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Lung cancer is the leading cause of cancer death worldwide. The epidermal growth factor receptor (EGFR) represents the main target for non-small cell lung cancer (NSCLC) therapy, as its overexpression or constitutive activation contributes to malignancy and correlates with poor prognosis. Our previous work demonstrated that in epithelial cells β1 integrin is required for propagating EGFR signaling from the plasma membrane to the nucleus. In this study, we silenced β1 integrin in human NSCLC A549 cells. The β1 integrin-silenced cells show a defective activation of the EGFR signaling cascade, leading to decreased in vitro proliferation, enhanced sensitivity to cisplatin and Gefitinib, impaired migration and invasive behavior. Inhibitory effects on tumor growth and on the EGFR pathway were also observed in in vivo experiments. Moreover, β1 integrin silencing increases the amount of EGFR on the cell surface, suggesting that β1 integrin is required for efficient constitutive EGFR turnover at the cell membrane. Although the rate of EGF internalization and recycling is not affected in silenced cells, EGFR signaling is recovered only by expression of the Rab-coupling protein RCP, indicating that β1 integrin sustains the endocytic machinery required for EGFR signaling. Overall, these results show that β1 integrin is an essential regulator of EGFR signaling and tumorigenic properties of lung cancer cells, and that its silencing might represent an adjuvant approach to anti-EGFR therapy. [ABSTRACT FROM AUTHOR]

This paper describes the results obtained by a computational simulation of the impact of shock waves due to explosion on a flying flexible aircraft of commercial type. An explicit three-dimensional dynamic nonlinear coupled analysis has been conducted by means of the software MSC.Dytran. A Lagrangian mesh has been used for the structural parts, and a Eulerian domain is used for the surrounding fluid. The fluid-dynamic solver uses a Eulerian approach and employs a finite volume method to discretize the governing equations. Structural elements are discretized by the Finite Element Method. The impact of the related shock waves on a simple panel and a wing box has been considered. The vibration of an aircraft as a whole, caused by its flexibility, has been analyzed. The analysis has mainly shown that the conducted investigation can be used to evaluate the loads on the aircraft for various initial positions of the explosion as well as for various amounts of the explosive charge. The method could permit a better design of the aircraft with respect to explosion phenomena and simulation of aircraft accidents, aimed at understanding their causes. [ABSTRACT FROM AUTHOR]

The radio-emitting neutron star population encompasses objects with spin periods ranging from milliseconds to tens of seconds. As they age and spin more slowly, their radio emission is expected to cease. We present the discovery of an ultra-long period radio-emitting neutron star, PSR J0901-4046, with spin properties distinct from the known spin and magnetic-decay powered neutron stars. With a spin-period of 75.88 s, a characteristic age of 5.3 Myr, and a narrow pulse duty-cycle, it is uncertain how radio emission is generated and challenges our current understanding of how these systems evolve. The radio emission has unique spectro-temporal properties such as quasi-periodicity and partial nulling that provide important clues to the emission mechanism. Detecting similar sources is observationally challenging, which implies a larger undetected population. Our discovery establishes the existence of ultra-long period neutron stars, suggesting a possible connection to the evolution of highly magnetized neutron stars, ultra-long period magnetars, and fast radio bursts., Competing Interests: Conflict of interest/Competing interests The authors declare no competing interests.