According to the Hugenholtz-Van Hove theorem, nuclear symmetry energy E sym (ρ) and its slope L(ρ) at an arbitrary density ρ are determined by the nucleon isovector (symmetry) potential U sym (ρ, k) and its momentum dependence ∂Usym ∂k . The latter determines uniquely the neutron-proton effective k-mass splitting m *in neutron-rich nucleonic matter of isospin asymmetry δ. Using currently available constraints on the E sym (ρ 0 ) and L(ρ 0 ) at normal density ρ 0 of nuclear matter from 28 recent analyses of various terrestrial nuclear laboratory experiments and astrophysical observations, we try to infer the corresponding neutron-proton effective k-mass splitting m * n−p (ρ 0 , δ). While the mean values of the m * n−p (ρ 0 , δ) obtained from most of the studies are remarkably consistent with each other and scatter very closely around an empirical value of m * n−p (ρ 0 , δ) = 0.27 · δ, it is currently not possible to scientifically state surely that the m * n−p (ρ 0 , δ) is positive within the present knowledge of the uncertainties. Quantifying, better understanding and then further reducing the uncertainties using modern statistical and computational techniques in extracting the E sym (ρ 0 ) and L(ρ 0 ) from analyzing the experimental data are much needed.

Tyrosine kinases (TKs) are prominent targets in cancer therapies, and more than 30 TK inhibitors have been approved for treatments in tumors with abnormal TK. Disappointingly, an incomplete response can occur with the long-term use of TK inhibitors, known as cancer drug resistance, which can be caused by kinome reprogramming. Hence, monitoring the status of TKs is crucial for revealing the underlying drug resistance mechanism. Here, we describe a TK activity-representing peptide library-based multiple reaction monitoring (TARPL-MRM) strategy for directly inferring TK activities. The strategy facilitated the assay of 87 human TKs through target quantification of 301 phosphorylation sites. Using this strategy, we demonstrated the heterogeneity of TK activity in different non-small cell lung cancer (NSCLC) cell lines and assessed the response of TK activities to the EGFR inhibitor AZD9291 in NSCLC cells. We found that the acquired resistance of H1975 cells to AZD9291 requires SRC activity, and inhibition of SRC plays potential roles in overcoming this resistance. In summary, our work reveals that this strategy has the potential to become a powerful tool for TK studies, clinical diagnostics, and the discovery of new therapeutic targets.

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are the most important chemotherapeutics for non-small-cell lung cancer (NSCLC) therapy. The resistance to EGFR-TKIs is one of the biggest obstacles to NSCLC outcome. In this study, taking advantage of phospho- and proximal proteomic techniques, we analyzed the network rearrangement in cell lines responding to AZD9291 treatment and found that cell-cell adhesion was dramatically enhanced in AZD9291-resistant cells. Further analysis revealed that protein tyrosine kinase 7 (PTK7) expression was significantly elevated. Knockdown or overexpression assays showed that PTK7 played a critical role in improving cell adhesion, which enhanced drug resistance. Because PTK7 is a membrane-localized pseudokinase, the proximal labeling probe BirA* was fused to reveal PTK7-interacting proteins. We found that PTK7 interacted with and stabilized NDRG1, which is located predominantly adjacent to adherens junctions. Downregulation of PTK7 or NDRG1 eliminated the resistance of H1975-resistant (H1975-R) and PC9-resistant (PC9-R) cells to AZD9291, suggesting that the PTK7-NDRG1 axis might be a potential target to eliminate the EGFR-TKI resistance during NSCLC therapy.

The purpose of this paper is to develop clinching technology using AC servo direct-drive device. The control systems of AC servo direct-drive device are designed to control the clinching. It could accurately control the connection of aluminum alloy 6061 sheets with the round joint. The joint quality is evaluated by the tensile tests. The results of the tensile tests shown that fracture load satisfied the required joint strength. Meanwhile, AC servo direct-drive device also could ensure the efficiency and quality of clinching process.

Base on clinching process, an air-hydraulic intensifier clinching devices was designed. In order to accurately control the quality of clinching, the displacement sensor and pressure sensor were joined in the control loop. So two different control feedback loops were founded. With two different ways of clinching tests, a clinching test method was founded, and the joint strength is analyzed. The result was that the shears strength and fracture strength in different directions of clinching samples are different.