Solution structure and novel insights into the determinants of the receptor specificity of human relaxin-3

Relaxin- 3 is the most recently discovered member of the relaxin family of peptide hormones. In contrast to relaxin- 1 and - 2, whose main functions are associated with pregnancy, relaxin- 3 is involved in neuropeptide signaling in the brain. Here, we report the solution structure of human relaxin- 3, the first structure of a relaxin family member to be solved by NMR methods. Overall, relaxin- 3 adopts an insulin- like fold, but the structure differs crucially from the crystal structure of human relaxin- 2 near the B- chain terminus. In particular, the B- chain C terminus folds back, allowing Trp(B27) to interact with the hydrophobic-core. This interaction partly blocks the conserved RXXXRXXI motif identified as a determinant for the interaction with the relaxin receptor LGR7 and may account for the lower affinity of relaxin- 3 relative to relaxin for this receptor. This structural feature is likely important for the activation of its endogenous receptor, GPCR135.

The Expanded Human Kallikrein (KLK) gene family : genomic organisation, tissue specific expression and potential functions

The tissue kallikreins are serine proteases encoded by highly conserved multigene families. The rodent kallikrein (KLK) families are particularly large, consisting of 13 26 genes clustered in one chromosomal locus. It has been recently recognised that the human KLK gene family is of a similar size (15 genes) with the identification of another 12 related genes (KLK4-KLK15) within and adjacent to the original human KLK locus (KLK1-3) on chromosome 19q13.4. The structural organisation and size of these new genes is similar to that of other KLK genes except for additional exons encoding 5 or 3 untranslated regions. Moreover, many of these genes have multiple mRNA transcripts, a trait not observed with rodent genes. Unlike all other kallikreins, the KLK4-KLK15 encoded proteases are less related (25–44%) and do not contain a conventional kallikrein loop. Clusters of genes exhibit high prostatic (KLK2-4, KLK15) or pancreatic (KLK6-13) expression, suggesting evolutionary conservation of elements conferring tissue specificity. These genes are also expressed, to varying degrees, in a wider range of tissues suggesting a functional involvement of these newer human kallikrein proteases in a diverse range of physiological processes.

Evaluating sewage associated JCV and BKV polyomaviruses for sourcing human fecal pollution in a coastal river in Southeast Queensland Australia

In this study, the host-sensitivity and -specificity of JCV and BKV polyomaviruses were evaluated by testing wastewater/fecal samples from nine host groups in Southeast Queensland, Australia. The JCV and BKV polyomaviruses were detected in 48 human wastewater samples collected from the primary and secondary effluent suggesting high sensitivity of these viruses in human wastewater. Of the 81 animal wastewater/fecal samples tested, 80 were PCR negative for this marker. Only one sample from pig wastewater was positive. Nonetheless, the overall host-specificity of these viruses to differentiate between human and animal wastewater/fecal samples was 0.99. To our knowledge, this is the first study in Australia that reports the high specificity of JCV and BKV polyomaviruses. To evaluate the field application of these viruses to detect human fecal pollution, 20 environmental samples were collected from a coastal river. Of the 20 samples tested, 15% and 70% samples exceeded the regulatory guidelines for E. coli and enterococci levels for marine waters. In all, 5 (25%) samples were PCR positive for JCV and BKV indicated the presence of human fecal pollution in the studied river. The results suggest that JCV and BKV detection using PCR could be a useful tool for the identification of human sourced fecal pollution in coastal waters.

Modelling and execution of asset management process via workflow automation

An Asset Management (AM) life-cycle constitutes a set of processes that align with the development, operation and maintenance of assets, in order to meet the desired requirements and objectives of the stake holders of the business. The scope of AM is often broad within an organization due to the interactions between its internal elements such as human resources, finance, technology, engineering operation, information technology and management, as well as external elements such as governance and environment. Due to the complexity of the AM processes, it has been proposed that in order to optimize asset management activities, process modelling initiatives should be adopted. Although organisations adopt AM principles and carry out AM initiatives, most do not document or model their AM processes, let alone enacting their processes (semi-) automatically using a computer-supported system. There is currently a lack of knowledge describing how to model AM processes through a methodical and suitable manner so that the processes are streamlines and optimized and are ready for deployment in a computerised way. This research aims to overcome this deficiency by developing an approach that will aid organisations in constructing AM process models quickly and systematically whilst using the most appropriate techniques, such as workflow technology. Currently, there is a wealth of information within the individual domains of AM and workflow. Both fields are gaining significant popularity in many industries thus fuelling the need for research in exploring the possible benefits of their cross-disciplinary applications. This research is thus inspired to investigate these two domains to exploit the application of workflow to modelling and execution of AM processes. Specifically, it will investigate appropriate methodologies in applying workflow techniques to AM frameworks. One of the benefits of applying workflow models to AM processes is to adapt and enable both ad-hoc and evolutionary changes over time. In addition, this can automate an AM process as well as to support the coordination and collaboration of people that are involved in carrying out the process. A workflow management system (WFMS) can be used to support the design and enactment (i.e. execution) of processes and cope with changes that occur to the process during the enactment. So far few literatures can be found in documenting a systematic approach to modelling the characteristics of AM processes. In order to obtain a workflow model for AM processes commonalities and differences between different AM processes need to be identified. This is the fundamental step in developing a conscientious workflow model for AM processes. Therefore, the first stage of this research focuses on identifying the characteristics of AM processes, especially AM decision making processes. The second stage is to review a number of contemporary workflow techniques and choose a suitable technique for application to AM decision making processes. The third stage is to develop an intermediate ameliorated AM decision process definition that improves the current process description and is ready for modelling using the workflow language selected in the previous stage. All these lead to the fourth stage where a workflow model for an AM decision making process is developed. The process model is then deployed (semi-) automatically in a state-of-the-art WFMS demonstrating the benefits of applying workflow technology to the domain of AM. Given that the information in the AM decision making process is captured at an abstract level within the scope of this work, the deployed process model can be used as an executable guideline for carrying out an AM decision process in practice. Moreover, it can be used as a vanilla system that, once being incorporated with rich information from a specific AM decision making process (e.g. in the case of a building construction or a power plant maintenance), is able to support the automation of such a process in a more elaborated way.

Human and bovine adenoviruses for the detection of source-specific fecal pollution in coastal waters in Australia

In this study, the host-specificity and -sensitivity of human- and bovine-specific adenoviruses (HS-AVs and BS-AVs) were evaluated by testing wastewater/fecal samples from various animal species in Southeast, Queensland, Australia. The overall specificity and sensitivity of the HS-AVs marker were 1.0 and 0.78, respectively. These figures for the BS-AVs were 1.0 and 0.73, respectively. Twenty environmental water samples were colleted during wet conditions and 20 samples were colleted during dry conditions from the Maroochy Coastal River and tested for the presence of fecal indicator bacteria (FIB), host-specific viral markers, zoonotic bacterial and protozoan pathogens using PCR/qPCR. The concentrations of FIB in water samples collected after wet conditions were generally higher compared to dry conditions. HS-AVs was detected in 20% water samples colleted during wet conditions and whereas BS-AVs was detected in both wet (i.e., 10%) and dry (i.e., 10%) conditions. Both, C. jejuni mapA and Salmonella invA genes were detected in 10% and 10% of samples, respectively collected during dry conditions. The concentrations of Salmonella invA ranged between 3.5 × 102 to 4.3 × 102 genomic copies per 500 ml of water G. lamblia β-giardin gene was detected only in one sample (5%) collected during the dry conditions. Weak or significant correlations were observed between FIB with viral markers and zoonotic pathogens. However, during dry conditions, no significant correlations were observed between FIB concentrations with viral markers and zoonotic pathogens. The prevalence of HS-AVs in samples collected from the study river suggests that the quality of water is affected by human fecal pollution and as well as bovine fecal pollution. The results suggest that HS-AVs and BS-AVs detection using PCR could be a useful tool for the identification of human sourced fecal pollution in coastal waters.

Asset identification : addressing the climate change in public asset management process

Climate change is becoming increasingly apparent that is largely caused by human activities such as asset management processes, from planning to disposal, of property and infrastructure. One essential component of asset management process is asset identification. The aims of the study are to identify the information needed in asset identification and inventory as one of public asset management process in addressing the climate change issue; and to examine its deliverability in developing countries’ local governments. In order to achieve its aims, this study employs a case study in Indonesia. This study only discusses one medium size provincial government in Indonesia. The information is gathered through interviews of the local government representatives in South Sulawesi Province, Indonesia and document analysis provided by interview participants. The study found that for local government, improving the system in managing their assets is one of emerging biggest challenge. Having the right information in the right place and at the right time are critical factors in response to this challenge. Therefore, asset identification as the frontline step in public asset management system is holding an important and critical role. Furthermore, an asset identification system should be developed to support the mainstream of adaptation to climate change vulnerability and to help local government officers to be environmentally sensitive. Finally, findings from this study provide useful input for the policy makers, scholars and asset management practitioners to develop an asset inventory system as a part of public asset management process in addressing the climate change.

The application of public asset management in Indonesian local government : a case study in South Sulawesi Province

Purpose To identify the challenges faced by local government in Indonesia when adopting a Public Asset Management Framework. Design A Case Study in South Sulawesi Provincial Government was used as the approach to achieving the research objective. The case study involved two data collection techniques - interviews and document analysis. Findings The result of the study indicates there are significant challenges that the Indonesian local government need to manage when adopting a public asset management framework. Those challenges are: absence of an institutional and legal framework to support the asset management application; non-profit principle of public assets; multiple jurisdictions involved in the public asset management processes; the complexity of local government objectives; unavailability of data for managing public property; and limited human resources. Research Limitation This research is limited to one case study. It is a preliminary study from larger research that uses multiple case studies. The main research also investigates opportunities for local government by adopting and implementing public asset management. Originality/Value Findings from this study provide useful input for the policy makers, academics and asset management practitioners in Indonesia to establish a public asset management framework resulting in efficient and effective organizations, as well as an increase of public services quality. This study has a potential application for other developing countries.

Corneal confocal microscopy : a novel noninvasive test to diagnose and stratify the severity of human diabetic neuropathy

OBJECTIVE: The accurate quantification of human diabetic neuropathy is important to define at-risk patients, anticipate deterioration, and assess new therapies. ---------- RESEARCH DESIGN AND METHODS: A total of 101 diabetic patients and 17 age-matched control subjects underwent neurological evaluation, neurophysiology tests, quantitative sensory testing, and evaluation of corneal sensation and corneal nerve morphology using corneal confocal microscopy (CCM). ---------- RESULTS: Corneal sensation decreased significantly (P = 0.0001) with increasing neuropathic severity and correlated with the neuropathy disability score (NDS) (r = 0.441, P < 0.0001). Corneal nerve fiber density (NFD) (P < 0.0001), nerve fiber length (NFL), (P < 0.0001), and nerve branch density (NBD) (P < 0.0001) decreased significantly with increasing neuropathic severity and correlated with NDS (NFD r = −0.475, P < 0.0001; NBD r = −0.511, P < 0.0001; and NFL r = −0.581, P < 0.0001). NBD and NFL demonstrated a significant and progressive reduction with worsening heat pain thresholds (P = 0.01). Receiver operating characteristic curve analysis for the diagnosis of neuropathy (NDS >3) defined an NFD of <27.8/mm2 with a sensitivity of 0.82 (95% CI 0.68–0.92) and specificity of 0.52 (0.40–0.64) and for detecting patients at risk of foot ulceration (NDS >6) defined a NFD cutoff of <20.8/mm2 with a sensitivity of 0.71 (0.42–0.92) and specificity of 0.64 (0.54–0.74). ---------- CONCLUSIONS: CCM is a noninvasive clinical technique that may be used to detect early nerve damage and stratify diabetic patients with increasing neuropathic severity. Established diabetic neuropathy leads to pain and foot ulceration. Detecting neuropathy early may allow intervention with treatments to slow or reverse this condition (1). Recent studies suggested that small unmyelinated C-fibers are damaged early in diabetic neuropathy (2–4) but can only be detected using invasive procedures such as sural nerve biopsy (4,5) or skin-punch biopsy (6–8). Our studies have shown that corneal confocal microscopy (CCM) can identify early small nerve fiber damage and accurately quantify the severity of diabetic neuropathy (9–11). We have also shown that CCM relates to intraepidermal nerve fiber loss (12) and a reduction in corneal sensitivity (13) and detects early nerve fiber regeneration after pancreas transplantation (14). Recently we have also shown that CCM detects nerve fiber damage in patients with Fabry disease (15) and idiopathic small fiber neuropathy (16) when results of electrophysiology tests and quantitative sensory testing (QST) are normal. In this study we assessed corneal sensitivity and corneal nerve morphology using CCM in diabetic patients stratified for the severity of diabetic neuropathy using neurological evaluation, electrophysiology tests, and QST. This enabled us to compare CCM and corneal esthesiometry with established tests of diabetic neuropathy and define their sensitivity and specificity to detect diabetic patients with early neuropathy and those at risk of foot ulceration.

An exploration of the professional competencies required in engineering asset management

Engineering asset management (EAM) is a rapidly growing and developing field. However, efforts to select and develop engineers in this area are complicated by our lack of understanding of the full range of competencies required to perform. This exploratory study sought to clarify and categorise the professional competencies required of individuals at different hierarchical levels within EAM. Data from 14 interviews and 61 on-line survey participants has informed the development of an initial Professional Competency Framework. The nine competency categories indicate that Engineers working in this field need to be able to collaborate and influence others, complete objectives within organizational guidelines and be able to manage themselves effectively. Limitations and potential uses in practice and research for this framework are discussed.

In vitro primary cell culture as a physiologically relevant method for preclinical testing of human oncolytic adenovirus

Ad[I/PPT-E1A] is an oncolytic adenovirus that specifically kills prostate cells via restricted replication by a prostate-specific regulatory element. Off-target replication of oncolytic adenoviruses would have serious clinical consequences. As a proposed ex vivo test, we describe the assessment of the specificity of Ad[I/PPT-E1A] viral cytotoxicity and replication in human nonprostate primary cells. Four primary nonprostate cell types were selected to mimic the effects of potential in vivo exposure to Ad[I/PPT-E1A] virus: bronchial epithelial cells, urothelial cells, vascular endothelial cells, and hepatocytes. Primary cells were analyzed for Ad[I/PPT-E1A] viral cytotoxicity in MTS assays, and viral replication was determined by hexon titer immunostaining assays to quantify viral hexon protein. The results revealed that at an extreme multiplicity of infection of 500, unlikely to be achieved in vivo, Ad[I/PPT-E1A] virus showed no significant cytotoxic effects in the nonprostate primary cell types apart from the hepatocytes. Transmission electron microscopy studies revealed high levels of Ad[I/PPT-E1A] sequestered in the cytoplasm of these cells. Adenoviral green fluorescent protein reporter studies showed no evidence for nuclear localization, suggesting that the cytotoxic effects of Ad[I/PPT-E1A] in human primary hepatocytes are related to viral sequestration. Also, hepatocytes had increased amounts of coxsackie adenovirus receptor surface protein. Active viral replication was only observed in the permissive primary prostate cells and LNCaP prostate cell line, and was not evident in any of the other nonprostate cells types tested, confirming the specificity of Ad[I/PPT-E1A]. Thus, using a relevant panel of primary human cells provides a convenient and alternative preclinical assay for examining the specificity of conditionally replicating oncolytic adenoviruses in vivo.

State asset management reform in Indonesia : a wicked problem

Efficient state asset management is crucial for government departments that rely on the operations of their state assets in order to fulfil their public functions, which include public service provision and others. These assets may be expensive, extensive and or, complex, and can have a major impact on the ability of governments to perform its function over extended periods. Various governments around the world have increasingly recognised the importance of an efficient state asset management laws, policies, and practices; exemplified by the surge in state asset management reform. This phenomenon is evident in Indonesia, in particular through the establishment of the Directorate General of State Assets in 2006, who was appointed as the ultimate state asset manager (of Republic of Indonesia) and the proprietor of state asset management reform. The Directorate General of State Assets too has pledged its adherence to good governance principles within its state asset management laws and policies reform. However the degree that good governance principles are conceptualised is unknown, resulting in questions of how and to what extent is good governance principles evident within Indonesia's reformed state asset management laws and policies. This study seeks to understand the level of which good governance principles are conceptualised and understood within reformed state asset management policies in Indonesia (as a case study), and identify the variables that play a role in the implementation of said reform. Although good governance improvements has been a central tenet in Indonesian government agenda, and state asset management reform has propelled in priority due to found neglect and unfavourable audit results; there is ambiguity in regards to the extent that good governance is conceptualised within the reform, how and whether this relationship is understood by state asset managers (i.e government officials), and what (and how) other variables play a supporting and/or impeding role in the reform. Using empirical data involving a sample of four Indonesian regional governments and 70 interviews; discrepancy in which good governance principles are conceptualised, the level it is conceptualised, at which stage of state asset management practice it is conceptualised, and the level it is understood by state asset managers (i.e government officials) was found. Human resource capacity and capability, the notion of 'needing more time', low legality, infancy of reform, and dysfunctional sense of stewardship are identified as specific impeding variables to state asset management reform; whilst decentralisation and regional autonomy regime, political history, and culture play a consistent undercurrent key role in good governance related reforms within Indonesia. This study offers insights to Indonesian policy makers interested in ensuring the conceptualisation and full implementation of good governance in all areas of governing, particularly within state asset management practices. Most importantly, this study identifies an asymmetry in good governance understanding, perspective, and assumptions between policy maker (i.e high level government officials) and policy implementers (i.e low level government officials); to be taken into account for future policy evolvements and/or writing. As such, this study suggests the need for a modified perspective and approach to good governance conceptualisation and implementation strategies, one that acknowledges and incorporates a nation's unique characteristics and no longer denies the double-edged sword of simplified assumptions of governance.

A public asset management framework for Indonesian local governments

The decentralisation reform in Indonesia has mandated the Central Government to transfer some functions and responsibilities to local governments including the transfer of human resources, assets and budgets. Local governments became giant asset holders almost overnight and most were ill prepared to handle these transformations. Assets were transferred without analysing local government need, ability or capability to manage the assets and no local government was provided with an asset management framework. Therefore, the aim of this research is to develop a Public Asset Management Framework for provincial governments in Indonesia, especially for infrastructure and real property assets. This framework will enable provincial governments to develop integrated asset management procedures throughout asset‘s lifecycle. Achieving the research aim means answering the following three research questions; 1) How do provincial governments in Indonesia currently manage their public assets? 2) What factors influence the provincial governments in managing these public assets? 3) How is a Public Asset Management Framework developed that is specific for the Indonesian provincial governments‘ situation? This research applied case studies approach after a literature review; document retrieval, interviews and observations were collated. Data was collected in June 2009 (preliminary data collection) and January to July 2010 in the major eastern Indonesian provinces. Once the public asset management framework was developed, a focus group was used to verify the framework. Results are threefold and indicate that Indonesian provincial governments need to improve the effectiveness and efficiency of current practice of public asset management in order to improve public service quality. The second result shows that the 5 major concerns that influence the local government public asset management processes are asset identification and inventory systems, public asset holding, asset guidance and legal arrangements, asset management efficiency and effectiveness, and, human resources and their organisational arrangements. The framework was then applied to assets already transferred to local governments and so included a system of asset identification and a needs analysis to classify the importance of these assets to local governments, their functions and responsibilities in delivering public services. Assets that support local government functions and responsibilities will then be managed using suitable asset lifecycle processes. Those categorised as surplus assets should be disposed. Additionally functions and responsibilities that do not need an asset solution should be performed directly by local governments. These processes must be measured using performance measurement indicators. All these stages should be guided and regulated with sufficient laws and regulations. Constant improvements to the quality and quantity of human resources hold an important role in successful public asset management processes. This research focuses on developing countries, and contributes toward the knowledge of a Public Asset Management Framework at local government level, particularly Indonesia. The framework provides local governments a foundation to improve their effectiveness and efficiency in managing public assets, which could lead to improved public service quality. This framework will ensure that the best decisions are made throughout asset decision ownership and provide a better asset life cycle process, leading to selection of the most appropriate asset, improve its acquisition and delivery process, optimise asset performance, and provide an appropriate disposal program.

Towards an integrated maturity model of asset management capabilities

Asset service organisations often recognize asset management as a core competence to deliver benefits to their business. But how do organizations know whether their asset management processes are adequate? Asset management maturity models, which combine best practices and competencies, provide a useful approach to test the capacity of organisations to manage their assets. Asset management frameworks are required to meet the dynamic challenges of managing assets in contemporary society. Although existing models are subject to wide variations in their implementation and sophistication, they also display a distinct weakness in that they tend to focus primarily on the operational and technical level and neglect the levels of strategy, policy and governance as well as the social and human resources – the people elements. Moreover, asset management maturity models have to respond to the external environmental factors, including such as climate change and sustainability, stakeholders and community demand management. Drawing on five dimensions of effective asset management – spatial, temporal, organisational, statistical, and evaluation – as identified by Amadi Echendu et al. [1], this paper carries out a comprehensive comparative analysis of six existing maturity models to identify the gaps in key process areas. Results suggest incorporating these into an integrated approach to assess the maturity of asset-intensive organizations. It is contended that the adoption of an integrated asset management maturity model will enhance effective and efficient delivery of services.