The molecular basis for selective inhibition of unconventional mRNA splicing by an IRE1-binding small molecule

IRE1 couples endoplasmic reticulum unfolded protein load to RNA cleavage events that culminate in the sequence-specific splicing of the Xbp1 mRNA and in the regulated degradation of diverse membrane-bound mRNAs. We report on the identification of a small molecule inhibitor that attains its selectivity by forming an unusually stable Schiff base with lysine 907 in the IRE1 endonuclease domain, explained by solvent inaccessibility of the imine bond in the enzyme-inhibitor complex. The inhibitor (abbreviated 4μ8C) blocks substrate access to the active site of IRE1 and selectively inactivates both Xbp1 splicing and IRE1-mediated mRNA degradation. Surprisingly, inhibition of IRE1 endonuclease activity does not sensitize cells to the consequences of acute endoplasmic reticulum stress, but rather interferes with the expansion of secretory capacity. Thus, the chemical reactivity and sterics of a unique residue in the endonuclease active site of IRE1 can be exploited by selective inhibitors to interfere with protein secretion in pathological settings.

Rethinking sustainable urban development: Towards an integrated planning and development process

A city is the most dramatic manifestation of human activities on the environment. This human dominated organism degrades natural habitats, simplifies species composition, disrupts hydrological systems, and modifies energy flow and nutrient cycling. Sustainable urban development is seen as a panacea to minimise these externalities caused by widespread human activities on the environment. The concept of sustainable urban development has been around over a considerably long-time as the need to adopt environmentally sustainable behaviours made the international community commit to it. However, to date such development has not been achieved in large scales anywhere around the globe. This review paper aims to look at the sustainable urban development concept from the lens of planning and development integration to generate new insights and directions. The paper reports the outcome of the review of the literature on planning and development approaches—i.e., urban planning, ecological planning, urban development, sustainable urban development—and proposes a new process to support the efforts for achieving sustainable urban development—i.e., integrated urban planning and development process. The findings of this review paper highlights that adopting such holistic planning and development process generate a potential to further support the progress towards achieving sustainability agendas of our cities.

Putting people in planning: participatory democracy, community building and social inclusion

Like other Western nations, since the nineteenth century Australia has been a representative democracy, in which citizens elect parliamentary representatives to make decisions and develop policies on their behalf (see chapter 5). These representatives are supported in their decision making by an ‘arm’s-length’, ‘techno-bureaucratic administration’, which includes experts such as environmental planners (Fung and Wright 2003, p. 3). However, as the issues for decision-making become increasingly complex, and societies increasingly diverse, the idea of citizen participation in decision-making is ever more accepted. There is now a significant body of political theory arguing for a more participatory model of democracy (participatory democracy), a model that strives to create opportunities for all members of a society to contribute meaningfully to decisions about the matters affecting their lives.

Use and usefulnss of PDSs in the financial planning context

Following considerable criticism of the complexity and lack of readability of product disclosure statements (PDSs), regulatory changes were introduced requiring shorter PDSs for certain investment products. This paper reports the findings of an online survey of financial planners regarding use of managed investment scheme (MIS) PDSs with clients, the perceived usefulness of PDSs as an information source, and their views on shorter PDSs. Our findings highlight major concerns about the usefulness of the PDS and disclosure reforms.

Footprints to pathways : reconciliation action planning in industry to sustain Indigenous employment in Queensland

This paper provides an introductory discussion to a study focusing on industry Reconciliation Action Plans (RAP) and sustaining Indigenous employment in Queensland. Indigenous people continue to experience deep and persistent disadvantage in employment, which limits their life prospects (McLachlan, Gilgillan & Gordon, 2013). A major contributing factor to this detriment is irregular employment and or unemployment. A reasonable standard of living has been found to be determined by access to economic resources such as income and wealth. Denial of this access, denies access to income streams, social status, and engagement in meaningful activities. Hence, job loss and joblessness are triggers of disadvantage (McLachlan, et al., 2013). For young Indigenous people, lack of access has lasting effects particularly if they have multiple characteristics that place them at risk of disadvantage. The project aims to develop knowledge and understanding of Industry RAPs mediate employment opportunities for Indigenous people and how young Indigenous people conceive of their employment options and the processes by which employers can best support Indigenous people. It adopts two theoretical frameworks to investigate the aim of the study : (1) Lave and Wenger’s (1991) theory of communities of practice and, (2) Sen’s (1993) capability approach which provides a structure for examining individual well-being in the context of societal inequality. This paper discusses the first research question of the study: What are Industry Reconciliation Action Plans? What is included in RAPs? Why do Industries develop RAPs? How do RAPs attract, recruit, retain, and tenure Indigenous people? The project’s significance rests with its focus on Industry, employers, policies and practices that aid the attraction and retention of Indigenous people in employment.

Transit Capacity and Quality of Service Manual (TCQSM) applications for education

Relevant Education Contexts, Examples of TCQSM Applicability to Undergraduate Disciplines, Why Teach with the TCQSM?, TCQS Teaching Tools, Theory Curriculum Example: Examination Question, Problem Based Learning Example: Senior Year Semester Team Project, Honors Dissertation Example Topics, Where to From Here?

How transit route passenger load and distance can together influence quality of service

This paper investigates: - correlation between transit route passenger loading and travel distance - its implications on quality of service (QoS) and resource productivity. It uses Automatic Fare Collection (AFC) data across a weekday on a premium bus line in Brisbane, Australia. A composite load-distance factor is proposed as a new measure for profiling transit route on-board passenger comfort QoS. Understanding these measures and their correlation is important for planning, design, and operational activities.

Optimal camera planning under versatile user constraints in multi-camera image processing systems

The selection of optimal camera configurations (camera locations, orientations, etc.) for multi-camera networks remains an unsolved problem. Previous approaches largely focus on proposing various objective functions to achieve different tasks. Most of them, however, do not generalize well to large scale networks. To tackle this, we propose a statistical framework of the problem as well as propose a trans-dimensional simulated annealing algorithm to effectively deal with it. We compare our approach with a state-of-the-art method based on binary integer programming (BIP) and show that our approach offers similar performance on small scale problems. However, we also demonstrate the capability of our approach in dealing with large scale problems and show that our approach produces better results than two alternative heuristics designed to deal with the scalability issue of BIP. Last, we show the versatility of our approach using a number of specific scenarios.

The effect of hypoxia on the stemness and differentiation capacity of PDLC and DPC

Introduction. Stem cells are regularly cultured under normoxic conditions. However, the physiological oxygen tension in the stem cell niche is known to be as low as 1-2% oxygen, suggesting that hypoxia has a distinct impact on stem cell maintenance. Periodontal ligament cells (PDLCs) and dental pulp cells (DPCs) are attractive candidates in dental tissue regeneration. It is of great interest to know whether hypoxia plays a role in maintaining the stemness and differentiation capacity of PDLCs and DPCs. Methods. PDLCs and DPCs were cultured either in normoxia (20% O2) or hypoxia (2% O2). Cell viability assays were performed and the expressions of pluripotency markers (Oct-4, Sox2, and c-Myc) were detected by qRT-PCR and western blotting. Mineralization, glycosaminoglycan (GAG) deposition, and lipid droplets formation were assessed by Alizarin red S, Safranin O, and Oil red O staining, respectively. Results. Hypoxia did not show negative effects on the proliferation of PDLCs and DPCs. The pluripotency markers and differentiation potentials of PDLCs and DPCs significantly increased in response to hypoxic environment. Conclusions. Our findings suggest that hypoxia plays an important role in maintaining the stemness and differentiation capacity of PDLCs and DPCs.

FixVegas : facilitating multi-directional communication between government officials and citizens to support urban planning in the city of Brisbane

The goal of this project was to develop a mobile application for the iOS platform, that would support the partner of this project, the Brisbane City Council, in stronger engage citizens in participating in urban planning and development projects. The resulting application is an extended version of FixVegas, a system that allows citizens to report maintenance request to the Brisbane City Council through their smartphone. The new version of the system makes all incoming requests publicly available within the application, allows users to support, comment or disapprove of these. As an addition, the concept of the idea has been introduced. Citizens can submit suggestions for improving the city to the municipality, discuss them with other fellow citizens and, ideally, also with Council representatives. The city officials as well are provided with the ability of publishing development project as an idea and let citizens deliberate it. This way, bidirectional communication between these two parties is created. A web interface complements the iPhone application. The system has been developed after the principle of User Centered Design, by assessing user needs, creating and evaluating prototypes and conducting a user study. The study showed that FixVegas2 has been perceived as an enhancement compared to the previous version, and that the idea concept has been received on a positive note. Indepth questions, such as the influence the system could have on community dynamics or the public participation in urban planning projects could only hardly investigated. However, these findings can be achieved by the alternative study designs that have been proposed.

A therapeutic approach to assessing legal capacity in Australia

Australia lacks a satisfactory, national paradigm for assessing legal capacity in the context of testamentary, enduring power of attorney and advance care directive documents. Capacity assessments are currently conducted on an ad hoc basis by legal and/or medical professionals. The reliability of the assessment process is subject to the skill set and mutual understanding of the legal and/or medical professional conducting the assessment. There is a growth in the prevalence of diseases such as dementia. Such diseases impact upon cognition which increasingly necessitates collaboration between the legal and medical professions when assessing the effect of mentally disabling conditions upon legal capacity. Miscommunication and lack of understanding between legal and medical professionals involved could impede the development of a satisfactory paradigm. This article will discuss legal capacity assessment in Australia and how to strengthen the relationship between legal and medical professionals involved in capacity assessments. The development of a national paradigm would promote consistency and transparency of process, helping to improve the professional relationship and maximising the principles of autonomy, participation and dignity.

Broadcasting digital stories on Australian community television : the Digistories Anthology

Community-based arts and media movements have been intsrumental in building population-wide creative capacity for cultural development, social participation and social transformation in many parts of the world. Digital storytelling is a form of media practice that was pioneered in the United States at the intersection of these movements. It is described here as a ‘co-creative’ media production method. This description aims to differentiate the approaches to collaborative content creation that are used in community cultural development (CCD) and community media movements from those valued in professional and consumer modes of media production. Yet, the products of co-creative practices, such as digital stories, do not circulate widely through existing media networks or through the newer social media networks that Australian CCD and community media movements anticipated by at least twenty years. The complex politics of story ownership are one of a number of factors that often render ‘publication’ a secondary consideration in the making of digital stories. The possibility of ‘downstream’ use and re-use of stories in other networks is not usually considered in initial planning and development processes. As landmark projects such as Capture Wales indicate, even where stories are made for broadcast outcomes, television can be a problematic window for exhibiting digital stories. Scepticism about the brave new world of reality television and user generated content also circulates in digital storytelling networks, especially when it comes to ethical concerns for managing the risks of harm associated with widespread distribution of digital stories to indiscriminate publics. This publication reports on a collaborative action research project that took a closer look at some of the constraints relating to the problems of re-purposing digital stories for television. It focussed on ‘best practice’ for managing the risks of harm to storytellers in the process of re-purposing digital stories for broadcast on community television.

Road safety knowledge exchange and capacity building between China and Australia

Road traffic injuries are one of the major public health burdens worldwide. The United Nations Decade of Action for Road Safety (2011-2020) implores all nations to work to reduce this burden. This decade represents a unique and historic period of time in the field of road safety. Information exchange and co-operation between nations is an important step in achieving the goal. The burden of road crashes, fatalities and injuries is not equally distributed. We know that low and middle-income countries experience the majority of the road trauma burden. Therefore it is imperative that these countries learn from the successes of others that have developed and implemented road safety laws, public education campaigns and countermeasures over many years and have achieved significant road trauma reductions as a result. China is one of the countries experiencing a large road trauma burden. Vulnerable road users such as pedestrians and cyclists make up a large proportion of fatalities and injuries in China. Speeding, impaired/drug driving, distracted driving, vehicle overloading, inadequate road infrastructure, limited use of safety restraints and helmets, and limited road safety training have all been identified as contributing to the problem. Some important steps have been taken to strengthen China’s approach, including increased penalties for drunk driving in May 2011 and increased attention to school bus safety in 2011/12. However, there is still a large amount of work needed to improve the current road safety position in China. This paper provides details of a program to assist with road safety knowledge exchange between China and Australia that was funded by the Australian Government which was undertaken in the latter part of 2012. The four month program provided the opportunity for the first author to work closely with key agencies in Australia that are responsible for policy development and implementation of a broad range of road safety initiatives. In doing so, an in-depth understanding was gained about key road safety strategies in Australia and processes for developing and implementing them. Insights were also gained into the mechanisms used for road safety policy development, implementation and evaluation in several Australian jurisdictions. Road traffic law and enforcement issues were explored with the relevant jurisdictional transport and police agencies to provide a greater understanding of how Chinese laws and practices could be enhanced. Working with agencies responsible for public education and awareness campaigns about road safety in Australia also provided relevant information about how to promote road safety at the broader community level in China. Finally, the program provided opportunities to work closely with several world-renowned Australian research centres and key expert researchers to enhance opportunities for ongoing road safety research in China. The overall program provided the opportunity for the first author to develop knowledge in key areas of road safety strategy development, implementation and management which are directly relevant to the current situation in China. This paper describes some main observations and findings from participation in the program.

Academic legal research and academic research capacity enhancement working topic : "purposes and objectives of law schools beyond educating students (research, capacity building,community service and outreach)"

One of the main objectives of law schools beyond educating students is to produce viable legal research. The comments in this paper are basically confined to the Australian context, and to examine this topic effectively, it is necessary to briefly review the current tertiary research agenda in Australia. This paper argues that there is a need for recognition and support for an expanded legal research framework along with additional research training for legal academics. There also needs to be more effective methods of measuring and recognising quality in legal research. This method needs to be one that can engender respect in an interdisciplinary context.