Gravity-driven fingering simulations for a thin liquid film flowing down the outside of a vertical cylinder

A numerical study is presented to examine the fingering instability of a gravity-driven thin liquid film flowing down the outer wall of a vertical cylinder. The lubrication approximation is employed to derive an evolution equation for the height of the film, which is dependent on a single parameter, the dimensionless cylinder radius. This equation is identified as a special case of that which describes thin film flow down an inclined plane. Fully three-dimensional simulations of the film depict a fingering pattern at the advancing contact line. We find the number of fingers observed in our simulations to be in excellent agreement with experimental observations and a linear stability analysis reported recently by Smolka & SeGall (Phys Fluids 23, 092103 (2011)). As the radius of the cylinder decreases, the modes of perturbation have an increased growth rate, thus increasing cylinder curvature partially acts to encourage the contact line instability. In direct competition with this behaviour, a decrease in cylinder radius means that fewer fingers are able to form around the circumference of the cylinder. Indeed, for a sufficiently small radius, a transition is observed, at which point the contact line is stable to transverse perturbations of all wavenumbers. In this regime, free surface instabilities lead to the development of wave patterns in the axial direction, and the flow features become perfectly analogous to the two-dimensional flow of a thin film down an inverted plane as studied by Lin & Kondic (Phys Fluids 22, 052105 (2010)). Finally, we simulate the flow of a single drop down the outside of the cylinder. Our results show that for drops with low volume, the cylinder curvature has the effect of increasing drop speed and hence promoting the phenomenon of pearling. On the other hand, drops with much larger volume evolve to form single long rivulets with a similar shape to a finger formed in the aforementioned simulations.

A reliable real-time transport protocol for networked control systems over wireless networks

Deploying wireless networks in networked control systems (NCSs) has become more and more popular during the last few years. As a typical type of real-time control systems, an NCS is sensitive to long and nondeterministic time delay and packet losses. However, the nature of the wireless channel has the potential to degrade the performance of NCS networks in many aspects, particularly in time delay and packet losses. Transport layer protocols could play an important role in providing both reliable and fast transmission service to fulfill NCS’s real-time transmission requirements. Unfortunately, none of the existing transport protocols, including the Transport Control Protocol (TCP) and the User Datagram Protocol (UDP), was designed for real-time control applications. Moreover, periodic data and sporadic data are two types of real-time data traffic with different priorities in an NCS. Due to the lack of support for prioritized transmission service, the real-time performance for periodic and sporadic data in an NCS network is often degraded significantly, particularly under congested network conditions. To address these problems, a new transport layer protocol called Reliable Real-Time Transport Protocol (RRTTP) is proposed in this thesis. As a UDP-based protocol, RRTTP inherits UDP’s simplicity and fast transmission features. To improve the reliability, a retransmission and an acknowledgement mechanism are designed in RRTTP to compensate for packet losses. They are able to avoid unnecessary retransmission of the out-of-date packets in NCSs, and collisions are unlikely to happen, and small transmission delay can be achieved. Moreover, a prioritized transmission mechanism is also designed in RRTTP to improve the real-time performance of NCS networks under congested traffic conditions. Furthermore, the proposed RRTTP is implemented in the Network Simulator 2 for comprehensive simulations. The simulation results demonstrate that RRTTP outperforms TCP and UDP in terms of real-time transmissions in an NCS over wireless networks.

Water Sensitive Urban Design (WSUD) application auditing

Background WSUD implementation in the Gold Coast City Council area commenced more than a decade ago. As a result, Council is expected to be in possession of WSUD assets valued at over tens of million dollars. The Gold Coast City Council is responsible for the maintenance and long-term management of these WSUD assets. Any shortcoming in implementation of best WSUD practices can potentially result in substantial liabilities and ineffective expenditure for the Council in addition to reduced efficiencies and outcomes. This highlights the importance of periodic auditing of WSUD implementation. Project scope The overall study entailed the following tasks: * A state-of-the-art literature review of the conceptual hydraulic and water quality treatment principles, current state of knowledge in relation to industry standards, best practice and identification of knowledge gaps in relation to maintenance and management practices and potential barriers to the implementation of WSUD. * Council stakeholder interviews to understand current practical issues in relation to the implementation of WSUD and the process of WSUD application from development application approval to asset management. * Field auditing of selected WSUD systems for condition assessment and identification of possible strengths and weaknesses in implementation. * Review of the Land Development Guidelines in order to identify any gaps and to propose recommendations for improvement. Conclusions Given below is a consolidated summary of the findings of the study undertaken. State-of-the-art literature review Though the conceptual framework for WSUD implementation is well established, the underlying theoretical knowledge underpinning the treatment processes and maintenance regimes and life cycle costing are still not well understood. Essentially, these are the recurring themes in the literature, namely, the inadequate understanding of treatment processes and lack of guidance to ensure specificity of maintenance regimes and life cycle costing of WSUDs. The fundamental barriers to successful WSUD implementation are: * Lack of knowledge transfer – This essentially relates to the lack of appropriate dissemination of research outcomes and the common absence of protocols for knowledge transfer within the same organisation. * Cultural barriers – These relate to social and institutional factors, including institutional inertia and the lack of clear understanding of the benefits. * Fragmented responsibilities – This results from poor administrative integration within local councils in relation to WSUDs. * Technical barriers – These relate to lack of knowledge on operational and maintenance practices which is compounded by model limitations and the lack of long-term quantitative performance evaluation data. * Lack of engineering standards – Despite the availability of numerous guidelines which are non-enforceable and can sometimes be confusing, there is a need for stringent engineering standards. The knowledge gaps in relation to WSUDs are only closing very slowly. Some of the common knowledge gaps identified in recent publications have been recognised almost a decade ago. The key knowledge gaps identified in the published literature are: * lack of knowledge on operational and maintenance practices; * lack of reliable methodology for identifying life cycle issues including costs; * lack of technical knowledge on system performance; * lack of guidance on retrofitting in existing developments. Based on the review of barriers to WSUD implementation and current knowledge gaps, the following were identified as core areas for further investigation: * performance evaluation of WSUD devices to enhance model development and to assess their viability in the context of environmental, economic and social drivers; establishing realistic life cycle costs to strengthen maintenance and asset management practices; * development of guidelines specific to retrofitting in view of the unique challenges posed by existing urban precincts together with guidance to ensure site specificity; establishment of a process for knowledge translation for enhancing currently available best practice guidelines; * identification of drivers and overcoming of barriers in the areas of institutional fragmentation, knowledge gaps and awareness of WSUD practices. GCCC stakeholder interviews Fourteen staff members involved in WSUD systems management in the Gold Coast City Council, representing four Directorates were interviewed using a standard questionnaire. The primary issues identified by the stakeholders were: * standardisation of WSUD terminology; * clear protocols for safeguarding devices during the construction phase; * engagement of all council stakeholders in the WSUD process from the initial phase; * limitations in the Land Development Guidelines; * ensuring public safety through design; * system siting to avoid conflicts with environmental and public use of open space; * provision of adequate access for maintenance; * integration of social and ecosystem issues to ensure long-term viability of systems in relation to both, vandalism and visual recreation; * lack of performance monitoring and inadequacy of the maintenance budget; * lack of technical training for staff involved in WSUD design approvals and maintenance; incentives for developers for acting responsibly in stormwater management. Field auditing of WSUD systems A representative cross section of WSUD systems in the Gold Coast were audited in the field. The following strengths and weaknesses in WSUD implementation were noted: * The implementation of WSUD systems in the field is not consistent. * The concerns raised by the stakeholders during the interviews in relation to WSUD implementation was validated from the observations from the field auditing, particularly in relation to the following: * safeguarding of devices during the construction phase * public safety * accessibility for maintenance * lack of performance monitoring by Council to assess system performance * inadequate maintenance of existing systems to suit site specific requirements. * A treatment train approach is not being consistently adopted. * Most of the systems audited have satisfactorily catered for public safety. Accessibility for maintenance has been satisfactorily catered for in most of the systems that were audited. * Systems are being commissioned prior to construction activities being substantially completed. * The hydraulic design of most systems appears to be satisfactory. * The design intent of the systems is not always clear. Review of Land Development Guidelines The Land Development Guidelines (TDG) was extensively reviewed and the following primary issues were noted in relation to WSUD implementation: * the LDG appears to have been prepared primarily to provide guidance to developers. It is not clear to what extent the guidelines are applicable to Council staff involved in WSUD maintenance and management; * Section 13 is very voluminous and appears to be a compilation of a series of individual documents resulting in difficulties in locating specific information, a lack of integration and duplication of information; * the LDG has been developed with a primary focus on new urban precinct development and the retrofitting of systems in existing developments has not been specifically discussed; * WSUDs are discussed in two different sections in the LDG and it is not clear which section takes precedence as there are inconsistencies between the two sections; there is inconsistent terminology being used; * there is a need for consolidation of information provided in different sections in the LDG; * there are inconsistencies in the design criteria provided; * there is a need for regular updating of the LDG to ensure that the information provided encompasses the state-of-the-art; * there is limited guidance provided for the preparation of maintenance plans and life cycle costing to assist developers in asset handover and to assist Council staff in assessment. * Based on these observations, eleven recommendations have been provided which are discussed below. Additionally, the stakeholder provided the following specific comments during the interviews in relation to the LDG: * lack of flexibility to cover the different stages of the life cycle of the systems; * no differentiation in projects undertaken by developers and Council; * inadequate information with regards to safety issues such as maximum standing water depth, fencing and safety barriers and public access; * lack of detailed design criteria in relation to Crime Prevention through Environmental Design, safety, amenity, environment, surrounding uses and impacts on surroundings; * inadequate information regarding maintenance requirements specific to the assessment and compliance phases; * recommendations for plantings are based primarily on landscape requirements rather than pollutant uptake capability. Recommendations With regards to the Land Development Guidelines, the following specific recommendations are provided: 1. the relevant sections and their extent of applicability to Council should be clearly identified; 2. integration of the different subsections within Section 13 and re-formatting the document for easy reference; 3. the maintenance guidelines provided in Section 13 should be translated to a maintenance manual for guidance of Council staff; 4. should consider extending the Guidelines to specifically encompass retrofitting of WSUD systems to existing urban precincts; 5. Section 3 needs to be revised to be made consistent with Section 13, to ensure priority for WSUD practices in urban precincts and to move away from conventional stormwater drainage design such as kerb and channelling; 6. it would also be good to specify as to which Section takes predominance in relation to stormwater drainage. It is expected that Section 13 would take predominance over the other sections in the LDG; 7. terminology needs to be made consistent to avoid confusion among developers and Council staff. Water Sensitive Urban Design is the term commonly used in Australia for stormwater quality treatment, rather than Stormwater Quality Improvement Devices. This once again underlines the need for ensuring consistency between Section 3 and Section 13; 8. it would also be good if there is a glossary of commonly used terms in relation to WSUD for use by all stakeholders and which should also be reflected in the LDG; 9. consolidation of all WSUD information into one section should be considered together with appropriate indicators in other LDG Sections regarding the availability of WSUD information. Ensuring consistency in the information provided is implied; 10. Section 13 should be updated at regular intervals to ensure the incorporation of the latest in research outcomes and incorporating criteria and guidance based on the state-of-the-art knowledge. The updating could be undertaken, say, in five year cycles. This would help to overcome the current lack of knowledge transfer; 11. the Council should consider commissioning specialised studies to extend the current knowledge base in relation to WSUD maintenance and life cycle costing. Additionally, Recommendation 10 is also applicable in this instance. The following additional recommendations are made based on the state-of-the-art literature review, stakeholder interviews and field auditing of WSUD systems: 1. Performance monitoring of existing systems to assess improvements to water quality, identify modifications and enhancements to improve performance; 2. Appropriate and monitored maintenance during different phases of development of built assets over time is needed to investigate the most appropriate time/phase of development to commission the final WSUD asset. 3. Undertake focussed investigations in the areas of WSUD maintenance and asset management in order to establish more realistic life cycle costs of systems and maintenance schedules; 4. the engagement of all relevant Council stakeholders from the initial stage of concept planning through to asset handover, and ongoing monitoring. This close engagement of internal stakeholders will assist in building a greater understanding of responsibilities and contribute to overcoming constraints imposed by fragmented responsibilities; 5. the undertaking of a public education program to inform the community of the benefits and ecosystem functions of WSUD systems; 6. technical training to impart state-of-the-art knowledge to staff involved in the approval of designs and maintenance and management of WSUD projects; 7. during the construction phase, it is important to ensure that appropriate measures to safeguard WSUD devices are implemented; 8. risks associated with potential public access to open water zones should be minimised with the application of appropriate safety measures; 9. system siting should ensure that potential conflicts are avoided with respect to public and ecosystem needs; 10. integration of social and ecosystem issues to ensure long-term viability of systems; provide incentives to developers who are proactive and responsible in the area of stormwater management.

An analysis of corporate related-party disclosure in the Asia-Pacific region

Related-party (RP) transactions are said to be commonly used opportunistically in business and contribute to corporate failures. While periodic disclosure is widely accepted as an effective means of monitoring such transactions, research is scant, particularly in countries where business dealings may be more susceptible to corruption. This study investigates the nature and extent of corporate RP disclosures across six countries in the Asia-Pacific region. The key finding indicates that companies in countries with stronger regulatory enforcement, shareholders’ protection, and control for corruption, have more transparent RP disclosures. This evidence potentially contributes to reforms aimed at strengthening RP disclosure and compliance.

Cross-layer design and optimization for wireless networked control systems

Wireless networked control systems (WNCSs) have been widely used in the areas of manufacturing and industrial processing over the last few years. They provide real-time control with a unique characteristic: periodic traffic. These systems have a time-critical requirement. Due to current wireless mechanisms, the WNCS performance suffers from long time-varying delays, packet dropout, and inefficient channel utilization. Current wirelessly networked applications like WNCSs are designed upon the layered architecture basis. The features of this layered architecture constrain the performance of these demanding applications. Numerous efforts have attempted to use cross-layer design (CLD) approaches to improve the performance of various networked applications. However, the existing research rarely considers large-scale networks and congestion network conditions in WNCSs. In addition, there is a lack of discussions on how to apply CLD approaches in WNCSs. This thesis proposes a cross-layer design methodology to address the issues of periodic traffic timeliness, as well as to promote the efficiency of channel utilization in WNCSs. The design of the proposed CLD is highlighted by the measurement of the underlying network condition, the classification of the network state, and the adjustment of sampling period between sensors and controllers. This period adjustment is able to maintain the minimally allowable sampling period, and also maximize the control performance. Extensive simulations are conducted using the network simulator NS-2 to evaluate the performance of the proposed CLD. The comparative studies involve two aspects of communications, with and without using the proposed CLD, respectively. The results show that the proposed CLD is capable of fulfilling the timeliness requirement under congested network conditions, and is also able to improve the channel utilization efficiency and the proportion of effective data in WNCSs.

Effects of air pollution exposure on adult bicycle commuters : an investigation of respiratory health, motorised traffic proximity and the utility of commute re-routing

Bicycle commuting has the potential to be an effective contributing solution to address some of modern society’s biggest issues, including cardiovascular disease, anthropogenic climate change and urban traffic congestion. However, individuals shifting from a passive to an active commute mode may be increasing their potential for air pollution exposure and the associated health risk. This project, consisting of three studies, was designed to investigate the health effects of bicycle commuters in relation to air pollution exposure, in a major city in Australia (Brisbane). The aims of the three studies were to: 1) examine the relationship of in-commute air pollution exposure perception, symptoms and risk management; 2) assess the efficacy of commute re-routing as a risk management strategy by determining the exposure potential profile of ultrafine particles along commute route alternatives of low and high proximity to motorised traffic; and, 3) evaluate the feasibility of implementing commute re-routing as a risk management strategy by monitoring ultrafine particle exposure and consequential physiological response from using commute route alternatives based on real-world circumstances; 3) investigate the potential of reducing exposure to ultrafine particles (UFP; < 0.1 µm) during bicycle commuting by lowering proximity to motorised traffic with real-time air pollution and acute inflammatory measurements in healthy individuals using their typical, and an alternative to their typical, bicycle commute route. The methods of the three studies included: 1) a questionnaire-based investigation with regular bicycle commuters in Brisbane, Australia. Participants (n = 153; age = 41 ± 11 yr; 28% female) reported the characteristics of their typical bicycle commute, along with exposure perception and acute respiratory symptoms, and amenability for using a respirator or re-routing their commute as risk management strategies; 2) inhaled particle counts measured along popular pre-identified bicycle commute route alterations of low (LOW) and high (HIGH) motorised traffic to the same inner-city destination at peak commute traffic times. During commute, real-time particle number concentration (PNC; mostly in the UFP range) and particle diameter (PD), heart and respiratory rate, geographical location, and meteorological variables were measured. To determine inhaled particle counts, ventilation rate was calculated from heart-rate-ventilation associations, produced from periodic exercise testing; 3) thirty-five healthy adults (mean ± SD: age = 39 ± 11 yr; 29% female) completed two return trips of their typical route (HIGH) and a pre-determined altered route of lower proximity to motorised traffic (LOW; determined by the proportion of on-road cycle paths). Particle number concentration (PNC) and diameter (PD) were monitored in real-time in-commute. Acute inflammatory indices of respiratory symptom incidence, lung function and spontaneous sputum (for inflammatory cell analyses) were collected immediately pre-commute, and one and three hours post-commute. The main results of the three studies are that: 1) healthy individuals reported a higher incidence of specific acute respiratory symptoms in- and post- (compared to pre-) commute (p < 0.05). The incidence of specific acute respiratory symptoms was significantly higher for participants with respiratory disorder history compared to healthy participants (p < 0.05). The incidence of in-commute offensive odour detection, and the perception of in-commute air pollution exposure, was significantly lower for participants with smoking history compared to healthy participants (p < 0.05). Females reported significantly higher incidence of in-commute air pollution exposure perception and other specific acute respiratory symptoms, and were more amenable to commute re-routing, compared to males (p < 0.05). Healthy individuals have indicated a higher incidence of acute respiratory symptoms in- and post- (compared to pre-) bicycle commuting, with female gender and respiratory disorder history indicating a comparably-higher susceptibility; 2) total mean PNC of LOW (compared to HIGH) was reduced (1.56 x e4 ± 0.38 x e4 versus 3.06 x e4 ± 0.53 x e4 ppcc; p = 0.012). Total estimated ventilation rate did not vary significantly between LOW and HIGH (43 ± 5 versus 46 ± 9 L•min; p = 0.136); however, due to total mean PNC, accumulated inhaled particle counts were 48% lower in LOW, compared to HIGH (7.6 x e8 ± 1.5 x e8 versus 14.6 x e8 ± 1.8 x e8; p = 0.003); 3) LOW resulted in a significant reduction in mean PNC (1.91 x e4 ± 0.93 x e4 ppcc vs. 2.95 x e4 ± 1.50 x e4 ppcc; p ≤ 0.001). Commute distance and duration were not significantly different between LOW and HIGH (12.8 ± 7.1 vs. 12.0 ± 6.9 km and 44 ± 17 vs. 42 ± 17 mins, respectively). Besides incidence of in-commute offensive odour detection (42 vs. 56 %; p = 0.019), incidence of dust and soot observation (33 vs. 47 %; p = 0.038) and nasopharyngeal irritation (31 vs. 41 %; p = 0.007), acute inflammatory indices were not significantly associated to in-commute PNC, nor were these indices reduced with LOW compared to HIGH. The main conclusions of the three studies are that: 1) the perception of air pollution exposure levels and the amenability to adopt exposure risk management strategies where applicable will aid the general population in shifting from passive, motorised transport modes to bicycle commuting; 2) for bicycle commuting at peak morning commute times, inhaled particle counts and therefore cardiopulmonary health risk may be substantially reduced by decreasing exposure to motorised traffic, which should be considered by both bicycle commuters and urban planners; 3) exposure to PNC, and the incidence of offensive odour and nasopharyngeal irritation, can be significantly reduced when utilising a strategy of lowering proximity to motorised traffic whilst bicycle commuting, without significantly increasing commute distance or duration, which may bring important benefits for both healthy and susceptible individuals. In summary, the findings from this project suggests that bicycle commuters can significantly lower their exposure to ultrafine particle emissions by varying their commute route to reduce proximity to motorised traffic and associated combustion emissions without necessarily affecting their time of commute. While the health endpoints assessed with healthy individuals were not indicative of acute health detriment, individuals with pre-disposing physiological-susceptibility may benefit considerably from this risk management strategy – a necessary research focus with the contemporary increased popularity of both promotion and participation in bicycle commuting.

Analysis of the design-construction supply chain in the thermal performance of sub-tropical and tropical housing

Background: In sub-tropical and tropical Queensland, a legacy of poor housing design,minimal building regulations with few compliance measures, an absence of post-construction performance evaluation and various social and market factors has led to a high and growing penetration of, and reliance on, air conditioners to provide thermal comfort for occupants. The pervasive reliance on air conditioners has arguably impacted on building forms, changed cultural expectations of comfort and social practices for achieving comfort, and may have resulted in a loss of skills in designing and constructing high performance building envelopes. Aim: The aim of this paper is to report on initial outcomes of a project that sought to determine how the predicted building thermal performance of twenty-five houses in subtropical and tropical Queensland compared with objective performance measures and comfort performance as perceived by occupants. The purpose of the project was to shed light on the role of various supply chain agents in the realisation of thermal performance outcomes. Methodology: The case study methodology embraced a socio-technical approach incorporating building science and sociology. Building simulation was used to model thermal performance under controlled comfort assumptions and adaptive comfort conditions. Actual indoor climate conditions were measured by temperature and relative humidity sensors placed throughout each house, whilst occupants’ expectations of thermal comfort and their self-reported behaviours were gathered through semi-structured interviews and periodic comfort surveys. Thermal imaging and air infiltration tests, along with building design documents, were analysed to evaluate the influence of various supply chain agents on the actual performance outcomes. Results: The results clearly show that in the housing supply chain – from designer to constructor to occupant – there is limited understanding from each agent of their role in contributing to, or inhibiting, occupants’ comfort.

Ingenuity pathways analysis of urine metabonomics phenotypes toxicity of gentamicin in multiple organs

We introduce the use of Ingenuity Pathway Analysis to analyzing global metabonomics in order to characterize phenotypically biochemical perturbations and the potential mechanisms of the gentamicin-induced toxicity in multiple organs. A single dose of gentamicin was administered to Sprague Dawley rats (200 mg/kg, n = 6) and urine samples were collected at -24-0 h pre-dosage, 0-24, 24-48, 48-72 and 72-96 h post-dosage of gentamicin. The urine metabonomics analysis was performed by UPLC/MS, and the mass spectra signals of the detected metabolites were systematically deconvoluted and analyzed by pattern recognition analyses (Heatmap, PCA and PLS-DA), revealing a time-dependency of the biochemical perturbations induced by gentamicin toxicity. As result, the holistic metabolome change induced by gentamicin toxicity in the animal's organisms was characterized. Several metabolites involved in amino acid metabolism were identified in urine, and it was confirmed that gentamicin biochemical perturbations can be foreseen from these biomarkers. Notoriously, it was found that gentamicin induced toxicity in multiple organs system in the laboratory rats. The proof-of-knowledge based Ingenuity Pathway Analysis revealed gentamicin induced liver and heart toxicity, along with the previously known toxicity in kidney. The metabolites creatine, nicotinic acid, prostaglandin E2, and cholic acid were identified and validated as phenotypic biomarkers of gentamicin induced toxicity. Altogether, the significance of the use of metabonomics analyses in the assessment of drug toxicity is highlighted once more; furthermore, this work demonstrated the powerful predictive potential of the Ingenuity Pathway Analysis to study of drug toxicity and its valuable complementation for metabonomics based assessment of the drug toxicity.

Plasma metabolomics reveals biomarkers of the atherosclerosis

Atherosclerotic cardiovascular disease remains the leading cause of morbidity and mortality in industrialized societies. The lack of metabolite biomarkers has impeded the clinical diagnosis of atherosclerosis so far. In this study, stable atherosclerosis patients (n=16) and age- and sex-matched non-atherosclerosis healthy subjects (n=28) were recruited from the local community (Harbin, P. R. China). The plasma was collected from each study subject and was subjected to metabolomics analysis by GC/MS. Pattern recognition analyses (principal components analysis, orthogonal partial least-squares discriminate analysis, and hierarchical clustering analysis) commonly demonstrated plasma metabolome, which was significantly different from atherosclerotic and non-atherosclerotic subjects. The development of atherosclerosis-induced metabolic perturbations of fatty acids, such as palmitate, stearate, and 1-monolinoleoylglycerol, was confirmed consistent with previous publication, showing that palmitate significantly contributes to atherosclerosis development via targeting apoptosis and inflammation pathways. Altogether, this study demonstrated that the development of atherosclerosis directly perturbed fatty acid metabolism, especially that of palmitate, which was confirmed as a phenotypic biomarker for clinical diagnosis of atherosclerosis.

Metabolite profiling and pathway analysis of acute hepatitis rats by UPLC-ESI MS combined with pattern recognition methods

BACKGROUND & AIMS Metabolomics is comprehensive analysis of low-molecular-weight endogenous metabolites in a biological sample. It could enable mapping of perturbations of early biochemical changes in diseases and hence provide an opportunity to develop predictive biomarkers that could provide valuable insights into the mechanisms of diseases. The aim of this study was to elucidate the changes in endogenous metabolites and to phenotype the metabolic profiling of d-galactosamine (GalN)-inducing acute hepatitis in rats by UPLC-ESI MS. METHODS The systemic biochemical actions of GalN administration (ip, 400 mg/kg) have been investigated in male wistar rats using conventional clinical chemistry, liver histopathology and metabolomic analysis of UPLC- ESI MS of urine. The urine was collected predose (-24 to 0 h) and 0-24, 24-48, 48-72, 72-96 h post-dose. Mass spectrometry of the urine was analysed visually and via conjunction with multivariate data analysis. RESULTS Results demonstrated that there was a time-dependent biochemical effect of GalN dosed on the levels of a range of low-molecular-weight metabolites in urine, which was correlated with developing phase of the GalN-inducing acute hepatitis. Urinary excretion of beta-hydroxybutanoic acid and citric acid was decreased following GalN dosing, whereas that of glycocholic acid, indole-3-acetic acid, sphinganine, n-acetyl-l-phenylalanine, cholic acid and creatinine excretion was increased, which suggests that several key metabolic pathways such as energy metabolism, lipid metabolism and amino acid metabolism were perturbed by GalN. CONCLUSION This metabolomic investigation demonstrates that this robust non-invasive tool offers insight into the metabolic states of diseases.

Estimating the robustness of long-haul train plans

In Australia, and elsewhere, the movement of trains on long-haul rail networks is usually planned in advance. Typically, a train plan is developed to confirm that the required train movements and track maintenance activities can occur. The plan specifies when track segments will be occupied by particular trains and maintenance activities. On the day of operation, a train controller monitors and controls the movement of trains and maintenance crews, and updates the train plan in response to unplanned disruptions. It can be difficult to predict how good a plan will be in practice. The main performance indicator for a train service should be reliability - the proportion of trains running the service that complete at or before the scheduled time. We define the robustness of a planned train service to be the expected reliability. The robustness of individual train services and for a train plan as a whole can be estimated by simulating the train plan many times with random, but realistic, perturbations to train departure times and segment durations, and then analysing the distributions of arrival times. This process can also be used to set arrival times that will achieve a desired level of robustness for each train service.

Epistatic effects of potassium channel variation on cardiac repolarization and atrial fibrillation risk

Objectives The aim of this study was to evaluate the role of cardiac K+ channel gene variants in families with atrial fibrillation (AF). Background The K+ channels play a major role in atrial repolarization but single mutations in cardiac K+ channel genes are infrequently present in AF families. The collective effect of background K+ channel variants of varying prevalence and effect size on the atrial substrate for AF is largely unexplored. Methods Genes encoding the major cardiac K+ channels were resequenced in 80 AF probands. Nonsynonymous coding sequence variants identified in AF probands were evaluated in 240 control subjects. Novel variants were characterized using patch-clamp techniques and in silico modeling was performed using the Courtemanche atrial cell model. Results Nineteen nonsynonymous variants in 9 genes were found, including 11 rare variants. Rare variants were more frequent in AF probands (18.8% vs. 4.2%, p < 0.001), and the mean number of variants was greater (0.21 vs. 0.04, p < 0.001). The majority of K+ channel variants individually had modest functional effects. Modeling simulations to evaluate combinations of K+ channel variants of varying population frequency indicated that simultaneous small perturbations of multiple current densities had nonlinear interactions and could result in substantial (>30 ms) shortening or lengthening of action potential duration as well as increased dispersion of repolarization. Conclusions Families with AF show an excess of rare functional K+ channel gene variants of varying phenotypic effect size that may contribute to an atrial arrhythmogenic substrate. Atrial cell modeling is a useful tool to assess epistatic interactions between multiple variants.

Synthesis and evaluation of resveratrol-based nitroxides as potential treatments for hypertension

The synthesis and evaluation of novel resveratrol-based nitroxides have been explored for the potential treatment of hypertension. New methodology for the direct aryl iodination of isoindoline and isoindoline nitroxide using periodic acid and potassium iodide in concentrated sulphuric acid was developed. Diiodinated tetramethyl and tetraethyl isoindolines and a tetramethyl isoindoline nitroxide were prepared in excellent yields (70 – 82%). A diiodinated tetraethyl isoindoline nitroxide was generated from the corresponding nitroxide in modest yield (37%) alongside iodinated nitrones. The mono-iodinated species were also generated in modest yields (34 – 48%). Incorporation of the nitroxide unit into the structure of resveratrol was achieved using palladium-catalysed Heck coupling. Use of the previously prepared iodo products 5-iodo-1,1,3,3-tetramethylisoindolin-2-yloyl 18 and 5,6-diiodo-1,1,3,3-tetramethylisoindolin-2-yloyl 22 gave resveratrol nitroxides 12 and 13 in yields of 50% (optimized) and 1.6% respectively. Preliminary evaluation of the resveratrol analogue 12 as a treatment for hypertension was undertaken in the DOCA-salt rat model. A reduction in systolic blood pressure as well as alleviation of ventricular hypertrophy was observed. A larger study involving the DOCA salt rats is currently in progress.

Weak links and dc SQUIDS on artificial nonsymmetric grain boundaries in YBa2Cu3O7-δ

We have studied weak links and dc-SQUIDs made from pulsed laser deposited YBa2Cu3O7-δ thin films on Y-ZrO 2 bicrystal substrates. The transport properties of the weak links were studied as a function of the misorientation angle (θ) between the two halves of the bicrystal and an exponential dependence of the weak link critical current density was observed for angles up to 40°at 77 K. Josephson effects with clear microwave and magnetic field responses were observed. An optimum dc-SQUID performance at 77 K was obtained for θ=32°. At this temperature, we achieved a periodic magnetic field response with a modulation depth of 12 μV.

Graphene ripples generated by grain boundaries in highly ordered pyrolytic graphite

Atomic scale periodic ripples that extend for several nanometers on the surface of adjacent graphitic grains have been observed for the first time on highly ordered pyrolitic graphite by UHV-STM. The ripples emanate from a grain boundary, and are explained in terms of a mechanical deformation due to the elastic strain accumulated along the GB, which is relieved out-of-plane in the topmost graphene layer. We present a molecular dynamics model that accounts for the formation of similar ripples as result of the lattice mismatch induced by two different grain orientations.