Air safety & security: Traveller perceptions post the Malaysian Air disasters

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

Treatment of Hydrothermal-Liquefaction Wastewater with Crossflow UF for Oil and Particle Removal

This study aims to evaluate the application of ceramic ultrafiltration membranes in the crossflow mode for the separation of particles and oil in water emulsions (free oil droplets and micelles) from hydrothermal-liquefaction wastewater (HTL-WW) from the hydrothermal liquefaction of municipal sewage sludge. The experiments were carried out using one-channel TiO$_{2}$ membranes with pore sizes of 30, 10 and 5 nm. The results showed that the highest stable permeability could be achieved with a membrane-pore size of 10 nm, which experienced less fouling, especially through pore blockage, in comparison to the two other pore sizes. Instead of observing an increase in the permeability, the application of a higher feed temperature as well as backwash cycles led to a clear increase in irreversible fouling due to the presence of surfactants in the HTL-WW. Among several physical and chemical cleaning methods, alkaline cleaning at pH 12 proved to be the most efficient in removing fouling and maintaining stable performance on a long-term basis. Ceramic-membrane ultrafiltration can be considered as an adequate first-stage treatment of real HTL wastewater

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