VEGF-mediated cell survival in non-small-cell lung cancer: implications for epigenetic targeting of VEGF receptors as a therapeutic approach

Aims: To evaluate the potential therapeutic utility of histone deacetylase inhibitors (HDACi) in targeting VEGF receptors in non-small-cell lung cancer. Materials & methods: Non-small-cell lung cancer cells were screened for the VEGF receptors at the mRNA and protein levels, while cellular responses to various HDACi were examined. Results: Significant effects on the regulation of the VEGF receptors were observed in response to HDACi. These were associated with decreased secretion of VEGF, decreased cellular proliferation and increased apoptosis which could not be rescued by addition of exogenous recombinant VEGF. Direct remodeling of the VEGFR1 and VEGFR2 promoters was observed. In contrast, HDACi treatments resulted in significant downregulation of the Neuropilin receptors. Conclusion: Epigenetic targeting of the Neuropilin receptors may offer an effective treatment for lung cancer patients in the clinical setting.

A new constraint programming approach for optimising a coal rail system

Because of the bottlenecking operations in a complex coal rail system, millions of dollars are costed by mining companies. To handle this issue, this paper investigates a real-world coal rail system and aims to optimise the coal railing operations under constraints of limited resources (e.g., limited number of locomotives and wagons). In the literature, most studies considered the train scheduling problem on a single-track railway network to be strongly NP-hard and thus developed metaheuristics as the main solution methods. In this paper, a new mathematical programming model is formulated and coded by optimization programming language based on a constraint programming (CP) approach. A new depth-first-search technique is developed and embedded inside the CP model to obtain the optimised coal railing timetable efficiently. Computational experiments demonstrate that high-quality solutions are obtainable in industry-scale applications. To provide insightful decisions, sensitivity analysis is conducted in terms of different scenarios and specific criteria. Keywords Train scheduling · Rail transportation · Coal mining · Constraint programming