to target areas requiring greater precision and those exhibiting temporal behaviour. The time slices incorporate the data for that time period for each of the temporal nodes (instead of using the annual data from the previous static Science BN) and include lag effects to allow the effect from one time slice to flow to the next time slice. We demonstrate a concurrent steady increase in the probability of initiation of a Lyngbya bloom and conclude that the inclusion of temporal aspects in the BN model is consistent with the perceptions of Lyngbya behaviour held by the stakeholders. This extended model provides a more accurate representation of the increased risk of algal blooms in the summer months and show that the opinions elicited to inform a static BN can be readily extended to a dynamic OOBN, providing more comprehensive information for decision makers.

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New advancement in genomics, proteomics, and metabonomics created significant excitement about the use of these relatively new technologies in drug design, discovery, development, and molecular-targeted therapeutics by identifying new drug targets and better tools for safety and efficacy studies in preclinical and clinical stages of drug development as well as diagnostics. In this chapter, we will briefly discuss the application of genomics, proteomics, and metabonomics in drug discovery and development