74 resultados para STRUCTURE-BASED DRUG DESIGN


Relevância:

100.00% 100.00%

Publicador:

Resumo:

Overarching Research Questions Are ACT motorists aware of roadside saliva based drug testing operations? What is the perceived deterrent impact of the operations? What factors are predictive of future intentions to drug drive? What are the differences between key subgroups

Relevância:

100.00% 100.00%

Publicador:

Resumo:

The fungal metabolite 3-chloro-4-hydroxyphenylacetic acid (1) was utilized in the generation of a unique drug-like screening library using parallel solution-phase synthesis. A 20-membered amide library (3–22) was generated by first converting 1 to methyl (3-chloro-4-hydroxyphenyl)acetate (2), then reacting this scaffold with a diverse series of primary amines via a solvent-free aminolysis procedure. The structures of the synthetic analogues (3–22) were elucidated by spectroscopic data analysis. The structures of compounds 8, 12, and 22 were confirmed by single X-ray crystallographic analysis. All compounds were evaluated for cytotoxicity against a human prostate cancer cell line (LNCaP) and for antiparasitic activity toward Trypanosoma brucei brucei and Plasmodium falciparum and showed no significant activity at 10 μM. The library was also tested for effects on the lipid content of LNCaP and PC-3 prostate cancer cells, and it was demonstrated that the fluorobenzyl analogues (12–14) significantly reduced cellular phospholipid and neutral lipid levels.

Relevância:

100.00% 100.00%

Publicador:

Resumo:

This study proposes an optimized approach of designing in which a model specially shaped composite tank for spacecrafts is built by applying finite element analysis. The composite layers are preliminarily designed by combining quasi-network design method with numerical simulation, which determines the ratio between the angle and the thickness of layers as the initial value of the optimized design. By adopting an adaptive simulated annealing algorithm, the angles and the numbers of layers at each angle are optimized to minimize the weight of structure. Based on this, the stacking sequence of composite layers is formulated according to the number of layers in the optimized structure by applying the enumeration method and combining the general design parameters. Numerical simulation is finally adopted to calculate the buckling limit of tanks in different designing methods. This study takes a composite tank with a cone-shaped cylinder body as example, in which ellipsoid head section and outer wall plate are selected as the object to validate this method. The result shows that the quasi-network design method can improve the design quality of composite material layer in tanks with complex preliminarily loading conditions. The adaptive simulated annealing algorithm can reduce the initial design weight by 30%, which effectively probes the global optimal solution and optimizes the weight of structure. It can be therefore proved that, this optimization method is capable of designing and optimizing specially shaped composite tanks with complex loading conditions.

Relevância:

100.00% 100.00%

Publicador:

Resumo:

In the structure of the title complex [[Na(H2O)3]+ (C6H2Cl3N2O2)-^ . 3(H2O)]n, the Na salt of the herbicide picloram, the cation is a polymeric chain structure, based on doubly water-bridged NaO5 trigonal bipyramidal complex units which have in addition, a singly-bonded monodentate water molecule. Each of the bridges within the chain which lies along the a cell direction is centrosymmetric with Na...Na separations of 3.4807(16) and 3.5109(16)Ang. In the crystal, there are three water molecules of solvation and these, as well as the coordinated water molecules and the amino group of the 4-amino-3,5,6-trichloropicolinate anion are involved in extensive inter-species hydrogen-bonding interactions with carboxyl and water O-atoms as well as the pyridine N-atom. Among these association is a centrosymmetric cyclic tetra-water R4/4(8) ring , resulting in an overall three-dimensional structure.

Relevância:

100.00% 100.00%

Publicador:

Resumo:

This paper reports on the current field of narrative-based game design through case study analysis with a particular focus on balancing high narrative agency with low production resources.

Relevância:

100.00% 100.00%

Publicador:

Resumo:

Purpose The purpose of this paper is to identify the financial barriers to the supply of affordable apartments in Australia and examine whether demand aggregation and ‘deliberative development’ (self-build) can form a new affordable housing ‘structure of provision’. Design/methodology/approach Market design, an offshoot of game theory, is used to analyse the existing apartment development model, with ‘deliberative development’ proposed as an innovative alternative. Semi-structured interviews with residential development financiers are used to evaluate whether deliberative development could obtain the requisite development finance. Findings Our investigation into the financial barriers of a deliberative development model suggest that while there are hurdles, these can be addressed if key risks in the exchange process can be mitigated. Hence, affordability can be enhanced by ‘deliberative development’ replacing the existing speculative development model. Research implications Market design is a new innovative theoretical approach to understanding the supply of housing, offering practical solutions to affordable apartment supply in Australia. Originality/value This research identifies financial barriers to the supply of affordable apartments; introduces theoretical understandings gained from market design as an innovative solution; provides evidence that a new structure of building provision based on ‘deliberative development’ could become a key means of achieving more affordable and better designed apartments.

Relevância:

100.00% 100.00%

Publicador:

Resumo:

CXCL-8 (Interleukin 8) is a CXC chemokine with a central role in the human immune response. We have undertaken extensive in silico analyses to elucidate the interactions of CXCL-8 with its various binding partners, which are crucial for its biological function. Sequence and structure analyses showed that residues in the thirdq β-sheet and basic residues in the heparin binding site are highly variable, while residues in the second β-sheet are highly conserved. Molecular dynamics simulations in aqueous solution of dimeric CXCL-8 have been performed with starting geometries from both X-ray and NMR structures showed shearing movements between the two antiparallel C-terminal helices. Dynamic conservation analyses of these simulations agreed with experimental data indicating that structural differences between the two structures at quaternary level arise from changes in the secondary structure of the N-terminal loop, the 310-helix, the 30s, 40s, and 50s loops and the third β-sheet, resulting in a different interhelical separation. Nevertheless, the observation of these different states indicates that CXCL-8 has the potential to undergo conformational changes, and it seems likely that this feature is relevant to the mode of binding of glycosaminoglycan (GAG) mimetics such as cyclitols. Simulations of the receptor peptide fragment−CXCL-8 complex identified several specific interactions of the receptor peptide with CXCL-8 that could be exploited in the structure-based design of competitive peptides and nonpeptidic molecules targeting CXCL-8 for combating inflammatory diseases. Simulations of the CXCL-8 dimer complexed with a 24-mer heparin fragment and of the CXCL-8−receptor peptide complex revealed that Arg60, Lys64, and Arg68 in the dimer bind to cyclitols in a horseshoe pattern, defining a region which is spatially distinct from the receptor binding site. There appears to be an optimum number of sulfates and an optimum length of alkyl spacers required for the interaction of cyclitol inhibitors with the dimeric form of CXCL-8. Calculation of the binding affinities of cyclitol inhibitors reflected satisfactorily the ranking of experimentally determined inhibitory potencies. The findings of these molecular modeling studies will help in the search for inhibitors which can modulate various CXCL-8 biological activities and serve as an excellent model system to study CXC-inhibitor interactions.

Relevância:

100.00% 100.00%

Publicador:

Resumo:

SCOOT is a hybrid event combining the web, mobile devices, public displays and cultural artifacts across multiple public parks and museums in an effort to increase the perceived and actual access to cultural participation by everyday people. The research field is locative game design and the context was the re-invigoration of public sites as a means for exposing the underlying histories of sites and events. The key question was how to use game play technologies and processes within everyday places in ways that best promote playful and culturally meaningful experiences whilst shifting the loci of control away from commercial and governmental powers. The research methodology was primarily practice led underpinned by ethnographic and action research methods. In 2004 SCOOT established itself as a national leader in the field by demonstrating innovative methods for stimulating rich interactions across diverse urban places using technically-augmented game play. Despite creating a sophisticated range of software and communication tools SCOOT most dramatically highlighted the role of the ubiquitous mobile phone in facilitating socially beneficial experiences. Through working closely with the SCOOT team, collaborating organisations developed important new knowledge around the potential of new technologies and processes for motivating, sustaining and reinvigorating public engagement. Since 2004, SCOOT has been awarded $600,00 in competitive and community funding as well as countless in kind support from partner organisations such as Arts Victoria, National Gallery of Victoria, Melbourne Museum, Australian Centre for the Moving Image, Federation Square, Art Centre of Victoria, The State Library of Victoria, Brisbane River Festival, State Library of Queensland, Brisbane Maritime Museum, Queensland University of Technology, and Victoria University.

Relevância:

100.00% 100.00%

Publicador:

Resumo:

Aided by the development of information technology, the balance of power in the market place is rapidly shifting from marketers towards consumers and nowhere is this more obvious than in the online environment (Denegri-Knott, Zwick, & Schroeder, 2006; Moynagh & Worsley, 2002; Newcomer, 2000; Samli, 2001). From the inception and continuous development of the Internet, consumers are becoming more empowered. They can choose what they want to click on the Internet, they can shop and transact payments, watch and download video, chat with others, be it friends or even total strangers. Especially in online communities, like-minded consumers share and exchange information, ideas and opinions. One form of online community is the online brand community, which gathers specific brand lovers. As with any social unit, people form different roles in the community and exert different effects on each other. Their interaction online can greatly influence the brand and marketers. A comprehensive understanding of the operation of this special group form is essential to advancing marketing thought and practice (Kozinets, 1999). While online communities have strongly shifted the balance of power from marketers to consumers, the current marketing literature is sparse on power theory (Merlo, Whitwell, & Lukas, 2004). Some studies have been conducted from an economic point of view (Smith, 1987), however their application to marketing has been limited. Denegri-Knott (2006) explored power based on the struggle between consumers and marketers online and identified consumer power formats such as control over the relationship, information, aggregation and participation. Her study has built a foundation for future power studies in the online environment. This research project bridges the limited marketing literature on power theory with the growing recognition of online communities among marketing academics and practitioners. Specifically, this study extends and redefines consumer power by exploring the concept of power in online brand communities, in order to better understand power structure and distribution in this context. This research investigates the applicability of the factors of consumer power identified by Denegri-Knott (2006) to the online brand community. In addition, by acknowledging the model proposed by McAlexander, Schouten, & Koenig (2002), which emphasized that community study should focus on the role of consumers and identifying multiple relationships among the community, this research further explores how member role changes will affect power relationships as well as consumer likings of the brand. As a further extension to the literature, this study also considers cultural differences and their effect on community member roles and power structure. Based on the study of Hofstede (1980), Australia and China were chosen as two distinct samples to represent differences in two cultural dimensions, namely individualism verses collectivism and high power distance verses low power distance. This contribution to the research also helps answer the research gap identified by Muñiz Jr & O'Guinn (2001), who pointed out the lack of cross cultural studies within the online brand community context. This research adopts a case study methodology to investigate the issues identified above. Case study is an appropriate research strategy to answer “how” and “why” questions of a contemporary phenomenon in real-life context (Yin, 2003). The online brand communities of “Haloforum.net” in Australia and “NGA.cn” in China were selected as two cases. In-depth interviews were used as the primary data collection method. As a result of the geographical dispersion and the preference of a certain number of participants, online synchronic interviews via MSN messenger were utilized along with the face-to-face interviews. As a supplementary approach, online observation was carried over two months, covering a two week period prior to the interviews and a six week period following the interviews. Triangulation techniques were used to strengthen the credibility and validity of the research findings (Yin, 2003). The findings of this research study suggest a new definition of power in an online brand community. This research also redefines the consumer power types and broadens the brand community model developed by McAlexander et al. (2002) in an online context by extending the various relationships between brand and members. This presents a more complete picture of how the perceived power relationships are structured in the online brand community. A new member role is discovered in the Australian online brand community in addition to the four member roles identified by Kozinets (1999), in contrast however, all four roles do not exist in the Chinese online brand community. The research proposes a model which links the defined power types and identified member roles. Furthermore, given the results of the cross-cultural comparison between Australia and China showed certain discrepancies, the research suggests that power studies in the online brand community should be country-specific. This research contributes to the body of knowledge on online consumer power, by applying it to the context of an online brand community, as well as considering factors such as cross cultural difference. Importantly, it provides insights for marketing practitioners on how to best leverage consumer power to serve brand objective in online brand communities. This, in turn, should lead to more cost effective and successful communication strategies. Finally, the study proposes future research directions. The research should be extended to communities of different sizes, to different extents of marketer control over the community, to the connection between online and offline activities within the brand community, and (given the cross-cultural findings) to different countries. In addition, a greater amount of research in this area is recommended to determine the generalizability of this study.

Relevância:

100.00% 100.00%

Publicador:

Resumo:

Although transformative learning theory remains one of the most influential theories in the field of adult education, studies on fostering transformative learning, particularly in groups and in the workplace, remain sparse. This article summarises some evidence of transformational learning that influenced changes to practice, processes, and the organisational culture in a case study. It is based on a cohort of 12 worker-learners enrolled in a Graduate Certificate in Education (Executive Leadership) course offered by an Australian university (Queensland University of Technology). Data for this article were drawn from interviews with 10 participants, a focus group with 6 of them, their assessment presentations, and reflective notes of the course facilitators. Also included here are the effects on transformational learning of Taylor’s five elements of work-based learning design, Fuller and Unwins’ features of expansive learning, and Billett’s workplace pedagogies.

Relevância:

100.00% 100.00%

Publicador:

Resumo:

Oberon-2 is an object-oriented language with a class structure based on type extension. The runtime structure of Oberon-2 is described and the low-level mechanism for dynamic type checking explained. It is shown that the superior type-safety of the language, when used for programming styles based on heterogeneous, pointer-linked data structures, has an entirely negligible cost in runtime performance.

Relevância:

100.00% 100.00%

Publicador:

Resumo:

This research study investigated the factors that influenced the development of teacher identity in a small cohort of mature-aged graduate pre-service teachers over the course of a one-year Graduate Diploma program (Middle Years). It sought to illuminate the social and relational dynamics of these pre-service teachers’ experiences as they began new ways of being and learning during a newly introduced one-year Graduate Diploma program. A relational-ontological perspective underpinned the relational-cultural framework that was applied in a workshop program as an integral part of this research. A relational-ontological perspective suggests that the development of teacher identity is to be construed more as an ontological process than an epistemological one. Its focus is more on questions surrounding the person and their ‘becoming’ a teacher than about the knowledge they have or will come to have. Hence, drawing on work by researchers such as Alsup (2006), Gilligan, (1982), Isaacs, (2007), Miller (1976), Noddings, (2005), Stout (2001), and Taylor, (1989), teacher identity was defined as an individual pre-service teacher’s unique sense of self as a teacher that included his or her beliefs about teaching and learning (Alsup, 2006; Stout, 2001; Walkington, 2005). Case-study was the preferred methodology within which this research project was framed, and narrative research was used as a method to document the way teacher identity was shaped and negotiated in discursive environments such as teacher education programs, prior experiences, classroom settings and the practicum. The data that was collected included student narratives, student email written reflections, and focus group dialogue. The narrative approach applied in this research context provided the depth of data needed to understand the nature of the mature-aged pre-service teachers’ emerging teacher identities and experiences in the graduate diploma program. Findings indicated that most of the mature-aged graduate pre-service teachers came in to the one-year graduate diploma program with a strong sense of personal and professional selves and well-established reasons why they had chosen to teach Middle Years. Their choice of program involved an expectation of support and welcome to a middle-school community and culture. Two critical issues that emerged from the pre-service teachers’ narratives were the importance they placed on the human support including the affirmation of themselves and their emerging teacher identities. Evidence from this study suggests that the lack of recognition of preservice teachers’ personal and professional selves during the graduate diploma program inhibited the development of a positive middle-school teacher identity. However, a workshop program developed for the participants in this research and addressing a range of practical concerns to beginning teachers offered them a space where they felt both a sense of belonging to a community and where their thoughts and beliefs were recognized and valued. Thus, the workshops provided participants with the positive social and relational dynamics necessary to support them in their developing teacher identities. The overall findings of this research study strongly indicate a need for a relational support structure based on a relational-ontological perspective to be built into the overall course structure of Graduate Pre-service Diplomas in Education to support the development of teacher identity. Such a support structure acknowledges that the pre-service teacher’s learning and formation is socially embedded, relational, and a continual, lifelong process.

Relevância:

100.00% 100.00%

Publicador:

Resumo:

For the fabrication of tissue engineering scaffolds, the intended tissue formation process imposes requirements on the architecture. The chosen porosity often is a tradeoff between volume and surface area accessible to cells, and mechanical properties of the construct. Interconnectivity of the pores is essential for cell migration through the scaffold and for mass transport. Conventional techniques such as salt leaching often result in heterogeneous structures and do not allow for a precise control of the architecture. Stereolithography is a rapid prototyping method that can be utilised to make 3D constructs with high spatial control by radical photopolymerisation. In this study, a regular structure based on cyclic repetition of cell units were designed through CAD modelling.. One of these structures was built on a stereolithography apparatus (SLA). Furthermore, a polylactide-based resin was developed that can be applied in stereolithography. Polylactide has proven before to be a well-performing polymer in bone tissue engineering. The final objective in this study is to build newly designed PDLLA scaffolds with a precise SLA fabrication technique to study the effect of scaffold architecture on mechanical and biological properties.

Relevância:

100.00% 100.00%

Publicador:

Resumo:

For a biomaterial to be considered suitable for bone repair it should ideally be both bioactive and have a capacity for controllable drug delivery; as such, mesoporous SiO2 glass has been proposed as a new class of bone regeneration material by virtue of its high drug-loading ability and generally good biocompatibility. It does, however, have less than optimum bioactivity and controllable drug delivery properties. In this study, we incorporated strontium (Sr) into mesoporous SiO2 in an effort to develop a bioactive mesoporous SrO–SiO2 (Sr–Si) glass with the capacity to deliver Sr2+ ions, as well as a drug, at a controlled rate, thereby producing a material better suited for bone repair. The effects of Sr2+ on the structure, physiochemistry, drug delivery and biological properties of mesoporous Sr–Si glass were investigated. The prepared mesoporous Sr–Si glass was found to have an excellent release profile of bioactive Sr2+ ions and dexamethasone, and the incorporation of Sr2+ improved structural properties, such as mesopore size, pore volume and specific surface area, as well as rate of dissolution and protein adsorption. The mesoporous Sr–Si glass had no cytotoxic effects and its release of Sr2+ and SiO44− ions enhanced alkaline phosphatase activity – a marker of osteogenic cell differentiation – in human bone mesenchymal stem cells. Mesoporous Sr–Si glasses can be prepared to porous scaffolds which show a more sustained drug release. This study suggests that incorporating Sr2+ into mesoporous SiO2 glass produces a material with a more optimal drug delivery profile coupled with improved bioactivity, making it an excellent material for bone repair applications. Keywords: Mesoporous Sr–Si glass; Drug delivery; Bioactivity; Bone repair; Scaffolds

Relevância:

100.00% 100.00%

Publicador:

Resumo:

This article applies social network analysis techniques to a case study of police corruption in order to produce findings which will assist in corruption prevention and investigation. Police corruption is commonly studied but rarely are sophisticated tools of analyse engaged to add rigour to the field of study. This article analyses the ‘First Joke’ a systemic and long lasting corruption network in the Queensland Police Force, a state police agency in Australia. It uses the data obtained from a commission of inquiry which exposed the network and develops hypotheses as to the nature of the networks structure based on existing literature into dark networks and criminal networks. These hypotheses are tested by entering the data into UCINET and analysing the outcomes through social network analysis measures of average path distance, centrality and density. The conclusions reached show that the network has characteristics not predicted by the literature.