A review of the profile of endothelin axis in cancer and its management

The endothelins and their associated receptors are important controllers of vascular growth, inflammation and vascular tone. In cancer, they have roles in the control of numerous factors in cancer development and progression, including angiogenesis, stromal reaction, epithelial mesenchymal transitions, apoptosis, invasion, metastases and drug resistance. Also, we consider current information on the role of this signalling system in cancer and examine the state of the current cell, animal and clinical trials utilizing endothelin targeted drugs for cancer management. Although targeting the endothelin axis in cell lines and xenografts show some promise in retarding cellular growth, results from limited clinical trials in prostatic cancer are less encouraging and did not offer significant survival benefit. The ability to target both cancer cells and vasculature via endothelin is an important consideration that necessitates the further refining of therapeutic strategies as we continue to explore the possibilities of the endothelin axis in cancer treatment.

Carcinoma ex pleomorphic adenoma : a comprehensive review of clinical, pathological and molecular data

Carcinoma ex pleomorphic adenoma (Ca ex PA) is a carcinoma arising from a primary or recurrent benign pleomorphic adenoma. It often poses a diagnostic challenge to clinicians and pathologists. This study intends to review the literature and highlight the current clinical and molecular perspectives about this entity. The most common clinical presentation of CA ex PA is of a firm mass in the parotid gland. The proportion of adenoma and carcinoma components determines the macroscopic features of this neoplasm. The entity is difficult to diagnose pre-operatively. Pathologic assessment is the gold standard for making the diagnosis. Treatment for Ca ex PA often involves an ablative surgical procedure which may be followed by radiotherapy. Overall, patients with Ca ex PA have a poor prognosis. Accurate diagnosis and aggressive surgical management of patients presenting with Ca ex PA can increase their survival rates. Molecular studies have revealed that the development of Ca ex PA follows a multi-step model of carcinogenesis, with the progressive loss of heterozygosity at chromosomal arms 8q, then 12q and finally 17p. There are specific candidate genes in these regions that are associated with particular stages in the progression of Ca ex PA. In addition, many genes which regulate tumour suppression, cell cycle control, growth factors and cell-cell adhesion play a role in the development and progression of Ca ex PA. It is hopeful that these molecular data can give clues for the diagnosis and management of the disease.

Suppression of mRNAs encoding tegument tetraspanins from schistosoma mansoni results in impaired tegument turnover

Schistosomes express a family of integral membrane proteins, called tetraspanins (TSPs), in the outer surface membranes of the tegument. Two of these tetraspanins, Sm-TSP-1 and Sm-TSP-2, confer protection as vaccines in mice, and individuals who are naturally resistant to S. mansoni infection mount a strong IgG response to Sm-TSP-2. To determine their functions in the tegument of S. mansoni we used RNA interference to silence expression of Sm-tsp-1 and Sm-tsp-2 mRNAs. Soaking of parasites in Sm-tsp dsRNAs resulted in 61% (p = 0.009) and 74% (p = 0.009) reductions in Sm-tsp-1 and Sm-tsp-2 transcription levels, respectively, in adult worms, and 67%–75% (p = 0.011) and 69%–89% (p = 0.004) reductions in Sm-tsp-1 and Sm-tsp-2 transcription levels, respectively, in schistosomula compared to worms treated with irrelevant control (luciferase) dsRNA. Ultrastructural morphology of adult worms treated in vitro with Sm-tsp-2 dsRNA displayed a distinctly vacuolated and thinner tegument compared with controls. Schistosomula exposed in vitro to Sm-tsp-2 dsRNA had a significantly thinner and more vacuolated tegument, and morphology consistent with a failure of tegumentary invaginations to close. Injection of mice with schistosomula that had been electroporated with Sm-tsp-1 and Sm-tsp-2 dsRNAs resulted in 61% (p = 0.005) and 83% (p = 0.002) reductions in the numbers of parasites recovered from the mesenteries four weeks later when compared to dsRNA-treated controls. These results imply that tetraspanins play important structural roles impacting tegument development, maturation or stability.

Which industry is greener? An empirical study of nine industries in OECD countries

This study analyzed the relationship between the CO2 emissions of different industries and economic growth in OECD countries from 1970 to 2005. We tested an environmental Kuznets curve (EKC) hypothesis and found that total CO2 emissions from nine industries show an N-shaped trend instead of an inverted U or monotonic increasing trend with increasing income. The EKC hypothesis for sector-level CO2 emissions was supported in the (1) paper, pulp, and printing industry; (2) wood and wood products industry; and (3) construction industry. We also found that emissions from coal and oil increase with economic growth in the steel and construction industries. In addition, the non-metallic minerals, machinery, and transport equipment industries tend to have increased emissions from oil and electricity with economic growth. Finally, the EKC turning point and the relationship between GDP per capita and sectoral CO2 emissions differ among industries according to the fuel type used. Therefore, environmental policies for CO2 reduction must consider these differences in industrial characteristics. © 2013 Elsevier Ltd.

Effectiveness of policy against illegal disposal of waste

Our objective is to analyze the effectiveness, against the illegal disposal of waste, of a licensing system that has been introduced in a waste management policy. We theoretically find enforcement leverage in the licensing system, and then examine the theoretical result empirically. The results suggest that extending liability to disposers, which forms the basis of the enforcement leverage, deters illegal disposal more effectively than increasing penalties for illegal disposal. We also obtain evidence of transboundary movement of illegal disposal, and find how the court determines penalties for illegal disposal.

Environmental productivity and Kuznets curve in India

As a result of India's extremely rapid economic growth, the scale and seriousness of environmental problems are no longer in doubt. Whether pollution abatement technologies are utilized more efficiently is crucial in the analysis of environmental management because it influences the cost of alternative production and pollution abatement technologies. In this study, we use state-level industry data of sulfur dioxide, nitrogen dioxide, and suspended particular matter over the period 1991-2003. Employing recently developed productivity measurement technique, we show that overall environmental productivities decrease over time in India. Furthermore, we analyze the determinants of environmental productivities and find environmental Kuznets curve type relationship existences between environmental productivity and income. Panel analysis results show that the scale effect dominates over the technique effect. Therefore, a combined effect of income on environmental productivity is negative.

The impact of mobile phone distraction on the braking behaviour of young drivers : a hazard-based duration model

Braking is a crucial driving task with a direct relationship with crash risk, as both excess and inadequate braking can lead to collisions. The objective of this study was to compare the braking profile of young drivers distracted by mobile phone conversations to non-distracted braking. In particular, the braking behaviour of drivers in response to a pedestrian entering a zebra crossing was examined using the CARRS-Q Advanced Driving Simulator. Thirty-two licensed drivers drove the simulator in three phone conditions: baseline (no phone conversation), hands-free, and handheld. In addition to driving the simulator, each participant completed questionnaires related to driver demographics, driving history, usage of mobile phones while driving, and general mobile phone usage history. The drivers were 18–26 years old and split evenly by gender. A linear mixed model analysis of braking profiles along the roadway before the pedestrian crossing revealed comparatively increased decelerations among distracted drivers, particularly during the initial 20 kph of deceleration. Drivers’ initial 20 kph deceleration time was modelled using a parametric accelerated failure time (AFT) hazard-based duration model with a Weibull distribution with clustered heterogeneity to account for the repeated measures experiment design. Factors found to significantly influence the braking task included vehicle dynamics variables like initial speed and maximum deceleration, phone condition, and driver-specific variables such as licence type, crash involvement history, and self-reported experience of using a mobile phone whilst driving. Distracted drivers on average appear to reduce the speed of their vehicle faster and more abruptly than non-distracted drivers, exhibiting excess braking comparatively and revealing perhaps risk compensation. The braking appears to be more aggressive for distracted drivers with provisional licenses compared to drivers with open licenses. Abrupt or excessive braking by distracted drivers might pose significant safety concerns to following vehicles in a traffic stream.

The influence of families on early adolescent school connectedness : evidence that this association varies with adolescent involvement in peer drinking networks

School connectedness is central to the long term well-being of adolescents, and high quality parent-child relationships facilitate school connectedness. This study examined the extent to which family relationship quality is associated with the school connectedness of pre- and early teenagers, and how this association varies with adolescent involvement in peer drinking networks. The sample consisted of 7,372 10-14 year olds recruited from 231 schools in 30 Australian communities. Participants completed the Communities that Care youth survey. A multi-level model of school connectedness was used, with a random term for school-level variation. Key independent variables included family relationship quality, peer drinking networks, and school grade. Control variables included child gender, sensation seeking, depression, child alcohol use, parent education, and language spoken at home. For grade 6 students, the association of family relationship quality and school connectedness was lower when peer drinking networks were present, and this effect was nonsignificant for older (grade 8) students. Post hoc analyses indicated that the effect for family relationship quality on school connectedness was nonsignificant when adolescents in grade 6 reported that the majority of friends consumed alcohol. The results point to the importance of familyschool partnerships in early intervention and prevention.

Application of meshfree methods to numerically simulate microscale deformations of different plant food materials during drying

Plant food materials have a very high demand in the consumer market and therefore, improved food products and efficient processing techniques are concurrently being researched in food engineering. In this context, numerical modelling and simulation techniques have a very high potential to reveal fundamentals of the underlying mechanisms involved. However, numerical modelling of plant food materials during drying becomes quite challenging, mainly due to the complexity of the multiphase microstructure of the material, which undergoes excessive deformations during drying. In this regard, conventional grid-based modelling techniques have limited applicability due to their inflexible grid-based fundamental limitations. As a result, meshfree methods have recently been developed which offer a more adaptable approach to problem domains of this nature, due to their fundamental grid-free advantages. In this work, a recently developed meshfree based two-dimensional plant tissue model is used for a comparative study of microscale morphological changes of several food materials during drying. The model involves Smoothed Particle Hydrodynamics (SPH) and Discrete Element Method (DEM) to represent fluid and solid phases of the cellular structure. Simulation are conducted on apple, potato, carrot and grape tissues and the results are qualitatively and quantitatively compared and related with experimental findings obtained from the literature. The study revealed that cellular deformations are highly sensitive to cell dimensions, cell wall physical and mechanical properties, middle lamella properties and turgor pressure. In particular, the meshfree model is well capable of simulating critically dried tissues at lower moisture content and turgor pressure, which lead to cell wall wrinkling. The findings further highlighted the potential applicability of the meshfree approach to model large deformations of the plant tissue microstructure during drying, providing a distinct advantage over the state of the art grid-based approaches.

Experimental studies on web crippling behaviour of hollow flange channel beams under two flange load cases

This paper presents the details of an experimental study of a cold-formed steel hollow flange channel beam known as LiteSteel beam (LSB) subject to web crippling under End Two Flange (ETF) and Interior Two Flange (ITF) load cases. The LSB sections with two rectangular hollow flanges are made using a simultaneous cold-forming and electric resistance welding process. Due to the geometry of the LSB, and its unique residual stress characteristics and initial geometric imperfections, much of the existing research for common cold-formed steel sections is not directly applicable to LSB. Experimental and numerical studies have been carried out to evaluate the behaviour and design of LSBs subject to pure bending, predominant shear and combined actions. To date, however, no investigation has been conducted on the web crippling behaviour and strength of LSB sections. Hence an experimental study was conducted to investigate the web crippling behaviour and capacities of LSBs. Twenty-eight web crippling tests were conducted under ETF and ITF load cases, and the ultimate web crippling capacities were compared with the predictions from the design equations in AS/NZS 4600 and AISI S100. This comparison showed that AS/NZS 4600 and AISI S100 web crippling design equations are unconservative for LSB sections under ETF and ITF load cases. Hence new equations were proposed to determine the web crippling capacities of LSBs based on experimental results. Suitable design rules were also developed under the direct strength method (DSM) format.

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.