In silico biology : making the most of parallel computing

Biological systems are typically complex and adaptive, involving large numbers of entities, or organisms, and many-layered interactions between these. System behaviour evolves over time, and typically benefits from previous experience by retaining memory of previous events. Given the dynamic nature of these phenomena, it is non-trivial to provide a comprehensive description of complex adaptive systems and, in particular, to define the importance and contribution of low-level unsupervised interactions to the overall evolution process. In this chapter, the authors focus on the application of the agent-based paradigm in the context of the immune response to HIV. Explicit implementation of lymph nodes and the associated lymph network, including lymphatic chain structure, is a key objective, and requires parallelisation of the model. Steps taken towards an optimal communication strategy are detailed.

Multi-parametric hydrogels support 3D in vitro bioengineered microenvironment models of tumour angiogenesis

Tumour microenvironment greatly influences the development and metastasis of cancer progression. The development of three dimensional (3D) culture models which mimic that displayed in vivo can improve cancer biology studies and accelerate novel anticancer drug screening. Inspired by a systems biology approach, we have formed 3D in vitro bioengineered tumour angiogenesis microenvironments within a glycosaminoglycan-based hydrogel culture system. This microenvironment model can routinely recreate breast and prostate tumour vascularisation. The multiple cell types cultured within this model were less sensitive to chemotherapy when compared with two dimensional (2D) cultures, and displayed comparative tumour regression to that displayed in vivo. These features highlight the use of our in vitro culture model as a complementary testing platform in conjunction with animal models, addressing key reduction and replacement goals of the future. We anticipate that this biomimetic model will provide a platform for the in-depth analysis of cancer development and the discovery of novel therapeutic targets.

The use of ecosystem services valuation in Australian coastal zone management

The use and influence of ecosystem services valuation in management decision-making, particularly as it relates to coastal zone management, remains largely unexplored in the academic literature. A recent Australia-wide survey of decision-makers involved in coastal zone management examined if, how and to what extent economic valuation of coastal and marine ecosystem services is used in, and influences, decision-making in Australia. The survey also identified a set of cases where economic valuation of ecosystem services was used for decision-making, and reasons why economic values may or may not be considered in the decision-making process. This paper details the method and results from this survey. Overall, there is strong empirical evidence that economic valuation of ecosystem services is used, but with important variation across coastal and marine management contexts. However, the impact of ecosystem services valuation on policy appears to be globally weak.

Effect of ocular hypotony secondary to cyclodialysis cleft on corneal topography

PURPOSE: To report the changes in corneal topography in 2 cases of ocular hypotony induced by cyclodialysis cleft after blunt trauma, which were successfully treated by argon laser photocoagulation. METHODS: For both patients, a full ophthalmic clinical examination and corneal topography were performed before and after argon laser cleft closure. RESULTS: In the first case, the corneal topography showed 3.81-D astigmatism at 96 degrees, which was reduced to 1.1 D at 124 degrees 1 week after treatment and 0.66 D at 122 degrees at 3 weeks after treatment. In the second case, the corneal astigmatism was 3.91 D at 104 degrees, which decreased to 1.44 D at 104 degrees and 0.35 D at 118 degrees at 1 week and 4 months after treatment, respectively. CONCLUSIONS: In both cases, the with-the-rule astigmatism reduced significantly after successful closure of the cleft and an increase in intraocular pressure.

A Deweyan experience economy for higher education : The case of the Australian Indie 100 Music Event

In this essay we argue that a Deweyan experience economy will best support the higher education (HE) sector in the future, and we draw a contrast between that economy and the sector’s current focus on informational concerns, as expressed by the recent rush to Massive Open Online Courses (MOOCs) and other mass online informational offerings. We base our argument on current developments in music education and music technology that we see as being preemptive of wider trends. We use examples from a three-year study of online and offline music pedagogies and outline a four-year experiment in developing a pedagogical experience economy to illustrate a theoretical position informed by John Dewey’s theory of experience,Pierre Bourdieu’s theory of habitus and capital, and recent work in economic geography on epistemic communities. We argue further that the future of the HE sector is local rather than global, experiential rather than informational, and that therefore a continued informational approach to the future of HE risks undermining the sector.

Corresponding geographies: Remapping work and workplace in the age of digital media

This essay makes three related claims about digital media creative clusters through a case study of the Hub in Glasgow, Scotland. First, online social networking platforms are an increasingly “common sense” feature that property developers include to attract media workers to purpose-built properties. Second, integrating and managing professional identities through the construction of place are considered necessary to promote that place to a larger audience. Finally, reorganizing place in this way refashions creative work as a more nebulous concept, a process that integrates formerly distinct aspects of our work and nonwork lives into the common pursuit of innovation for economic gain.

Strain- and host species-specific inflammasome activation, IL-1β release, and cell death in macrophages infected with uropathogenic Escherichia coli

Uropathogenic Escherichia coli (UPEC) is the main etiological agent of urinary tract infections (UTIs). Little is known about interactions between UPEC and the inflammasome, a key innate immune pathway. Here we show that UPEC strains CFT073 and UTI89 trigger inflammasome activation and lytic cell death in human macrophages. Several other UPEC strains, including two multidrug-resistant ST131 isolates, did not kill macrophages. In mouse macrophages, UTI89 triggered cell death only at a high multiplicity of infection, and CFT073-mediated inflammasome responses were completely NLRP3-dependent. Surprisingly, CFT073- and UTI89-mediated responses only partially depended on NLRP3 in human macrophages. In these cells, NLRP3 was required for interleukin-1β (IL-1β) maturation, but contributed only marginally to cell death. Similarly, caspase-1 inhibition did not block cell death in human macrophages. In keeping with such differences, the pore-forming toxin α-hemolysin mediated a substantial proportion of CFT073-triggered IL-1β secretion in mouse but not human macrophages. There was also a more substantial α-hemolysin-independent cell death response in human vs. mouse macrophages. Thus, in mouse macrophages, CFT073-triggered inflammasome responses are completely NLRP3-dependent, and largely α-hemolysin-dependent. In contrast, UPEC activates an NLRP3-independent cell death pathway and an α-hemolysin-independent IL-1β secretion pathway in human macrophages. This has important implications for understanding UTI in humans.

Assessment of antenna characteristic effects on pedestrian and cyclists travel-time estimation based on Bluetooth and WiFi MAC addresses

Monitoring pedestrian and cyclists movement is an important area of research in transport, crowd safety, urban design and human behaviour assessment areas. Media Access Control (MAC) address data has been recently used as potential information for extracting features from people’s movement. MAC addresses are unique identifiers of WiFi and Bluetooth wireless technologies in smart electronics devices such as mobile phones, laptops and tablets. The unique number of each WiFi and Bluetooth MAC address can be captured and stored by MAC address scanners. MAC addresses data in fact allows for unannounced, non-participatory, and tracking of people. The use of MAC data for tracking people has been focused recently for applying in mass events, shopping centres, airports, train stations etc. In terms of travel time estimation, setting up a scanner with a big value of antenna’s gain is usually recommended for highways and main roads to track vehicle’s movements, whereas big gains can have some drawbacks in case of pedestrian and cyclists. Pedestrian and cyclists mainly move in built distinctions and city pathways where there is significant noises from other fixed WiFi and Bluetooth. Big antenna’s gains will cover wide areas that results in scanning more samples from pedestrians and cyclists’ MAC device. However, anomalies (such fixed devices) may be captured that increase the complexity and processing time of data analysis. On the other hand, small gain antennas will have lesser anomalies in the data but at the cost of lower overall sample size of pedestrian and cyclist’s data. This paper studies the effect of antenna characteristics on MAC address data in terms of travel-time estimation for pedestrians and cyclists. The results of the empirical case study compare the effects of small and big antenna gains in order to suggest optimal set up for increasing the accuracy of pedestrians and cyclists’ travel-time estimation.

Virtual countries: Internet domain names and geographical terms

This paper examines the dispute between the Seattle company Virtual Countries Inc. and the Republic of South Africa over the ownership of the domain name address southafrica.com. The first part of the paper deals with the pre-emptive litigation taken by Virtual Countries Inc. in a District Court of the United States. The second part considers the possible arbitration of the dispute under the Uniform Domain Name Dispute Resolution Process of the Internet Corporation for Assigned Names and Numbers (ICANN) and examines the wider implications of this dispute for the jurisdiction and the governance of ICANN. The final section of the paper evaluates the Final Report of the Second WIPO Internet Domain Name Process.

Breaches of lease between exercise of option to renew and expiry of lease in Queensland

The decision of Greppo v Jam-Cal Bundaberg Pty Ltd [2015] QCA 131 illustrates a defect in s 128 of the Property Law Act 1974(Qld) which gives a right to a lessee to apply for relief against forfeiture against loss of a right to exercise an option to renew. The defect arises because the legislation does not adequately deal with breaches that occur after the exercise of the option but before the expiry of the lease. Most commercial leases of all kinds have a standard provisions, as the lease in this case, as a conditions of the exercise of the option to renew that the lessee will have given notice of exercise within the time specified to the lessor and will have up to the date of expiry of the lease paid all rent and observed all lessee’s covenants. The difficulties occur because invariably an option must be exercised before the expiry of the lease when a lessee may not be in breach of the lease but may later prior to the expiry of the lease fall into breach. As this decision indicates,at least in Queensland, that the lessee who desires to challenge the lessor’s right to enforce those conditions can neither seek relief under s 128 against forfeiture of the right to exercise the option ,or indeed, under s 124 of the Property Law Act 1974 to preserve the agreement for lease brought about by the otherwise regular exercise of the option to renew. The decision cries out for legislative reform along the lines of s 133E of the Conveyancing Act 1919(NSW) which was amended in 2001 to meet this contingency.

Costing the Australian National Hand Hygiene Initiative

Background The Australian National Hand Hygiene Initiative (NHHI) is a major patient safety programme co-ordinated by Hand Hygiene Australia (HHA) and funded by the Australian Commission for Safety and Quality in Health Care. The annual costs of running this programme need to be understood to know the cost-effectiveness of a decision to sustain it as part of health services. Aim To estimate the annual health services cost of running the NHHI; the set-up costs are excluded. Methods A health services perspective was adopted for the costing and collected data from the 50 largest public hospitals in Australia that implemented the initiative, covering all states and territories. The costs of HHA, the costs to the state-level infection-prevention groups, the costs incurred by each acute hospital, and the costs for additional alcohol-based hand rub are all included. Findings The programme cost AU$5.56 million each year (US$5.76, £3.63 million). Most of the cost is incurred at the hospital level (65%) and arose from the extra time taken for auditing hand hygiene compliance and doing education and training. On average, each infection control practitioner spent 5 h per week on the NHHI, and the running cost per annum to their hospital was approximately AU$120,000 in 2012 (US$124,000, £78,000). Conclusion Good estimates of the total costs of this programme are fundamental to understanding the cost-effectiveness of implementing the NHHI. This paper reports transparent costing methods, and the results include their uncertainty.

Validity of currently used cutoff values of body mass index as a measure of obesity in Sri Lankan children

The aim of the study was to determine the reliability of body mass index based (BMI) cutoff values in diagnosing obesity among Sri Lankan children. Height, weight, waist circumference (WC) and hip circumference (HC) in 282 children were measured. Total body water was determined by deuterium dilution and fat mass (FM) derived using age and gender specific constants. A percentage FM of 30% for girls and 25% for boys were considered as cutoff levels for obesity. Two hundred and eighty two children (M/F: 158/124) were studied and 99 (80%) girls and 72 (45.5%) boys were obese based on % body fat. Eight (6.4%) girls and nine (5.7%) boys were obese based on International Obesity Task Force (IOTF) cutoff values. Percentage FM and WC centile charts were able to diagnose a significant proportion of children as true obese children. The FM and BMI were closely associated in both girls (r = 0.82, p < 0.001) and boys (r = 0.87, p < 0.001). Percentage FM and BMI had a very low but significant association; girls (r = 0.32, p < 0.001) and boys (r = 0.68, p < 0.001). FM had a significant association with WC and HC. BMI based cutoff values had a specificity of 100% but a very low sensitivity, varying between 8% and 23.6%. BMI is a poor indicator of the percentage fat and the commonly used cutoff values were not sensitive to detect cases of childhood obesity in Sri Lankan children.

Genome-wide association study to identify genetic determinants of severe asthma

Background: The genetic basis for developing asthma has been extensively studied. However, association studies to date have mostly focused on mild to moderate disease and genetic risk factors for severe asthma remain unclear. Objective: To identify common genetic variants affecting susceptibility to severe asthma. Methods: A genome-wide association study was undertaken in 933 European ancestry individuals with severe asthma based on Global Initiative for Asthma (GINA) criteria 3 or above and 3346 clean controls. After standard quality control measures, the association of 480 889 genotyped single nucleotide polymorphisms (SNPs) was tested. To improve the resolution of the association signals identified, non-genotyped SNPs were imputed in these regions using a dense reference panel of SNP genotypes from the 1000 Genomes Project. Then replication of SNPs of interest was undertaken in a further 231 cases and 1345 controls and a meta-analysis was performed to combine the results across studies. Results: An association was confirmed in subjects with severe asthma of loci previously identified for association with mild to moderate asthma. The strongest evidence was seen for the ORMDL3/GSDMB locus on chromosome 17q12-21 (rs4794820, p=1.03×10 (-8)following meta-analysis) meeting genome-wide significance. Strong evidence was also found for the IL1RL1/IL18R1 locus on 2q12 (rs9807989, p=5.59×10 (-8) following meta-analysis) just below this threshold. No novel loci for susceptibility to severe asthma met strict criteria for genome-wide significance. Conclusions: The largest genome-wide association study of severe asthma to date was carried out and strong evidence found for the association of two previously identified asthma susceptibility loci in patients with severe disease. A number of novel regions with suggestive evidence were also identified warranting further study.

Spatial B-jump at sudden channel enlargements with abrupt drop

An analytical and experimental study of the hydraulic jump in stilling basins with abrupt drop and sudden enlargement, called the spatial B-jump here, is carried out for finding the sequent depth ratio and resulting energy dissipation. The spatial B-jump studied has its toe downstream of the expansion section, and the stream lines at the toe are characterized by downward curvature. An expression is obtained for the sequent depth ratio based on the momentum equation with suitable assumptions for the extra pressure force term because of the abrupt drop in the bed and sudden enlargement in the basin width. Predictions compare favorably with experiments. It is shown that the spatial B-jump needs less tailwater depth, thereby enhancing the stability of the jump when compared either with spatial jump, which forms in sudden expanding channels, or with B-jump, which forms in a channel with an abrupt drop in bed. It is also shown that there is a significant increase in relative energy loss for the spatial B-jump compared to either the spatial jump or B-jump alone.

Dynamics of ribonuclease A and ribonuclease S: Computational and experimental studies

RNase S is a complex consisting of two proteolytic fragments of RNase A: the S peptide (residues 1-20) and S protein (residues 21-124). RNase S and RNase A have very similar X-ray structures and enzymatic activities. previous experiments have shown increased rates of hydrogen exchange and greater sensitivity to tryptic cleavage for RNase S relative to RNase A. It has therefore been asserted that the RNase S complex is considerably more dynamically flexible than RNase A. In the present study we examine the differences in the dynamics of RNaseS and RNase A computationally, by MD simulations, and experimentally, using trypsin cleavage as a probe of dynamics. The fluctuations around the average solution structure during the simulation were analyzed by measuring the RMS deviation in coordinates. No significant differences between RNase S and RNase A dynamics were observed in the simulations. We were able to account for the apparent discrepancy between simulation and experiment by a simple model, According to this model, the experimentally observed differences in dynamics can be quantitatively explained by the small amounts of free S peptide and S protein that are present in equilibrium with the RNase S complex. Thus, folded RNase A and the RNase S complex have identical dynamic behavior, despite the presence of a break in polypeptide chain between residues 20 and 21 in the latter molecule. This is in contrast to what has been widely believed for over 30 years about this important fragment complementation system.