Non-combinatorial library screening reveals subsite cooperativity and identifies new high-efficiency substrates for kallikrein-related peptidase 14

An array of substrates link the tryptic serine protease, kallikrein-related peptidase 14 (KLK14), to physiological functions including desquamation and activation of signaling molecules associated with inflammation and cancer. Recognition of protease cleavage sequences is driven by complementarity between exposed substrate motifs and the physicochemical signature of an enzyme's active site cleft. However, conventional substrate screening methods have generated conflicting subsite profiles for KLK14. This study utilizes a recently developed screening technique, the sparse matrix library, to identify five novel high-efficiency sequences for KLK14. The optimal sequence, YASR, was cleaved with higher efficiency (k(cat)/K(m)=3.81 ± 0.4 × 10(6) M(-1) s(-1)) than favored substrates from positional scanning and phage display by 2- and 10-fold, respectively. Binding site cooperativity was prominent among preferred sequences, which enabled optimal interaction at all subsites as indicated by predictive modeling of KLK14/substrate complexes. These simulations constitute the first molecular dynamics analysis of KLK14 and offer a structural rationale for the divergent subsite preferences evident between KLK14 and closely related KLKs, KLK4 and KLK5. Collectively, these findings highlight the importance of binding site cooperativity in protease substrate recognition, which has implications for discovery of optimal substrates and engineering highly effective protease inhibitors.

Ownership structure and concentration and the timeliness of corporate earnings : Malaysian evidence

This thesis provides the first evidence on how ownership concentration and structure relate to the timeliness of price discovery and reporting lags in Malaysia. Based on a sample of 1,276 Malaysian firms from 1996 to 2009, the results show that ownership concentration and the identity of the largest shareholder matter to the timeliness of price discovery and reporting lags. Specifically, closely-held firms are more timely in their price discovery and have shorter reporting lags, particularly if the largest shareholder is a foreigner or a financial institution. Government-owned firms have longer reporting lags, as expected, but we find no evidence that family-owned firms have significantly different timeliness of price discovery and reporting lags than other firms. Additional analysis shows that prior to the implementation of the Malaysian Code of Corporate Governance, firms were more timely in their price discovery but longer in their reporting lag.

Cold and heat waves in the United States

Extreme cold and heat waves, characterised by a number of cold or hot days in succession, place a strain on people’s cardiovascular and respiratory systems. The increase in deaths due to these waves may be greater than that predicted by extreme temperatures alone. We examined cold and heat waves in 99 US cities for 14 years (1987–2000) and investigated how the risk of death depended on the temperature threshold used to define a wave, and a wave’s timing, duration and intensity. We defined cold and heat waves using temperatures above and below cold and heat thresholds for two or more days. We tried five cold thresholds using the first to fifth percentiles of temperature, and five heat thresholds using the ninety-fifth to ninety-ninth percentiles. The extra wave effects were estimated using a two-stage model to ensure that their effects were estimated after removing the general effects of temperature. The increases in deaths associated with cold waves were generally small and not statistically significant, and there was even evidence of a decreased risk during the coldest waves. Heat waves generally increased the risk of death, particularly for the hottest heat threshold. Cold waves of a colder intensity or longer duration were not more dangerous. Cold waves earlier in the cool season were more dangerous, as were heat waves earlier in the warm season. In general there was no increased risk of death during cold waves above the known increased risk associated with cold temperatures. Cold or heat waves earlier in the cool or warm season may be more dangerous because of a build up in the susceptible pool or a lack of preparedness for cold or hot temperatures.

Knowing and teaching the indigenous other : teachers’ engagement with Aboriginal and Torres Strait Islander cultures

This is the first empirical study of teacher knowledge and classroom practice in Aboriginal and Torres Strait Islander education. It describes the construction of a survey instrument to measure non-Indigenous Australian teachers’ knowledge of Indigenous culture and place, frequency of everyday intercultural exchanges, and attempts to integrate Indigenous knowledge into classroom practice. Many teachers reported low levels of knowledge of Indigenous cultures, and limited encounters outside of school. While the cohort expressed dissatisfaction with pre-service training, exposure to pre- and in-service courses in Indigenous education correlated with higher levels of cultural knowledge and cultural engagement. Teachers with higher levels of cultural engagement were more likely to attempt to integrate Indigenous knowledges in curriculum and pedagogy.

Editorial : promoting integrated development for smart and sustainable built environment

Purpose – This purpose of this paper is to introduce the new Smart and Sustainable Built Environment (SASBE) journal to readers by discussing the background and underlying principles of its establishment, the editorial visions, and the range of papers selected in this first issue. It will encourage readers and potential authors to consider the need for integrated approaches to sustainability problems, to take on emerging challenges in the built environment and to join the SASBE journal in finding and promoting optimum solutions. Design/methodology/approach – This paper explores the evolving nature of sustainability, the recent trends of sustainability endeavours in built environment and the current knowledge gaps. The need to bridge these gaps is then discussed in the context of suggested remedies and justifications. This leads to the development of a smart and sustainable built environment as a R&D philosophy for world researchers as part of their interactions with professional bodies and agencies such as CIB, UNEP and iiSBE, and the establishment of the SASBE journal. Findings – Sustainable development in the built environment requires holistic thinking and decision making and innovative solutions that enhance sustainability and result in mutually beneficial outcomes for all stakeholders. A dedicated forum, through the journal of SASBE, is much needed for the exploration, discussion, debate, and promotion of these integrated approaches. Originality/value – Through presenting an overview of the current issues and identifying gaps in the understanding and pursuit of sustainability in the built environment, this paper suggests potential areas for future research and practice as well as possible topics for authors to make new contributions.

Physical and linkage maps for Drosophila serrata, a model species for studies of clinal adaptation and sexual selection

Drosophila serrata is a member of the montium group, which contains more than 98 species and until recently was considered a subgroup within the melanogaster group. This Drosophila species is an emerging model system for evolutionary quantitative genetics and has been used in studies of species borders, clinal variation and sexual selection. Despite the importance of D. serrata as a model for evolutionary research, our poor understanding of its genome remains a significant limitation. Here, we provide a first-generation gene-based linkage map and a physical map for this species. Consistent with previous studies of other drosophilids we observed strong conservation of genes within chromosome arms homologous with D. melanogaster but major differences in within-arm synteny. These resources will be a useful complement to ongoing genome sequencing efforts and QTL mapping studies in this species

Digital archives and cultural memory : discovering lost histories in digitised Australian children's literature 1851-1945

A recent Australian literature digitisation project uncovered some surprising discoveries in the children’s books that it digitised. The Children’s Literature Digital Resources (CLDR) Project digitised children’s books that were first published between 1851 to 1945 and made them available online through AustLit: The Australian Literature Resource. The digitisation process also preserved, within the pages of those books, a range of bookplates, book labels, inscriptions, and loose ephemera. This material allows us to trace the provenance of some of the digitised works, some of which came from the personal libraries of now-famous authors, and others from less celebrated sources. These extra-textual traces can contribute to cultural memory of the past by providing evidence of how books were collected and exchanged, and what kinds of books were presented as prizes in schools and Sunday schools. They also provide insight into Australian literary and artistic networks, particularly of the first few decades of the 20th century. This article describes the kinds of material uncovered in the digitisation process and suggests that the material provides insights into literary and cultural histories that might otherwise be forgotten. It also argues that the indexing of this material is vital if it is not to be lost to future researchers.

Facebook, Twitter, SMS and YouTube : the ramifications and risks for surgeons

Social media revolution has impacted on how people interact with one another. This has been a worldwide phenomenon. Whilst social media had its genesis in the personal and private realm its use has expanded exponentially to professional and business contexts, as well as being adopted by governments, politicians, journalists – everyone in just about every walk of life. Although at first the uptake was slow, surgeons and other health professionals are now using social media in their professional as well as personal capacity. This comes with significant advantages and opportunities for improving surgical practice and for facilitating attending communication, but it also comes with certain risks, including legal liability. This paper outlines the ways in which social media including, Facebook, Twitter, YouTube and SMS, is increasingly being employed in surgical practice and explains the legal and ethical consequences that may inadvertently arise in its official, as well as, unofficial use.

Detecting conversing groups of chatters : a model, algorithms, and tests

Chatrooms, for example Internet Relay Chat, are generally multi-user, multi-channel and multiserver chat-systems which run over the Internet and provide a protocol for real-time text-based conferencing between users all over the world. While a well-trained human observer is able to understand who is chatting with whom, there are no efficient and accurate automated tools to determine the groups of users conversing with each other. A precursor to analysing evolving cyber-social phenomena is to first determine what the conversations are and which groups of chatters are involved in each conversation. We consider this problem in this paper. We propose an algorithm to discover all groups of users that are engaged in conversation. Our algorithms are based on a statistical model of a chatroom that is founded on our experience with real chatrooms. Our approach does not require any semantic analysis of the conversations, rather it is based purely on the statistical information contained in the sequence of posts. We improve the accuracy by applying some graph algorithms to clean the statistical information. We present some experimental results which indicate that one can automatically determine the conversing groups in a chatroom, purely on the basis of statistical analysis.

Confucius institutes and the rise of china

Abstract: Since 2004 China has set up over 700 Confucius Institutes and Confucius Classrooms around the world to promote its language and culture and thereby to shape its image. Despite this impressive number Confucius Institutes are surprisingly understudied, especially in terms of their actual structure, operation mode and activities. This paper uses German Confucius Institutes as a case study to bridge this gap. It first discusses the concepts of public and cultural diplomacy and culture institutes as a conceptual tool to analyze Confucius Institutes. It then turns to the case study to provide empirical data to better understand this instrument of China’s image shaping efforts. It argues that Confucius Institutes are connected to the rise of China and a unique member of the family of national culture institutes.

Data requirements and graph data structures for a multi-modal, multi-objective trip planner

Traffic congestion has a significant impact on the economy and environment. Encouraging the use of multimodal transport (public transport, bicycle, park’n’ride, etc.) has been identified by traffic operators as a good strategy to tackle congestion issues and its detrimental environmental impacts. A multi-modal and multi-objective trip planner provides users with various multi-modal options optimised on objectives that they prefer (cheapest, fastest, safest, etc) and has a potential to reduce congestion on both a temporal and spatial scale. The computation of multi-modal and multi-objective trips is a complicated mathematical problem, as it must integrate and utilize a diverse range of large data sets, including both road network information and public transport schedules, as well as optimising for a number of competing objectives, where fully optimising for one objective, such as travel time, can adversely affect other objectives, such as cost. The relationship between these objectives can also be quite subjective, as their priorities will vary from user to user. This paper will first outline the various data requirements and formats that are needed for the multi-modal multi-objective trip planner to operate, including static information about the physical infrastructure within Brisbane as well as real-time and historical data to predict traffic flow on the road network and the status of public transport. It will then present information on the graph data structures representing the road and public transport networks within Brisbane that are used in the trip planner to calculate optimal routes. This will allow for an investigation into the various shortest path algorithms that have been researched over the last few decades, and provide a foundation for the construction of the Multi-modal Multi-objective Trip Planner by the development of innovative new algorithms that can operate the large diverse data sets and competing objectives.

Intellectual property, TRIPS and development

Intellectual property is crucial to the promotion of innovation. It provides an incentive to innovate as well as security for investment in innovation. The industries of the 21st century-information technology, biotechnology, pharmaceuticals, communications, education and entertainment – are all knowledge-based. The WTO Agreement on Trade-Related Aspects of Intellectual Property Rights (the TRIPS Agreement), adopted in 1994 at the conclusion of the Uruguay Round of trade negotiations, requires all WTO member countries to provide for the protection and enforcement of intellectual property rights. Having forged a link for the first time between intellectual property rights and the international trading system, the adoption of TRIPS means that any country that aims to participate fully in the global economy needs to understand the role of intellectual property and align its intellectual property laws and practices with the international minimum standards prescribed by TRIPS. However, for developing and least-developed countries, the implementation of intellectual property systems and enforcement mechanisms raises questions and challenges. Does recognition and enforcement of intellectual property serve their development needs and objectives? Does TRIPS encourage or hinder the transfer of technologies to developing and least-developed countries, particularly those that meet urgent needs in areas such as public health, food security, water and energy? What is the effect of TRIPS on developing countries’ access to knowledge and information? Is there scope for flexibility in implementation of TRIPS in pursuit of development strategies?

Compaction control of topography and fault network structure along strike-slip faults in sedimentary basins

Strike-slip faults commonly display structurally complex areas of positive or negative topography. Understanding the development of such areas has important implications for earthquake studies and hydrocarbon exploration. Previous workers identified the key factors controlling the occurrence of both topographic modes and the related structural styles. Kinematic and stress boundary conditions are of first-order relevance. Surface mass transport and material properties affect fault network structure. Experiments demonstrate that dilatancy can generate positive topography even under simple-shear boundary conditions. Here, we use physical models with sand to show that the degree of compaction of the deformed rocks alone can determine the type of topography and related surface fault network structure in simple-shear settings. In our experiments, volume changes of ∼5% are sufficient to generate localized uplift or subsidence. We discuss scalability of model volume changes and fault network structure and show that our model fault zones satisfy geometrical similarity with natural flower structures. Our results imply that compaction may be an important factor in the development of topography and fault network structure along strike-slip faults in sedimentary basins.

[Book Review] Urban Maps : Instruments of Narrative and Interpretation in the City by Richard Brook and Nick Dunn, Ashgate, Farham, United Kingdom, 2011, 250pp. ISBN 978-0-754676-5-77.

Urban maps discusses new ways and tools to read and navigate the contemporary city. Each chapter investigates a possible approach to unravel the complexity of contemporary urban forms. Each tool is first defined, introducing its philosophical background, and is then discussed with case studies, showing its relevance for the navigation of the built environment. Urbanism classics such as the work of Lynch, Jacobs, Venuti and Scott-Brown, Lefebrve and Walter Benjamin are fundamental in setting the framework of the volume. In the introduction cities and mapping are first discussed, the former are illustrated as ‘a composite of invisible networks devoid of landmarks and overrun by nodes’ (p. 3), and ‘a series of unbounded spaces where mass production and mass consumption reproduce a standardised quasi-global culture’ (p. 6).