Contribution of transmembrane domain V amino acids to β1l-adrenoceptor activity and affinity

Introduction. There are two binding sites on the β1-adrenoceptor (AR), β1H and β1L corresponding to high and low affinity binding sites respectively, which can be activated to cause cardiostimulation. Some β-blockers that block β1AR and β2ARs can activate β1LARs at higher concentrations than those required to cause blockade. The β2AR does not form a corresponding low affinity binding site and therefore we postulated that heterologous amino acids are responsible for the formation of β1LAR. Aim. To investigate whether heterologous amino acids of transmembrane domain V (TMDV) of β1AR and β2ARs contribute to β1LAR. Methods. β1ARs, β2ARs and mutant β1ARs containing all (β1(β2TMDV)AR) or single amino acids of TMDV of the β2AR were prepared and stably expressed in Chinese Hamster Ovary cells. Concentration-effect curves for cyclicAMP accumulation were carried out for (-)-CGP12177 in the absence or presence of (-)-bupranolol. Results. The potencies (pEC50) of (-)-CGP12177 were β2AR (9.24 ± 0.14, n = 5), β1(V230I)AR (9.07 ± 0.07, n = 10), β1(β2TMDV)AR (8.86 ± 0.10, n = 15), β1(R222Q)AR (8.09 ± 0.29, n = 6), β1AR (8.00 ± 0.11, n = 11). The affinities (pKB) of (-)-bupranolol were β2AR (9.82 ± 0.52, n = 5), β1(V230I)AR (7.64 ± 0.12, n = 8), β1(β2TMV)AR (8.06 ± 0.17, n = 8), β1(R222Q)AR (7.33 ± 0.23, n = 5), β1AR (7.23 ± 0.23, n = 5). Discussion. The potency of (-)-CGP12177 was higher at β2AR than at β1AR consistent with activation through a low affinity site at the β1AR (β1LAR). The presence of V230 in β1AR accounted for the lower potency of (-)-CGP 12177. The affinity of (-)-bupranolol was lower at β1AR compared to β2AR. The presence of V230 in β1AR accounted in part for the lower affinity. In conclusion TMDV of the β1AR contributes in part to the low affinity binding site of β1AR.

Prospective bus rapid transit scenarios for pilot corridor in Dhaka

Dhaka doesn’t have a mature transport system. Lacking in institutional arrangements, policy and planning, and law enforcement, the transport system operates has developed ad hoc and is situationally problematic. Absence of proper coordination between modes, poor public transport system, inadequate pedestrian facilities, and environmental degradation justify full consideration of Bus Rapid Transit (BRT) in Dhaka. BRT centres on sustainable transport principles. BRT is a system, which is capable to mitigate Dhaka’s transport problem if properly planned. In Strategic transport plan of Dhaka three BRT transport corridor has been proposed and BRT pre-feasibility study came up with one pilot corridor for early implementation of BRT. This paper first reviews international best practices then explores various BRT system packages and evaluates the suitability of these BRT packages by analyzing current bus service condition and physical and geometric configuration along the BRT pilot corridor. It concludes by proposing some BRT scenarios, which can be considered for further evaluation with respect to speed, delay, travel time and environmental pollution.

A model for constraint and delegation management

This paper introduces a model to facilitate delegation, including ad-hoc delegation, in cross security domain activities. Specifically, this paper proposes a novel delegation constraint management model to manage and track delegation constraints across security domains. An algorithm to trace the authority of delegation constraints is introduced as well as an algorithm to form a delegation constraint set and detect/prevent potential conflicts. The algorithms and the management model are built upon a set of formal definitions of delegation constraints.

Spatial stimulus : Model making in the architectural design studio

This action research examines the enhancement of visual communication within the architectural design studio through physical model making. „It is through physical model making that designers explore their conceptual ideas and develop the creation and understanding of space,‟ (Salama & Wilkinson 2007:126). This research supplements Crowther‟s findings extending the understanding of visual dialogue to include physical models. „Architecture Design 8‟ is the final core design unit at QUT in the fourth year of the Bachelor of Design Architecture. At this stage it is essential that students have the ability to communicate their ideas in a comprehensive manner, relying on a combination of skill sets including drawing, physical model making, and computer modeling. Observations within this research indicates that students did not integrate the combination of the skill sets in the design process through the first half of the semester by focusing primarily on drawing and computer modeling. The challenge was to promote deeper learning through physical model making. This research addresses one of the primary reasons for the lack of physical model making, which was the limited assessment emphasis on the physical models. The unit was modified midway through the semester to better correlate the lecture theory with studio activities by incorporating a series of model making exercises conducted during the studio time. The outcome of each exercise was assessed. Tutors were surveyed regarding the model making activities and a focus group was conducted to obtain formal feedback from students. Students and tutors recognised the added value in communicating design ideas through physical forms and model making. The studio environment was invigorated by the enhanced learning outcomes of the students who participated in the model making exercises. The conclusions of this research will guide the structure of the upcoming iteration of the fourth year design unit.

Design of a model-generated repository as a service for USDL

SAP and its research partners have been developing a lan- guage for describing details of Services from various view- points called the Unified Service Description Language (USDL). At the time of writing, version 3.0 describes technical implementation aspects of services, as well as stakeholders, pricing, lifecycle, and availability. Work is also underway to address other business and legal aspects of services. This language is designed to be used in service portfolio management, with a repository of service descriptions being available to various stakeholders in an organisation to allow for service prioritisation, development, deployment and lifecycle management. The structure of the USDL metadata is specified using an object-oriented metamodel that conforms to UML, MOF and EMF Ecore. As such it is amenable to code gener-ation for implementations of repositories that store service description instances. Although Web services toolkits can be used to make these programming language objects available as a set of Web services, the practicalities of writing dis- tributed clients against over one hundred class definitions, containing several hundred attributes, will make for very large WSDL interfaces and highly inefficient “chatty” implementations. This paper gives the high-level design for a completely model-generated repository for any version of USDL (or any other data-only metamodel), which uses the Eclipse Modelling Framework’s Java code generation, along with several open source plugins to create a robust, transactional repository running in a Java application with a relational datastore. However, the repository exposes a generated WSDL interface at a coarse granularity, suitable for distributed client code and user-interface creation. It uses heuristics to drive code generation to bridge between the Web service and EMF granularities.

Development of an autonomous helicopter for aerial powerline inspections

Autonomous mini-helicopters have been seen as a viable option for aerial-based powerline inspections, however there are numerous research and engineering challenges in developing a system capable of achieving this task in a dependable manner. We have developed an autonomous helicopter as a research platform which will allow us to demonstrate proof-of-concept capabilities for powerline inspections. Through numerous development cycles and from flight test experience we have gained insights into the key challenges in this area. We discuss these insights, describe the helicopter platform and present our research progress in the area of obstacle avoidance for mini-helicopters.

Whole life cycle costing for Malaysia residential property development : the cultural environment

As knowledge of the residential development costing impact on resource and budgeting use increase, developers are moving towards more sustainable solution by implementing whole life cycle costing. Property management requires an understanding of infrastructure management, service life planning and quality management. Today, people are beginning to realize that effective property management in high-rise residential property can sustain the property value and maintain high returns on their investment. The continuous growth of high-rise residential properties indicates that there is a need for an effective property management system to provide a sustainable high-rise residential property development. For such reasons, this paper attempts to study the culture that have been applied due the residential property development in Malaysia as to improve to the best and sustainable practice in providing the best cost effectiveness management system in residential property development.

Linking the American Time Use Survey (ATUS) and the Compendium of Physical Activities : methods and rationale

Background: The 2003 Bureau of Labor Statistics American Time Use Survey (ATUS) contains 438 distinct primary activity variables that can be analyzed with regard to how time is spent by Americans. The Compendium of Physical Activities is used to code physical activities derived from various surveys, logs, diaries, etc to facilitate comparison of coded intensity levels across studies. ------ ----- Methods: This paper describes the methods, challenges, and rationale for linking Compendium estimates of physical activity intensity (METs, metabolic equivalents) with all activities reported in the 2003 ATUS. ----- ----- Results: The assigned ATUS intensity levels are not intended to compute the energy costs of physical activity in individuals. Instead, they are intended to be used to identify time spent in activities broadly classified by type and intensity. This function will complement public health surveillance systems and aid in policy and health-promotion activities. For example, at least one of the future projects of this process is the descriptive epidemiology of time spent in common physical activity intensity categories. ----- ----- Conclusions: The process of metabolic coding of the ATUS by linking it with the Compendium of Physical Activities can make important contributions to our understanding of Americans’ time spent in health-related physical activity.

Limitations and challenges in MSC delivery for bone regeneration

Objective: Regeneration of osseous defects by tissue-engineering or cell delivery approach provides a novel means of treatment utilizing cell biology, materials sciences, and molecular biology. The concept of in vitro explanted mesenchymal stem cells (MSCs) with an ability to induce new bone formation has been demonstrated in some small animal models. However, contradictory results have been reported regarding the regenerative capacity of MSCs after ex vivo expansion due to the lack of the understanding of microenvironment for MSC differentiation in vivo. ----- ----- Methods: In our laboratory tissue-derived and bone marrow-derived MSCs have been investigated in their osteogenesis. Cell morphology and proliferation were studied by microscopy, confocal microscopy, FACS and cell counting. Cell differentiation and matrix formation were analysed by matrix staining, quantitative PCR, and immunohistochemistry. A SCID skull defect model was used for cell transplantation studies.----- ----- Results: It was noted that tissue-derived and bone marrow-derived MSCs showed similar characteristics in cell surface marker expression, mesenchymal lineage differentiation potential, and cell population doubling. MSCs from both sources could initiate new bone formation in bone defects after delivery into a critical size defects. The bone forming cells were from both transplanted cells and endogenous cells from the host. Interestingly, the majority of in vitro osteogenic differentiated cells did not form new bone directly even though mineralized matrix was synthesized in vitro by MSCs. Furthermore, no new bone formation was detected when MSCs were transplanted subcutaneously.----- ----- Conclusion: This study unveiled the limitations of MSC delivery in bone regeneration and proposed that in vivo microenvironment needs to be optimized for MSC delivery in osteogenesis.

Integrated literacies : every online player wins a prize

QUT Library’s model of learning support brings together academic literacy (study skills) and information literacy (research skills). The blended portfolio enables holistic planning and development, seamless services, connected learning resources and more authentic curriculum-embedded education. The model reinforces the Library’s strategic focus on learning service innovation and active engagement in teaching and learning. ----- ----- ----- The online learning strategy is a critical component of the broader literacies framework. This strategy unifies new and existing online resources (e.g.: Pilot, QUT cite|write and IFN001|AIRS Online) to augment learner capability. Across the suite, prudent application of emerging technologies with visual communications and learning design delivers a wide range of adaptive study tools. Separately and together, these resources meet the learning needs and styles of a diverse cohort providing positive and individual learning opportunities. Deliberate articulation with strategic directions regarding First Year Experience, assessment, retention and curriculum alignment assures that the Library’s initiatives move in step with institutional objectives relating to enhancing the student experience and flexible blended learning. ----- ----- ----- The release of Studywell in 2010 emphasises the continuing commitment to blended literacy education. Targeting undergraduate learners (particularly 1st year/transition), this online environment provides 24/7 access to practical study and research tools. Studywell’s design and application of technology creates a “discovery infrastructure” [1] which facilitates greater self-directed learning and interaction with content. ----- ----- ----- This paper presents QUT Library’s online learning strategy within the context of the parent “integrated literacies” framework. Highlighting the key online learning resources, the paper describes the inter-relationships between those resources to develop complementary literacies. The paper details broad aspects of the overarching learning and study support framework as well as the online strategy, including strategic positioning, quality and evaluation processes, maintenance, development, implementation, and client engagement and satisfaction with the learning resources.

Extending constructability concept to include operation and maintenance issues

The concept of constructability uses integration art of individual functions through a valuable and timely construction inputs into planning and design development stages. It results in significant savings in cost and time needed to finalize infrastructure projects. However, available constructability principles, developed by CII Australia (1993), do not cover Operation and Maintenance (O&M) phases of projects, whilst major cost and time in multifaceted infrastructure projects are spent in post-occupancy stages. This paper discusses the need to extend the constructability concept by examining current O&M issues in the provision of multifaceted building projects. It highlights available O&M problems and shortcomings of building projects, as well as their causes and reasons in different categories. This initial categorization is an efficient start point for testing probable present O&M issues in various cases of complex infrastructure building projects. This preliminary categorization serve as a benchmark to develop an extended constructability model that considers the whole project life cycle phases rather than a specific phase. It anticipates that the development of an extended constructability model can reduce significant number of reworks, mistakes, extra costs and time wasted during delivery stages of multifaceted building projects.

Evaluating the influences of stakeholder management on construction project quality

The issue of ensuring that construction projects achieve high quality outcomes continues to be an important consideration for key project stakeholders. Although a lot of quality practices have been done within the industry, establishment and achievement of reasonable levels of quality in construction projects continues to be a problem. While some studies into the introduction and development of quality practices and stakeholder management in the construction industry have been undertaken separately, no major studies have so far been completed that examine in depth how quality management practices that specifically address stakeholders’ perspectives of quality can be utilised to contribute to the ultimate constructed quality of projects. This paper encompasses and summarizes a review of the literature related to previous research undertaken on quality within the industry, focuses on the benefits and shortcomings, together with examining the concept of integrating stakeholder perspectives of project quality for improvement of outcomes throughout the project lifecycle. Findings discussed in this paper reveal a pressing need for investigation, development and testing of a framework to facilitate better implementation of quality management practices and thus achievement of better quality outcomes within the construction industry. The framework will incorporate and integrate the views of stakeholders on what constitutes final project quality to be utilised in developing better quality management planning and systems aimed ultimately at achieving better project quality delivery.

An assessment of timber dwellings typical of the Queenslander era, and constraints associated with their relocation, component and adaptive reuse when considering 'regeneration'

This paper presents an explanation of why the reuse of building components after demolition or deconstruction is critical to the future of the construction industry. An examination of the historical cause and response to climate change sets the scene as to why governance is becoming increasingly focused on the built environment as a mechanism to controlling waste generation associated with the process of demolition, construction and operation. Through an annotated description to the evolving design and construction methodology of a range of timber dwellings (typically 'Queenslanders' during the eras of 1880-1900, 1900-1920 & 1920-1940) the paper offers an evaluation to the variety of materials, which can be used advantageously by those wishing to 'regenerate' a Queenslander. This analysis of 'regeneration' details the constraints when considering relocation and/ or reuse by adaption including deconstruction of building components against the legislative framework requirements of the Queensland Building Act 1975 and the Queensland Sustainable Planning Act 2009, with a specific examination to those of the Building Codes of Australia. The paper concludes with a discussion of these constraints, their impacts on 'regeneration' and the need for further research to seek greater understanding of the practicalities and drivers of relocation, adaptive and building components suitability for reuse after deconstruction.

Safety leaders' perceptions of safety culture in a large Australian construction organisation

Safety culture in the construction industry is a growing research area. The unique nature of construction industry works – being project-based, varying in size and focus, and relying on a highly transient subcontractor workforce – means that safety culture initiatives cannot be easily translated from other industries. This paper reports on the first study in a three year collaborative industry and university research project focusing on safety culture practices and development in one of Australia’s largest global construction organisations. The first round of a modified Delphi method is reported, and describes the insights gained from 41 safety leaders’ perceptions and understandings of safety culture within the organisation. In-depth, semi-structured interviews were conducted, and will be followed by a quantitative perception survey with the same sample. Participants included Senior Executives, Corporate Managers, Project Managers, Safety Managers and Site Supervisors. Leaders’ definitions and descriptions of safety culture were primarily action-oriented and some confusion was evident due to the sometimes implicit nature of culture in organisations. Leadership was identified as a key factor for positive safety culture in the organisation, and there was an emphasis on leaders demonstrating commitment to safety, and being visible to the project-based workforce. Barriers to safety culture improvement were also identified, with managers raising diverse issues such as the transient subcontractor workforce and the challenge of maintaining safety as a priority in the absence of safety incidents, under high production pressures. This research is unique in that it derived safety culture descriptions from key stakeholders within the organisation, as opposed to imposing traditional conceptualisations of safety culture that are not customised for the organisation or the construction industry more broadly. This study forms the foundation for integrating safety culture theory and practice in the construction industry, and will be extended upon in future studies within the research program.