Towards a common measure of greenhouse gas related logistics activity using data envelopment analysis

Monitoring company emissions from freight transport is essential if future greenhouse gas (GHG) reductions are to be realised. Modern economies are characterised increasingly by lower density freight movements. However, weight-based measures of freight transport activity (tonne-kilometre, tonnes lifted) are not good at describing volume-limited freight. After introducing the need for performance measurement, the problem of benchmarking is outlined in more detail. A context-dependent undesirable output data envelopment analysis (DEA) model, designed to be sensitive to business context, is then tested on a simulated set of fleet profiles. DEA can produce more consistent measures of good-practice, compared to ratio-based key performance indicators (KPI), providing emission reduction targets for companies and an aggregate reporting tool

Congenital deficiency reveals critical role of ISG15 in skin homeostasis

Ulcerating skin lesions are manifestations of human ISG15 deficiency, a type I interferonopathy. However, chronic inflammation may not be their exclusive cause. We describe two siblings with recurrent skin ulcers that healed with scar formation upon corticosteroid treatment. Both had a homozygous nonsense mutation in the ISG15 gene, leading to unstable ISG15 protein lacking the functional domain. We characterized ISG15(-/-) dermal fibroblasts, HaCaT keratinocytes, and human induced pluripotent stem cell-derived vascular endothelial cells. ISG15-deficient cells exhibited the expected hyperinflammatory phenotype, but also dysregulated expression of molecules critical for connective tissue and epidermis integrity, including reduced collagens and adhesion molecules, but increased matrix metalloproteinases. ISG15(-/-) fibroblasts exhibited elevated ROS levels and reduced ROS scavenger expression. As opposed to hyperinflammation, defective collagen and integrin synthesis was not rescued by conjugation-deficient ISG15. Cell migration was retarded in ISG15(-/-) fibroblasts and HaCaT keratinocytes, but normalized under ruxolitinib treatment. Desmosome density was reduced in an ISG15(-/-) 3D epidermis model. Additionally, there were loose architecture and reduced collagen and desmoglein expression, which could be reversed by treatment with ruxolitinib/doxycycline/TGF-beta 1. These results reveal critical roles of ISG15 in maintaining cell migration and epidermis and connective tissue homeostasis, whereby the latter likely requires its conjugation to yet unidentified targets

High-Throughput Screening for Modulators of CFTR Activity Based on Genetically Engineered Cystic Fibrosis Disease-Specific iPSCs

Organotypic culture systems from disease-specific induced pluripotent stem cells (iPSCs) exhibit obvious advantages compared with immortalized cell lines and primary cell cultures, but implementation of iPSC-based high-throughput (HT) assays is still technically challenging. Here, we demonstrate the development and conduction of an organotypic HT Cl/I exchange assay using cystic fibrosis (CF) disease-specific iPSCs. The introduction of a halide-sensitive YFP variant enabled automated quantitative measurement of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) function in iPSC-derived intestinal epithelia. CFTR function was partially rescued by treatment with VX-770 and VX-809, and seamless gene correction of the p.Phe508del mutation resulted in full restoration of CFTR function. The identification of a series of validated primary hits that improve the function of p.Phe508del CFTR from a library of 42,500 chemical compounds demonstrates that the advantages of complex iPSC-derived culture systems for disease modeling can also be utilized for drug screening in a true HT format

Efficient and versatile CRISPR engineering of human neurons in culture to model neurological disorders

The recent identification of multiple new genetic causes of neurological disorders highlights the need for model systems that give experimental access to the underlying biology. In particular, the ability to couple disease-causing mutations with human neuronal differentiation systems would be beneficial. Gene targeting is a well-known approach for dissecting gene function, but low rates of homologous recombination in somatic cells (including neuronal cells) have traditionally impeded the development of robust cellular models of neurological disorders. Recently, however, CRISPR/Cas9 gene editing technologies have expanded the number of systems within which gene targeting is possible. Here we adopt as a model system LUHMES cells, a commercially available diploid human female mesencephalic cell line that differentiates into homogeneous mature neurons in 1-2 weeks. We describe optimised methods for transfection and selection of neuronal progenitor cells carrying targeted genomic alterations using CRISPR/Cas9 technology. By targeting the endogenous X-linked MECP2 locus, we introduced four independent missense mutations that cause the autism spectrum disorder Rett syndrome and observed the desired genetic structure in 3-26% of selected clones, including gene targeting of the inactive X chromosome. Similar efficiencies were achieved by introducing neurodevelopmental disorder-causing mutations at the autosomal EEF1A2 locus on chromosome 20. Our results indicate that efficiency of genetic “knock-in” is determined by the location of the mutation within the donor DNA molecule. Furthermore, we successfully introduced an mCherry tag at the MECP2 locus to yield a fusion protein, demonstrating that larger insertions are also straightforward in this system. We suggest that our optimised methods for altering the genome of LUHMES cells make them an attractive model for the study of neurogenetic disorders

Airlines-within-airlines: A business model moving East

Low-cost carriers (LCCs) are a significant threat to the sustainability of network airlines. That LCCs are growing – particularly within Asia-Pacific – exacerbates this problem and network airlines have reacted to this by creating lower-cost subsidiaries, known as airlines-within-airlines (AWAs). The purpose of this paper is to determine the necessary criteria for successful AWAs while updating analysis of past, present, and proposed and announced AWAs. For this, we revisit existing literature and airline data, mainly from annual reports, from such AWAs. Initial results indicate that AWAs have limited success, with 27 failures of an identified 67, although only three in Asia-Pacific. Of those presently operating, 58.1% are from Asia-Pacific with this region containing 40.0% of the proposed and announced carriers. In our view it is ill-defined strategies, late market entrance, excessive management control, insufficient dissimilarity from the parent, higher costs and less efficiency vis-à-vis low-cost competitors, and operating within highly competitive markets with excess capacity and comparatively low fares that are key reasons for failure. In contrast, the most successful AWAs have considerable autonomy from their parent, market dominance, decisive leadership, and less deviation from the pure LCC model unless a sufficient revenue premium is achieved

A non-parametric efficiency measure incorporating perceived airline service levels and profitability

Customer service influences satisfaction, loyalty, repeat business, and hence potentially profitability. This paper investigates whether airline customer service impacts upon the profitability of airlines (the top 150 worldwide). As our results suggest that this impact is limited, we then apply DEA models and develop, for the first time, a single-efficiency measure that combines the typical airline targets of maximisation of RPKs, customer satisfaction, and profitability. We further use second-stage truncated regressions and show that only the share of cabin crew (but neither fleet age nor LCC operation) has a significant impact on overall airline efficiency

International air travel: Safety and security in a post-MH climate

© 2015 ATRF, Commonwealth of Australia. All rights reserved. Air transport is of substantial importance to economies, societies and freedom as it connects businesses and individuals with the world. However, two recent Malaysia Airlines incidents have resulted in even more security measures at airports and have anecdotally changed the security and safety perceptions of the traveling (or no longer traveling) public. Our study investigates for the first time attitudes towards air travel, safety and security and determines empirically if travellers are willing to experience even more invasive security measures in light of these tragedies. Our results suggest that there is a latent demand for air services despite the recent of the Malaysian Airline tragedies. Out of our proposed measures the presence of visible uniformed police creates the greatest feeling of security and it is seen as important to better communicate what security operations do and why it is effective in threat minimisation. We find willingness to pay for avoiding additional incidents both in terms of money and time but respondents are also willing to pay more to speed up the security process. Our results also suggest there is no desire to accept security processes that invade privacy considerably more what is currently practiced. We conclude that with respect to air travel the magnitude of trade-of between personal freedoms for improved security is limited. Travellers appear willing to accept risks, or perceive them as isolated and limited to airlines with inferior safety records and/or destinations with inferior security records

Exploring Perceived Safety, Privacy, and Distrust on Air Travel Choice in the Context of Differing Passenger Screening Procedures

© 2017, © The Author(s) 2017. This article examines perceptions of how safe airline travel is and respondents’ level of concern over privacy and trust of authorities. These attitudes are then used to understand the choice to travel under passenger screening processes with differing levels of invasiveness. We find that travelers who are more trusting of authorities are more likely to choose to travel internationally, whereas those with low overall feelings of safety while onboard an aircraft are predisposed to not travel. Our analysis reveals what attitudes and potential screening measures are linked to this feeling of overall safety, chief among which is the presence of visible uniformed police. Our results are also novel as they study these attitudes in the context of a spate of recent air-related disasters; finding no desire to accept screening processes that invade privacy beyond what is currently practiced