Binding and degradation of hyaluronan by human breast cancer cell lines expressing different forms of CD44 : correlation with invasive potential

In the present study, we examined a panel of human breast cancer cell lines with regard to their expression of CD44 and ability to bind and degrade hyaluronan. The cell lines expressed varying amounts of different molecular weight forms of CD44 (85-200 kDa) and, in general, those that expressed the greatest amounts of CD44 were the most invasive as judged by in vitro assays. In addition, the ability to bind and degrade hyaluronan was restricted to the cell lines expressing high levels of CD44, and both these functions were blocked by an antibody to CD44 (Hermes-1). Moreover, the rate of [3H]hyaluronan degradation was highly correlated with the amount of CD44 (r = 0.951, P < 0.0001), as well as with the invasive potential of the cells. Scatchard analysis of the [3H]hyaluronan binding of these cells revealed the existence of significant differences in both their binding capacity and their dissociation constant. To determine the source of this deviation, the different molecular weight forms of CD44 were partially separated by gel filtration chromatography. In all cell lines, the 85 kDa form was able to bind hyaluronan, although with different affinities. In contrast, not all of the high molecular weight forms of CD44 had this ability. These results illustrate the diversity of CD44 molecules in invasive tumor cells, and suggest that one of their major functions is to degrade hyaluronan.

Invasive and metastatic properties of MCF-7 cells and ras(H)-transfected MCF-7 cell lines

In vitro invasion and in vivo metastasis assays were performed with a panel of MCF-7 cells transfected with isogenic constructs of mutated ras(H) genes. Both increased levels of ras(H) expression and ras(H) oncogene activation increased activity of derivative cell lines in in vitro invasion assays. In vivo formation of spontaneous metastases was assessed after intradermal inoculation of MCF-7 cells in the vicinity of the mammary fat pads of ovariectomized nude mice. No metastases were seen in the absence of estradiol treatment of the mice. With estradiol supplementation of the mice both the ras(H)-transfected and control transfected cell lines gave a higher incidence of metastases than parental MCF-7 cells. Prolonged treatment of mice with exogenous estradiol (60 days vs. 21 days) resulted in more frequent metastases to liver and lung at the end of the 90-day observation period. In contrast to activated ras(H)-gene enhancement of metastatic capacity of rodent fibroblast and epithelial cell lines, there was no correlation of ras(H) expression with in vivo metastatic capacity of a human mammary carcinoma cell line.

A loop cancellation based active damping solution for constant power instability in vehicular power systems

In recent years, electric propulsion systems have increasingly been used in land, sea and air vehicles. The vehicular power systems are usually loaded with tightly regulated power electronic converters which tend to draw constant power. Since the constant power loads (CPLs) impose negative incremental resistance characteristics on the feeder system, they pose a potential threat to the stability of vehicular power systems. This effect becomes more significant in the presence of distribution lines between source and load in large vehicular power systems such as electric ships and more electric aircrafts. System transients such as sudden drop of converter side loads or increase of constant power requirement can cause complete system instability. Most of the existing research work focuses on the modeling and stabilization of DC vehicular power systems with CPLs. Only a few solutions are proposed to stabilize AC vehicular power systems with non-negligible distribution lines and CPLs. Therefore, this paper proposes a novel loop cancellation technique to eliminate constant power instability in AC vehicular power systems with a theoretically unbounded system stability region. Analysis is carried out on system stability with the proposed method and simulation results are presented to validate its effectiveness.

A national satellite-based land-use regression model for air pollution exposure assessment in Australia

Land-use regression (LUR) is a technique that can improve the accuracy of air pollution exposure assessment in epidemiological studies. Most LUR models are developed for single cities, which places limitations on their applicability to other locations. We sought to develop a model to predict nitrogen dioxide (NO2) concentrations with national coverage of Australia by using satellite observations of tropospheric NO2 columns combined with other predictor variables. We used a generalised estimating equation (GEE) model to predict annual and monthly average ambient NO2 concentrations measured by a national monitoring network from 2006 through 2011. The best annual model explained 81% of spatial variation in NO2 (absolute RMS error=1.4 ppb), while the best monthly model explained 76% (absolute RMS error=1.9 ppb). We applied our models to predict NO2 concentrations at the ~350,000 census mesh blocks across the country (a mesh block is the smallest spatial unit in the Australian census). National population-weighted average concentrations ranged from 7.3 ppb (2006) to 6.3 ppb (2011). We found that a simple approach using tropospheric NO2 column data yielded models with slightly better predictive ability than those produced using a more involved approach that required simulation of surface-to-column ratios. The models were capable of capturing within-urban variability in NO2, and offer the ability to estimate ambient NO2 concentrations at monthly and annual time scales across Australia from 2006–2011. We are making our model predictions freely available for research.

Building the safety case for UAS operations in support of natural disaster response

A framework supporting the systematic development of safety cases for Unmanned Aircraft System (UAS) operations in a broad range of civil and commercial applications is presented. The case study application is the use of UAS for disaster response. In those States where regulations do not preclude UAS operations altogether, approvals for UAS operations can be granted on a case-by-case basis contingent on the provision of a safety case acceptable to the relevant National Airworthiness Authority (NAA). A safety case for UAS operations must show how the risks associated with the hazards have been managed to an acceptable level. The foundational components necessary for structuring and assessing these safety cases have not yet been proposed. Barrier-bow-tie models are used in this paper to structure the safety case for the two primary hazards of 1) a ground impact, and 2) a Mid-Air Collision (MAC). The models establish the set of Risk Control Variables (RCVs) available to reduce the risk. For the ground-impact risk model, seven RCVs are identified which in combination govern the probability of an accident. Similarly, ten RCVs are identified within the MAC model. The effectiveness of the RCVs and how they can implemented in terms of processes, policies, devices, practices, or other actions for each of the case-study applications are discussed. The framework presented can provide for the more systematic and consistent regulation of UAS through a "safety target" approach.

Bicycle commuting and exposure to air pollution: A questionnaire-based investigation of perceptions, symptoms and risk management strategies

Background An increase in bicycle commuting participation may improve public health and traffic congestion in cities. Information on air pollution exposure (such as perception, symptoms and risk management) contributes to the responsible promotion of bicycle commuting participation. Methods To determine perceptions, symptoms and willingness for specific exposure risk management strategies of exposure to air pollution, a questionnaire-based cross-sectional investigation was conducted with adult bicycle commuters (n = 153; age = 41 ± 11 yr; 28% female). Results Frequency of acute respiratory signs and symptoms are positively-associated with in- and post-commute compared to pre-commute time periods (p < 0.05); greater positive-association is with respiratory disorder compared to healthy, and female compared to male, participants. The perception (although not signs or symptoms) of in-commute exposure to air pollution is positive-associated with the estimated level of in-commute proximity to motorised traffic. The majority of participants indicated a willingness (which varied with health status and gender) to adopt risk management strategies (with certain practical features) if shown to be appropriate and effective. Conclusions While acute signs and symptoms of air pollution exposure are indicated with bicycle commuting, and more so in susceptible individuals, there is willingness to manage exposure risk by adopting effective strategies with desirable features.

The influence of abrasive pretreatment on hot air drying of grape

The drying of grapes is a more complex process compared to the dehydration of other agricultural materials due to the necessity of a pretreatment operation prior to drying. Grape drying to produce raisins is a very slow process, due to the peculiar structure of grape peel, that is covered by a waxy layer.Its removal has benn so far carried out by using several chemical pre-treatments. However, they cause heterogeneity in the waxes removal and create microscopic cracks. In this paper an abrasive pretreatment for enhancing the drying rate and preserving the grape samples is proposed. Two cultivars of grape were investigated: Regina white grape and Red Globe red grape. The drying kinetics of untreated and treated samples were studied using a convective oven at 50 C. Fruit quality parameters such as sugar and organic acid contents, shrinkage, texture, peel damage (i.e. by SEM analysis) and rehydration capacity were studied to evaluate the effectiveness of abrasive pretreatment on raisins. Abrasive pretreatment contributed to reduce drying time and rehydration time. The treated and untreated dried grapes were significantly different (p<0.05) in sugar and in tartaric acid content. On the contrary, no significant differences (p<0.05) in malic and citric acids in texture peoperties between untreated and treated samples were observed.

23andMe Inc.: Patent law and lifestyle genetics

The venture, 23andMe Inc., raises a host of issues in respect of patent law, policy, and practice in respect of lifestyle genetics and personalised medicine. The company observes: ‘We recognize that the availability of personal genetic information raises important issues at the nexus of ethics, law, and public policy’. 23andMe Inc. has tested the boundaries of patent law, with its patent applications, which cut across information technology, medicine, and biotechnology. The company’s research raises fundamental issues about patentability, especially in light of the litigation in Bilski v. Kappos, Mayo Collaborative Services v. Prometheus Laboratories Inc. and Association for Molecular Pathology v. United States Patent and Trademark Office and Myriad Genetics Inc. There has been much debate and controversy over 23andMe Inc. filing patent applications – particularly in respect of its granted patent on ‘Polymorphisms associated with Parkinson’s Disease’. The direct-to-consumer marketing of genetic testing by 23andMe Inc. has also raised important questions of bioethics and human rights. It is queried whether the terms of service for 23andMe Inc. provide adequate recognition of the concepts of informed consent and benefit-sharing, especially in light of litigation in this area in the United States. Given the patent thickets surrounding genetic testing, the case study of 23andMe Inc. also highlights questions about patent infringement and patent exceptions. The future reform of patent law, policy, and practice needs to take into account new developments in lifestyle genetics and personalised medicine – as exemplified by 23andMe Inc.

Breakfast at Tiffany's': eBay Inc., trade mark law, and counterfeiting

In an exploration of intellectual property and fashion, this article examines the question of the intermediary liability of online auction-houses for counterfeiting. In the United States, the illustrious jewellery store, Tiffany & Co, brought a legal action against eBay Inc, alleging direct trademark infringement, contributory trademark infringement, false advertising, unfair competition and trademark dilution. The luxury store depicted the online auction-house as a pirate bazaar, a flea-market and a haven for counterfeiting. During epic litigation, eBay Inc successfully defended itself against these allegations in a United States District Court and the United States Court of Appeals for the Second Circuit. Tiffany & Co made a desperate, unsuccessful effort to appeal the matter to the Supreme Court of the United States. The matter featured a number of interventions from amicus curiae — Tiffany was supported by Coty, the Fashion Designer's Guild, and the International Anticounterfeiting Coalition, while eBay was defended by publicly-spirited civil society groups such as Electronic Frontier Foundation, Public Citizen, and Public Knowledge as well as Yahoo!, Google Inc, Amazon.com, and associations representing telecommunications carriers and internet service providers. The litigation in the United States can be counterpointed with the fusillade of legal action against eBay in the European Union. In contrast to Tiffany & Co, Louis Vuitton triumphed over eBay in the French courts — claiming its victory as vindication of the need to protect the commercial interests and cultural heritage of France. However, eBay has fared somewhat better in a dispute with L’Oréal in Great Britain and the European Court of Justice. It is argued that, in a time of flux and uncertainty, Australia should follow the position of the United States courts in Tiffany & Co v eBay Inc. The final part examines the ramifications of this litigation over online auction-houses for trade mark law reform and consumer rights; parallel disputes over intermediary liability and safe harbours in the field of copyright law and the Anti-Counterfeiting Trade Agreement 2010. The conclusion calls for a revision of trade mark law, animated by a respect for consumers’ rights and interests in the electronic marketplace.

Lock the gate: Fracking, investor-state dispute settlement, and the Trans-Pacific Partnership

There has been much debate about the relationship between international trade, the environment, biodiversity protection, and climate change.The Obama Administration has pushed such issues into sharp relief, with its advocacy for sweeping international trade agreements, such as the Trans-Pacific Partnership and the Trans-Atlantic Trade and Investment Partnership. There has been much public concern about the impact of the mega-trade deals upon the protection of the environment. In particular, there has been a debate about whether the Trans-Pacific Partnership will promote dirty fracking. Will the Trans-Pacific Partnership transform the Pacific Rim into a Gasland?There has been a particular focus upon investor-state dispute settlement being used by unconventional mining companies. Investor-state dispute settlement is a mechanism which enables foreign investors to seek compensation from national governments at international arbitration tribunals. In her prescient 2009 book, The Expropriation of Environmental Governance, Kyla Tienhaara foresaw the rise of investor-state dispute resolution of environmental matters. She observed:'Over the last decade there has been an explosive increase of cases investment arbitration. This is significant in terms of not only the number of disputes that have arisen and the number of states that have been involved, but also the novel types of dispute that have emerged. Rather than solely involving straightforward incidences of nationalization or breach of contract, modern disputes often revolve around public policy measures and implicate sensitive issues such as access to drinking water, development on sacred indigenous sites and the protection of biodiversity.'In her study, Kyla Tienhaara observed that investment agreements, foreign investment contracts and investment arbitration had significant implications for the protection for the protection of the environment. She concluded that arbitrators have made it clear that they can, and will, award compensation to investors that claim to have been harmed by environmental regulation. She also found that some of the cases suggest that the mere threat of arbitration is sufficient to chill environmental policy development. Tienhaara was equally concerned by the possibility that a government may use the threat of arbitration as an excuse or cover for its failure to improve environmental regulation. In her view, it is evident that arbitrators have expropriated certain fundamental aspects of environmental governance from states. Tienhaara held: As a result, environmental regulation has become riskier, more expensive, and less democratic, especially in developing countries. This article provides a comparative analysis of the battles over fracking, investment, trade, and the environment in a number of key jurisdictions including the United States, Canada, Australia, and New Zealand. Part 1 focuses upon the United States. Part 2 examines the dispute between the Lone Pine Resources Inc. and the Government of Canada over a fracking moratorium in Quebec. Part 3 charts the rise of the Lock the Gate Alliance in Australia, and its demands for a moratorium in respect of coal seam gas and unconventional mining. Part 4 focuses upon parallel developments in New Zealand. This article concludes that Pacific Rim countries should withdraw from investor-state dispute settlement procedures, because of the threat posed to environmental regulation in respect of air, land, and water.

Whole-genome linkage analysis of rheumatoid arthritis susceptibility loci in 252 affected sibling pairs in the United Kingdom

Objective. To undertake a systematic wholegenome screen to identify regions exhibiting genetic linkage to rheumatoid arthritis (RA). Methods. Two hundred fifty-two RA-affected sibling pairs from 182 UK families were genotyped using 365 highly informative microsatellite markers. Microsatellite genotyping was performed using fluorescent polymerase chain reaction primers and semiautomated DNA sequencing technology. Linkage analysis was undertaken using MAPMAKER/SIBS for single-point and multipoint analysis. Results. Significant linkage (maximum logarithm of odds score 4.7 [P = 0.000003] at marker D6S276, 1 cM from HLA-DRB1) was identified around the major histocompatibility complex (MHC) region on chromosome 6. Suggestive linkage (P < 7.4 × 10-4) was identified on chromosome 6q by single- and multipoint analysis. Ten other sites of nominal linkage (P < 0.05) were identified on chromosomes 3p, 4q, 7p, 2 regions of 10q, 2 regions of 14q, 16p, 21q, and Xq by single-point analysis and on 3 sites (1q, 14q, and 14q) by multipoint analysis. Conclusion. Linkage to the MHC region was confirmed. Eleven non-HLA regions demonstrated evidence of suggestive or nominal linkage, but none reached the genome-wide threshold for significant linkage (P = 2.2 × 10-5). Results of previous genome screens have suggested that 6 of these regions may be involved in RA susceptibility.

Development and validation of a multilevel model for predicting workload under routine and nonroutine conditions in an air traffic management center

Objective: The aim of this study was to develop a model capable of predicting variability in the mental workload experienced by frontline operators under routine and nonroutine conditions. Background: Excess workload is a risk that needs to be managed in safety-critical industries. Predictive models are needed to manage this risk effectively yet are difficult to develop. Much of the difficulty stems from the fact that workload prediction is a multilevel problem. Method: A multilevel workload model was developed in Study 1 with data collected from an en route air traffic management center. Dynamic density metrics were used to predict variability in workload within and between work units while controlling for variability among raters. The model was cross-validated in Studies 2 and 3 with the use of a high-fidelity simulator. Results: Reported workload generally remained within the bounds of the 90% prediction interval in Studies 2 and 3. Workload crossed the upper bound of the prediction interval only under nonroutine conditions. Qualitative analyses suggest that nonroutine events caused workload to cross the upper bound of the prediction interval because the controllers could not manage their workload strategically. Conclusion: The model performed well under both routine and nonroutine conditions and over different patterns of workload variation. Application: Workload prediction models can be used to support both strategic and tactical workload management. Strategic uses include the analysis of historical and projected workflows and the assessment of staffing needs. Tactical uses include the dynamic reallocation of resources to meet changes in demand.

Evaluating temperate species for the subtropics. 1. Annual ryegrasses

In the subtropics of Australia, irrigated temperate species are the key to reliable cool season feed on dairy farms. Persistence of perennial species is a major limitation to achieving reliable production from irrigated areas and yearly sowings of annual ryegrasses have replaced them as the most productive cool season forage production system in the subtropics. This series of experiments evaluated the yield, and resistance to rust damage, of commercially available cultivars and breeders' lines of annually sown ryegrasses (Lolium multiflorum, L. rigidum, L. x boucheanum and L perenne) in pure, nitrogen-fertilised swards under irrigation in the subtropics over a 22-year period. Barberia and Aristocrat 2 were the most adapted cultivars for subtropical conditions, producing high yields (119 and 114% of mean yield, respectively) and demonstrating the least rust damage. Newer selections from New Zealand, South African, United States of America and European breeding programs are performing better under subtropical conditions than older cultivars, particularly if a component of the selection process has been conducted in that environment. Cultivars such as Passerei Plus, Crusader, Hulk, Status and Warrior are examples of this process, producing between 105 and 115% of mean yield. Yields of annual ryegrass cultivars, which have been available or still are available for sale in Australia, ranged from 14-30 t/ha DM, depending on cultivar, site and seasonal conditions. Yields were lower at the site, which had inferior soil structure and drainage. Up to 50% of yield was produced in the 3 winter months. There was a trend towards improved yields and better tolerance of crown rust from experimental lines in the subtropics, as breeders strive for wider adaptation. Around 70% of the variation in total yield of annual ryegrass and 50 and 60% of the variation in winter and spring yield, respectively, were significantly explained by cultivar, site and climatic variables in autumn, winter and spring. While level of rust damage had no effect on total or seasonal yields, it affected the amount of green leaf available in spring. Under subtropical conditions, winter, spring and overall (autumn to mid-summer) temperatures influenced the- development of rust, which along with cultivar, accounted for 46% of the variation in rust damage. Cultivars showed a range of adaptation, with some performing well only under adverse conditions, some being well adapted to all conditions and some which performed well only under favoured conditions. Cultivars with high winter yields were most suited to subtropical conditions and included Aristocrat 2 (now released as CM 108), Barberia, Warrior, Crusader, Status, Passerei Plus and Hulk. Short growing season types such as Winter Star and T Rex performed well in winter but achieved lower total production, and long season cultivars such as Flanker rarely achieved their potential because of unfavourable conditions in late summer.