Epsilon Flock: a model migration language

Model-driven engineering introduces additional challenges for controlling and managing software evolution. Today, tools exist for generating model editors and for managing models with transformation, validation, merging and weaving. There is limited support, however, for model migration—a development activity in which instance models are updated in response to metamodel evolution. In this paper, we propose conservative copy—a style of model transformation that we believe is well-suited to model migration—and Epsilon Flock—a compact model-to-model transformation language tailored for model migration. The proposed structures are evaluated by comparing the conciseness of model migration strategies written in different styles of transformation language, using several examples of evolution taken from UML and the graphical modelling framework.     

The Influence of Governance on the Provision of Urban Environmental Infrastructure and Services for Low-income Groups

This paper describes the inadequacies in the provision for water, sanitation and solid waste collection in nine cities in Africa, Asia and Latin America and discusses the main explanatory factors. These include the quality and capacity of each city's local government, and the nature of its relationship with citizen groups and non-governmental organizations within the city and with governments at provincial/state or national level. The paper highlights the many political constraints on ensuring healthier living and working environments for lower-income groups, including those rooted in local government structures and perceptions, as well as those related to low per capita incomes and poor economic performance.     

The effect of filters and collimators on Compton scatter and Pb K-series peaks in XRF bone lead analysis

The utility of Al, Cu and In filters and collimators of different diameters in the X-ray fluorescence measurement of lead in the bone was investigated. The changes in Compton scattering and Pb K-series peaks were analyzed with different filters and collimators. Compton scattering and fractional dead time were significantly reduced with the use of filters. The FWHM values of Pb Kα₁, Kβ_1,3 peaks decrease in a nearly linear relation with the ratio of length of collimator to the diameter as the small diameter collimator with long length reduces divergence of spectra, thus improves resolution. The measurement precisions of Kα₁ and Kβ_1,3 peaks were improved by applying an indium filter. The ratio of signal-to-noise slightly increases when an indium filter was used.     

Management of stream compensation for a large conjunctive use scheme,Shropshire, UK

The Shropshire Groundwater Scheme (SGS) is the largest conjunctive use scheme in the United Kingdom. The SGS operates in drought periods, pumping water from the Permo‐Triassic Sandstone aquifer in Shropshire, England to regulate flows in the River Severn, alongside releases from conventional surface water reservoirs. This regulation protects the environment and increases the security of supply of major public water supply abstractions downstream. An important operational consideration is the impact SGS groundwater abstraction has on small streams that rise on the Shropshire Permo‐Triassic Sandstone. Compensation boreholes have been installed to maintain flows during and after the operation of the SGS. This paper shows how a groundwater model of the East Shropshire Permo‐Triassic Sandstone has been used to estimate the required level of compensation flows for recent climatic conditions to optimise the use of the SGS. The catchment wide conditions are included in this analysis by using the results of a large‐scale surface water model of the River Severn.     

Review Essay

Book reviewed: Christopher C. Sellers, The Trials of Developing the ‘Social’ With the ‘Science’: A Review Essay of Hazards of the Job: From Industrial Disease to Environmental Health Science     

Carfilzomib Promotes the Unfolded Protein Response and Apoptosis in Cetuximab-Resistant Colorectal Cancer

Cetuximab is a common treatment option for patients with wild-type K-Ras colorectal carcinoma. However, patients often display intrinsic resistance or acquire resistance to cetuximab following treatment. Here we generate two human CRC cells with acquired resistance to cetuximab that are derived from cetuximab-sensitive parental cell lines. These cetuximab-resistant cells display greater in vitro proliferation, colony formation and migration, and in vivo tumour growth compared with their parental counterparts. To evaluate potential alternative therapeutics to cetuximab-acquired-resistant cells, we tested the efficacy of 38 current FDA-approved agents against our cetuximab-acquired-resistant clones. We identified carfilzomib, a selective proteosome inhibitor to be most effective against our cell lines. Carfilzomib displayed potent antiproliferative effects, induced the unfolded protein response as determined by enhanced CHOP expression and ATF6 activity, and enhanced apoptosis as determined by enhanced caspase-3/7 activity. Overall, our results indicate a potentially novel indication for carfilzomib: that of a potential alternative agent to treat cetuximab-resistant colorectal cancer.     

EPLIN,a Putative Tumour Suppressor in Colorectal Cancer,Implications in Drug Resistance

Colorectal cancer is a serious threat to human health. Poor prognosis and frequently reported drug resistance urges research into novel biomarkers and mechanisms to aid in the understanding of the development and progression of colorectal cancer and to optimise therapeutic strategies. In the current study, we investigated the roles of a putative tumour suppressor, EPLIN, in colorectal cancer. Our clinical colorectal cancer cohort and online databases revealed a downregulation of EPLIN in colorectal cancer tissues compared with normal tissues. The reduced expression of EPLIN was associated with poor clinical outcomes of patients. In vitro cellular function assays showed that EPLIN elicited an inhibitory effect on cellular growth, adhesion, migration and invasion. Utilising a protein microarray on protein samples from normal and tumour patient tissues suggested HSP60, Her2 and other signalling events were novel potential interacting partners of EPLIN. It was further revealed that EPLIN and HSP60 were negative regulators of Her2 in colorectal cancer cells. The clinical cohort also demonstrated that expression of HSP60 and Her2 affected clinical outcomes, but most interestingly the combination of EPLIN, HSP60 and Her2 was able to identify patients with the most unfavourable clinical outcome by independently predicting patient overall survival and disease free survival. Furthermore, EPLIN and HSP60 exhibited potential to regulate cellular response to chemotherapeutic and EGFR/Her2 targeted therapeutic agents. In conclusion, EPLIN is an important prognostic factor for patients with colon cancer and reduced EPLIN in CRC contributes to aggressive traits of CRC cells and their responses to chemotherapeutic drugs. Collectively, EPLIN is a pivotal factor for the development and progression of colorectal cancer and has important clinical and therapeutic values in this cancer type.     

The lantibiotic lacticin 3147 produced in a milk-based medium improves the efficacy of a bismuth-based teat seal in cattle deliberately infected with Staphylococcus aureus

A preparation of the bacteriocin lacticin 3147 (prepared from a demineralized whey protein fermentation liquor) was combined as a powder with a bismuth-based intramammary teat seal and evaluated for its potential as an antimicrobial in non-lactating cows. The lacticin/teat seal formulation enabled significant bacteriocin release from the seal without the requirement for a surfactant. Studies in vivo in lactating cows demonstrated that this formulation was effective in reducing bacterial recoveries (approximately 20-fold) from teats deliberately inoculated with Staphylococcus aureus after infusion. Moreover, this formulation also significantly reduced the numbers of Staph. aureus recovered from teats that were exposed to the challenge bacterium before the infusion of the teat seal preparation. The powdered preparation of lacticin 3147 did, however, cause some teat irritation as evidenced by associated rises in somatic cell count (SCC). However, this effect was short-lived and when the mean SCC readings pre-infusion and the final two readings post-infusion were compared, there was no significant difference in the immunological acceptance between treatments.