Mechanism‐based selection of a potent kallikrein‐related peptidase 7 inhibitor from a versatile library based on the sunflower trypsin inhibitor SFTI‐1

Potent and specific enzyme inhibition is a key goal in the development of therapeutic inhibitors targeting proteolytic activity. The backbone-cyclized peptide, Sunflower Trypsin Inhibitor (SFTI-1) affords a scaffold that can be engineered to achieve both these aims. SFTI-1's mechanism of inhibition is unusual in that it shows fast-on/slow-off kinetics driven by cleavage and religation of a scissile bond. This phenomenon was used to select a nanomolar inhibitor of kallikrein-related peptidase 7 (KLK7) from a versatile library of SFTI variants with diversity tailored to exploit distinctive surfaces present in the active site of serine proteases. Inhibitor selection was achieved through the use of size exclusion chromatography to separate protease/inhibitor complexes from unbound inhibitors followed by inhibitor identification according to molecular mass ascertained by mass spectrometry. This approach identified a single dominant inhibitor species with molecular weight of 1562.4 Da, which is consistent with the SFTI variant SFTI-WCTF. Once synthesized individually this inhibitor showed an IC50 of 173.9 ± 7.6 nM against chromogenic substrates and could block protein proteolysis. Molecular modeling analysis suggested that selection of SFTI-WCTF was driven by specific aromatic interactions and stabilized by an enhanced internal hydrogen bonding network. This approach provides a robust and rapid route to inhibitor selection and design.

The laws of the virtual worlds

What if you could check out of your world, and enter a place where the social environment was different, where real world laws didn't apply, and where the political system could be anything you wanted it to be? What if you could socialize there with family and friends, build your own palace, go skiing, and even hold down a job there? And what if there wasn't one alternate world, there were hundreds, and what if millions of people checked out of Earth and went there every day? Virtual worlds - online worlds where millions of people come to interact, play, and socialize - are a new type of social order. In this Article, we examine the implications of virtual worlds for our understanding of law, and demonstrate how law affects the interests of those within the world. After providing an extensive primer on virtual worlds, including their history and function, we examine two fundamental issues in detail. First, we focus on property, and ask whether it is possible to say that virtual world users have real world property interests in virtual objects. Adopting economic accounts that demonstrate the real world value of these objects and the exchange mechanisms for trading these objects, we show that, descriptively, these types of objects are indistinguishable from real world property interests. Further, the normative justifications for property interests in the real world apply - sometimes more strongly - in the virtual worlds. Second, we discuss whether avatars have enforceable legal and moral rights. Avatars, the user-controlled entities that interact with virtual worlds, are a persistent extension of their human users, and users identify with them so closely that the human-avatar being can be thought of as a cyborg. We examine the issue of cyborg rights within virtual worlds and whether they may have real world significance. The issues of virtual property and avatar rights constitute legal challenges for our online future. Though virtual worlds may be games now, they are rapidly becoming as significant as real-world places where people interact, shop, sell, and work. As society and law begin to develop within virtual worlds, we need to have a better understanding of the interaction of the laws of the virtual worlds with the law of this world.

A platform - independent product library for BIM

There is considerable interest internationally in developing product libraries to support the use of BIM. Product library initiatives are driven by national bodies, manufacturers and private companies who see their potential. A major issue with the production and distribution of product information for BIM is that separate library objects need to be produced for all of the different software systems that are going to use the library. This increases the cost of populating product libraries and also increases the difficulty in maintaining consistency between the representations for the different software over time. This paper describes a project which uses “software transformation” technology from the field of software engineering to support the definition of a single generic representation of a product which can then be automatically converted to the format required by receiving software. The paper covers the current state of implementation of the product library, the technology underlying the transformations for the currently supported software and the business model for creating a national library in Australia. This is placed within the context of other current product library systems to highlight the differences. The responsibilities of the various actors involved in supporting the product library are also discussed.

Mothers influencing mothers : the use of virtual discussion boards and their influence on consumption

Mothers represent a large segment of marketing dollars and traditionally, word of mouth was spread from mother to mother in a face-to-face environment, such as the school car park or mother’s groups. As families have evolved, so too has the traditional mother’s group. Limited academic studies have explored online mothers’ groups and how they impact on consumption. In order to explore the nature of this online influence and how mothers are influenced by other mothers online, a study was conducted through the use of observation and qualitative questioning. The data suggests that trust between mothers is generally high and mothers tend to trust the opinions of other mothers when they recommend a product. This is similar in other reference group contexts, however, mothers are communicating about brands frequently and influencing behaviour. This leads to a number of managerial and theoretical implications discussed in the paper.

Using social media to create a participatory library service : an Australian study

Public libraries are increasingly using social media in an attempt to meet users in their own spaces. Social media can be useful when used to create a participatory library service – to engage with users. However, there has been little empirical investigation into the success of social media use by public libraries. This article reports on the findings of a research project that explored the use of social media by Australian public libraries. Two organisations participated in case studies that involved interviews, document analysis, and social media observation. To contextualise the use of social media in the case study organisations, a sub study was undertaking involving observation of an additional 24 public libraries across Australia. This article focuses on the findings from the observation sub study. It presents and applies a methodology for classifying social media content to determine whether the sample libraries’ social media use is indicative of a participatory approach to service delivery. This article explores how a range of social media platforms are used by the sample libraries and considers what ‘best practice’ in participatory library service looks like. The two case study organisations’ use of social media is highlighted as exemplary practice.

Australian Aboriginal virtual heritage

The thesis uses creative practice and Indigenous knowledge frameworks with design methods to explore the ways in which virtual technology can represent Indigenous history and culture.

International virtual networking capabilities and firm performance: A study of international entrepreneurial Australian SMEs

The Internet is a critical resource for a new generation of small and medium sized enterprise. Specifically, the Internet is important for small entrepreneurial firms in pursuing international opportunities through increased digital integration. As such, the Internet has been identified as a key enabler of international entrepreneurship (Reuber & Fischer, 2011). By facilitating international business for many entrepreneurial SMEs, the Internet has the ability to increase the quality and speed of communications, lower transaction costs, and facilitate the development of international networks. Although the Internet has been found to play a pivotal role in the creation of international relationships and is a mechanism for the creation of international growth opportunities in SMEs (Mathews & Healy, 2008), the role of the international entrepreneurial decision-maker in the development of international virtual networks for leveraging opportunities in internationalisation remains unclear. The findings of this research indicate that developing an ‘international virtual network capability’ forms an important part of the firm’s resource and more specifically dynamic capability base, which is just one component of a firm’s resource bundle that builds towards successful internationalisation via an Internet platform.

Indonesian LIS professionals’ understanding of Library 2.0 : a pilot study

The literature around Library 2.0 remains largely theoretical with few empirically studies and is particularly limited in developing countries such as Indonesia. This study addresses this gap and aims to provide information about the current state of knowledge on Indonesian LIS professionals’ understanding of Library 2.0. The researchers used qualitative and quantitative approaches for this study, asking thirteen closed- and open-ended questions in an online survey. The researchers used descriptive and in vivo coding to analyze the responses. Through their analysis, they identified three themes: technology, interactivity, and awareness of Library 2.0. Respondents demonstrated awareness of Library 2.0 and a basic understanding of the roles of interactivity and technology in libraries. However, overreliance on technology used in libraries to conceptualize Library 2.0 without an emphasis on its core characteristics and principles could lead to the misalignment of limited resources. The study results will potentially strengthen the research base for Library 2.0 practice, as well as inform LIS curriculum in Indonesia so as to develop practitioners who are able to adapt to users’ changing needs and expectations. It is expected that the preliminary data of this study could be used to design a much larger and more complex future research project in this area.

Conceptualising the learning organisation : creating a maturity framework to develop a shared understanding of the library's role in literacy and learning

Although they sit outside the formal education sector, libraries are intrinsically centres of learning where people can engage with knowledge and ideas and acquire the literacy skills that are essential for active participation in an increasingly digital society. In Australia, National and State Libraries Australasia (NSLA) has acknowledged the need to not only better understand the general concept of the library as a learning institution, but also to help the individual NSLA libraries specifically identify their capabilities in this arena. The NSLA Literacy and Learning project aimed to improve the members' organisational comprehension and practice as learning institutions and to help them conceptualise their ability to deliver literacy and learning programmes that will benefit their staff and their communities. The NSLA concept of learning institution encompassed two discrete lenses: the internal lens of the library's own organisational understanding and practice, and the external lens of the clients who engage in the literacy and learning programmes delivered by the library. The ultimate goal was to develop a matrix which could enable libraries to assess their perceived levels of maturity as learning institutions along a continuum of emerging to active capabilities. The matrix should also serve as a tool for shared understanding about the NSLA's own strategic directions in the literacy and learning space. This case study documents the evolving process of developing a learning institution maturity framework for libraries that considers individual, team and organisational learning, as well as clients' interactions with the organisation, with the goal of producing a framework that has the potential to measure the value of learning and growth in both the library's staff and the library's communities

The role of interpersonal influence in budget decision making: The Canadian public library experience

This study determined factors which influenced Canadian provincial (state) politicians when making funding decisions for public libraries. Using the case study methodology, Canadian provincial/state-level funding for public libraries in the 2009-2010 fiscal year was examined. The data were analyzed to determine whether Cialdini’s theory of influence and specifically any of the six tactics of influence (i.e., commitment and consistency, authority, liking, social proof, scarcity, and reciprocity) were instrumental in these budgetary decision-making processes. Findings show the principles of “authority,” “consistency and commitment,” and “liking” were relevant, and that “liking” was especially important to these decisions.

Virtual resistance based active damping solution for constant power instability in AC microgrids

With ever-increasing share of power electronic loads constant power instability is becoming a significant issue in microgrids, especially when they operate in the islanding mode. Transient conditions like resistive load-shedding or sudden increase of constant power loads (CPL) might destabilize the whole system. Modeling and stability analysis of AC microgrids with CPLs have already been discussed in literature. However, no effective solutions are provided to stabilize this kind of system. Therefore, this paper proposes a virtual resistance based active damping method to eliminate constant power instability in AC microgrids. Advantages and limitations of the proposed method are also discussed in detail. Simulation results are presented to validate the proposed active damping solution.

Augmenting and assisting model elicitation tasks with 3D virtual world context metadata

Accurate process model elicitation continues to be a time consuming task, requiring skill on the part of the interviewer to extract explicit and tacit process information from the interviewee. Many errors occur in this elicitation stage that would be avoided by better activity recall, more consistent specification methods and greater engagement in the elicitation process by interviewees. Theories of situated cognition indicate that interactive 3D representations of real work environments engage and prime the cognitive state of the viewer. In this paper, our major contribution is to augment a previous process elicitation methodology with virtual world context metadata, drawn from a 3D simulation of the workplace. We present a conceptual and formal approach for representing this contextual metadata, integrated into a process similarity measure that provides hints for the business analyst to use in later modelling steps. Finally, we conclude with examples from two use cases to illustrate the potential abilities of this approach.

A random key genetic algorithm for live migration of multiple virtual machines in data centers

Live migration of multiple Virtual Machines (VMs) has become an integral management activity in data centers for power saving, load balancing and system maintenance. While state-of-the-art live migration techniques focus on the improvement of migration performance of an independent single VM, only a little has been investigated to the case of live migration of multiple interacting VMs. Live migration is mostly influenced by the network bandwidth and arbitrarily migrating a VM which has data inter-dependencies with other VMs may increase the bandwidth consumption and adversely affect the performances of subsequent migrations. In this paper, we propose a Random Key Genetic Algorithm (RKGA) that efficiently schedules the migration of a given set of VMs accounting both inter-VM dependency and data center communication network. The experimental results show that the RKGA can schedule the migration of multiple VMs with significantly shorter total migration time and total downtime compared to a heuristic algorithm.