Pharmacophore Model of Cruzain Inhibitors

Chagas disease, caused by the protozoan Trypanosoma cruzi, is one of the most serious amongst the so-called neglected diseases in Latin America, specially in Brazil. So far there has been no effective treatment for the chronic phase of this disease. Cruzain is a major cysteine protease of T cruzi and it is recognized as a valid target for Chagas disease chemotherapy. The mechanism of cruzain action is associated with the nucleophilic attack of an activated sulfur atom towards electrophilic groups. In this report, features of a putative pharmacophore model of the enzyme, developed as a virtual screening tool for the selection of potential cruzain inhibitors, are described. The final proposed model was applied to the ZINC v.7 database and afterwards experimentally validated by an enzymatic inhibition assay. One of the compounds selected by the model showed cruzain inhibition in the low micromolar range.

MPO Inhibitors Selected by Virtual Screening

The hemeprotein myeloperoxidase (MPO) participates in innate immune defense through its ability to generate potent microbicidal oxidants. However, these oxidants are also key mediators of the tissue damage associated with many inflammatory diseases. Thus, there is considerable interest in developing therapeutically useful MPO inhibitors. Here, we used structure-based drug design (SBDD) and ligand-based drug design (LBDD) to select for potentially new and selective MPO inhibitors. A pharmacophore model was developed based on the crystal structure of human MPO in complex with salicylhydroxamic acid (SHA), a known inhibitor of the enzyme. The pharmacophore model was used to screen the ZINC database for potential ligands, which were further filtered on the basis of their physical-chemical properties and docking score. The filtered compounds were visually inspected, and nine were purchased for experimental studies. Surprisingly, almost all of the selected compounds belonged to the aromatic hydrazide class, which had been previously described as MPO inhibitors. The compounds selected by virtual screening were shown to inhibit the chlorinating activity of MPO; the top four compounds displayed IC(50) values ranging from 1.0 to 2.8 mM. MPO inactivation by the most effective compound was shown to be irreversible. Overall, our results show that SBDD and LBDD may be useful for the rational development of new MPO inhibitors.

Uncovering false positives on a virtual screening search for cruzain inhibitors

Some unexpected promiscuous inhibitors were observed in a virtual screening protocol applied to select cruzain inhibitors from the ZINC database. Physical-chemical and pharmacophore model filters were used to reduce the database size. The selected compounds were docked into the cruzain active site. Six hit compounds were tested as inhibitors. Although the compounds were designed to be nucleophilically attacked by the catalytic cysteine of cruzain, three of them showed typical promiscuous behavior, revealing that false positives are a prevalent concern in VS programs. (C) 2007 Elsevier Ltd. All rights reserved.

Nyttan med virtuella provrum : En utvärderingsstudie av virtuella provrum för online-shopping, med fokus på användbarhet.

Den relativt nya företeelsen BrandME – I am the brand är en eTjänst som fungerar som ett virtuellt provrum och därmed gör det möjligt att kunna prova på kläder virtuellt. Till sin hjälp har man bland annat använt sig av 3D-grafik samt databaser. BrandME är en produkt av det kanadensiska företaget My Virtual Model, ett företag som har arbetat med att sätta standarder för virtuell identitet sedan år 2000.Då denna företeelse är relativ ny, skapar detta utrymme för undersökning och bedömning om huruvida välutvecklad och välanpassad BrandME är. Undersökningens syfte är att utvärdera BrandME för att sedan kunna fastställa nyttan med denna eTjänst. Under utvärderingen koncentrerar vi oss dels på användbarheten hos BrandME och dels på utformningen av BrandME.

Building virtual learning communities

This chapter introduces the concept of virtual learning communities and discusses and further enhances the theory and definitions presented in related literature. A model comprising four criteria essential to virtual learning communities is presented and discussed in detail. Theory and case studies relating to the impact of virtual learning communities on distance education and students from diverse cultural groups are also examined. In addition, this chapter investigates the enabling technologies and facilitation that is required to build virtual learning communities. Other case studies are used to illustrate the process of building virtual learning communities. Emerging technologies such as wikis and video lectures are also analysed to determine the effects they have on building and sustaining effective virtual learning communities.

A conceptual model for sport services marketing research : integrating quality, value and satisfaction

This paper advances our understanding of the relationship between quality, value and satisfaction in the context of spectator sport services. This is achieved through an analysis and examination of relevant secondary data culminating in a conceptual model Although extensive research has been conducted in the three separate areas of quality, value and satisfaction, to date no work has been reported attempting to develop macro models that capture the concepts and their potential interrelationships. Such macro models could enhance the communication and stimulate further research for sport marketing scholars. This paper proposes a model apposite for further research and in the process leads to the potential confirmation, rejection or, indeed, adaptation of the conceplualization of sport services.

From e-learning to virtual learning community: bridging the gap

'Community' has become a buzz word in the E-Learning arena. This paper examines the concept of virtual community, in the context of E-Learning. It defines what constitutes a virtual community and virtual learning community. A model comprising four essential criteria that define a virtual learning community is proposed. These criteria are discussed with relation to Deakin University's E-Learning system. The paper concludes by highlighting the factors that may help bridge the gap between Deakin's present provision of E-Learning to the development of a virtual learning community.

More than just a transaction: conceptualising industry-based networks for virtual trading communities

This paper addresses the questions of why failure in industry-based networks has been so persistent and whether it is possible to avoid failure and achieve success in internet based markets [iMarketplaces]. A better explanation of implementation failures is important for both improved empirical outcomes and theory building. We construct a theoretical framework based on Bijker’s technology frame (1995) and a contextualization typology developed by Nowotny, Scott and Gibbons (2001). The framework helps us understand how industry-based networks function, why they fail and how we can apply the framework to assist better empirical outcomes. In this paper we apply our framework to Food Connect Australia, a vertically integrated marketplace, representative of the first wave of B2B markets. Sponsors of these iMarketplaces were quick to see and exploit the opportunities online access offered to bring together large numbers of buyers and sellers in new ways. However a lack of understanding of firstly, what represented true value in these networks and secondly, how to achieve buy-in at sustainable levels, meant that many of these first wave sites failed. Application of our framework reveals why there has been a radical shift from the trading role originally envisioned for these sites to the information hub model of the iMarketplace that industry is now being urged to adopt (Berryman and Heck, 2001).

A facility for the integration of live and virtual environments in realtime

This paper describes a research facility which has been established to explore the integration of live and virtual environments in real-time. The facility combines digital ontput from both live and electronic sources such as video, animatinos and 3D virtual environments and enables the monitoring and control of the interaction between live actors and the digital enviromnents. This provides a research environment in which the interaction between participants in the design and construction process and 3D virtual buildings can be investigated. This will lead to the enhancement of decision making and planning in the design and construction process.

Virtual experts : who's online?

There will be between 30 and 80 million online students in the world by 2025. Globally, school systems are investing huge resources in the development of online education programs in order to meet this demand. Related implications for online teaching have been largely ignored despite evidence of the greatly increased workload for online teachers and widespread student dissatisfaction with online leaming experiences. Opportunities for improving the online experience for both leamers and teachers revolve around minimizing procedural inefficiencies in dealing with large numbers of individual students, as opposed to a single class, and of enhancing students' social and cognitive engagement with leaming. Intelligent software agents that can automate many routine online tasks and some aspects of leamer interaction have enormous potential to facilitate this. These agents that can act as a personal online coach, mentor or tutor to increase the individualisation of learning. The development of evidence-based agent personas is essential if agents are to fulfil specific educational roles. CUITently there is little progress being made in this area because of the lack of an agentrole model that can be used to implement specific educational personas in agents. In this paper we discuss key foundational elements of the nature and basis for implementing elements of educational expertise in software and how this could be used in developing agent persona models for specific educational roles and a model for implementing pedagogical constructs in intelligent educational software.

Application of the adaptive reuse potential model in Hong Kong : a case study of Lui Seng Chun

There is an increasing complexity and interplay between all of the issues associated with property portfolio decisions. This paper explores the relationships between financial, environmental and social parameters associated with building adaptive reuse by way of a case study. A new model predicting adaptive reuse potential is applied to a heritage building in Hong Kong known as Lui Seng Chun. Such application can assist in the transformation of the building and property industry towards more sustainable practices, strategies and outcomes, by providing a means by which the industry can identify and rank existing buildings that have high potential for adaptive reuse. In Hong Kong's case it provides an ability for sustainable, responsive energy and natural resource management by allowing issues regarding excessive and inappropriate resource use to be identified and assessed, and appropriate management strategies to be implemented. Given the building's current age and condition, Lui Seng Chun has at least 25 years of physical life remaining. The further application of a multi-criteria sustainability evaluation tool supports the conclusion that an adaptive reuse strategy for this building will make a demonstrable contribution to the economic, social and environmental amenity of Hong Kong. The application of these techniques to other buildings with significant "embedded physical life" is highly recommended.

A virtual salesperson

This chapter describes the use of a graphical humane interface - a Virtual Salesperson. The face of the Virtual Salesperson is a generic Facial Animation Engine developed at the University of Genova in Italy and uses a 3-D computer graphics model based on the MPEG-4 standard supplemented by Cyberware scans for facial detail. The appearance of the head may be modified by Facial Definition Parameters to more accurately model the required visage allowing one model to represent many different Talking Heads. The “brain” of the Virtual Salesperson, developed at Curtin University, integrates natural language parsing, text to speech synthesis, and artificial intelligence systems to produce a “bot” capable of helping a user through a question/answer sales enquiry. The Virtual Salesperson is a specific example of a generic Human Computer Interface - a Talking Head.

Using knowledge management processes to develop and implement organisational training strategies for virtual teams : an action learning approach

This paper develops a conceptual model of a knowledge management system that could be used to develop and implement organizational training strategies for virtual teams. An action research-based case is presented to support and illustrate the contention that action-learning methods can be effectively used to enable and tap into the knowledge generated by virtual teams. Virtual teams are an increasingly common response to changing organizational needs. However, the use of virtual teams has outpaced our understanding of their dynamics and unique characteristics. Practitioners are now offering virtual team training, but few organizations are making the effort to offer in-house training. Moreover, they are missing out on the opportunity to systematically capture the knowledge produced by virtual teams and cycle it back into virtual team training and support systems.

Towards a universal and integrated digital representation of physical phenomena: a model to investigate comfort and energy efficiency in future environments

This thesis describes the exploration and the development of computational means to investigate the behaviour of design objects before they are available for investigation in the physical world. The motivation is to inform the design process about the design object's performance in order to achieve better--more performance-oriented--design outcomes in the sense of energy efficiency and comfort performance than can be achieved by conventional design techniques.

Aura, real-time motion capture dance and 3D stereoscopic dance

Aura explored the potential of motion capture and 3D stereo projection to visualize 1950's dance philosopher, Susanne K. Langer's notion of 'virtual force'.