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Laser shock hole-clinching is a novel mechanical joining process in which the shock wave pressure induced by a high-energy pulsed laser is employed as a punch. This process is quite suitable for the joining of two dissimilar materials with significant differences in plasticity and strength. However, the effect of key process parameters on the forming quality of joints by laser shock hole-clinching is less concerned. In this study, the influence of laser power density, spacer height, number of laser pulse, and initial grain size of metal foils on the forming quality of Cu-Fe joints was experimentally investigated. The characteristics of interlock value and thinning rate distribution under various process parameters were systematically examined. It is revealed that laser shock hole-clinching process can be divided into the confined bulging and interlock formation stages. Based upon the examination of substandard joints, the defects in laser shock hole-clinching process are classified which contains no interlock, nonuniform interlock, bottom and neck fracture. It is found that the thinnest position of joints locates at the region in contact with the upper corner of the joining partner II in which extensive plastic deformation occurs related to the force acting during clinching process. The interlock value increases significantly as the enlargement of initial grain size, whereas the deviation also becomes larger due to the inhomogeneous plastic deformation for the metal foil with coarse grains. Moreover, the ratio of spacer height to the thickness of the joining partner II affects the thinning rate distribution and interlock value of joints. The spacer height equaling to the thickness of the joining partner II is recommended within the given parameters. [ABSTRACT FROM AUTHOR]

Introduction: Mutated tumor suppressor genes (TSG) such as TP53, STK11, and MGA are widely-reported. We hypothesized the presence of single mutation or co-occurring mutations in these specific genes may represent a significant therapeutic target for lung adenocarcinoma.Methods: We sequenced lung adenocarcinoma samples from 677 East-Asian patients, combined them with those from cBioPortal public database (including TCGA) and performed a comparative analysis between Asian and Caucasian populations.Results: East-Asian lung adenocarcinomas presented distinct driver-mutational distribution compared to that of Caucasians (79% vs 56%, p < 0.001). Similar results were observed in TSG mutations of TP53 (35% vs 46%, p = 0.150), STK11 (4% vs 17%, p = 0.006) and MGA (10% vs 4%, p = 0.166). Compared with none-mutational cases, the patients harboring TSG mutations are more likely to be male (p = 0.009), smokers (p < 0.001), and more advanced disease (p = 0.004). In addition, the TSG-mutated tumors had poorer differentiation (p < 0.001), and more likely to be solid or micropapillary-predominant adenocarcinomas (p < 0.001). Survival analysis showed that both overall survival (OS, p < 0.001) and post-recurrence survival (PRS, p < 0.001) became worse with the accumulation of TSG mutations. However, the prognostic variety was not found in Caucasian patients. Moreover, multivariate analysis proved the accumulation of TSG mutations independently predicts both unfavorable OS (HR = 0.435, 95% CI 0.245-0.774, p = 0.005) and PRS (HR = 0.491, 95% CI 0.269-0.894, p = 0.020) in East-Asian patients, adjusting all other survival-associated factors.Conclusions: Co-occurring mutations of specific TSGs define unfavorable subgroups of lung adenocarcinoma, implying that the tumor promotion mechanisms contribute to the heterogeneity in tumor evolution. However, the Caucasian population did not show the same results, providing insights into the molecular basis underlying the striking racial disparities of this disease and evidence for different gene-panel designs for different population in the purpose of targeted therapy. [ABSTRACT FROM AUTHOR]

Introduction: Evidence shows that exon 19 deletions (19del) and exon 21 Leu858Arg point mutation (L858R) of EGFR are different in response to EGFR tyrosine kinase inhibitor (EGFR-TKI) therapy in advanced lung cancers. However, the impact of the two mutational types in the early stage lung adenocarcinoma is unknown. Methods: We enrolled consecutive patients with operable adenocarcinoma which harbored 19del or L858R to investigate the clinicopathologic characteristics and prognostic outcomes. Results: Between 2008 and 2013, a total of 607 patients with 19del (47.9%) or L858R (52.1%) were included in this study. Clinicopathologic and disease-associated factors were well-balanced between 19del and L858R patients. Both recurrence-free survival (5-year RFS: 37.9% vs. 42.9%, p = 0.075) and overall survival (5-year OS: 64.7% vs. 60.7%, p = 0.741) were similar between the two groups. After relapse, 19del was associated with a better post-recurrence survival (PRS) than L858R ( p = 0.016). Multivariate analysis demonstrated that mutational types (HR = 1.521, 95% CI: 1.106-2.093, p = 0.01) and tyrosine kinase inhibitors (TKI) use after recurrence (HR = 0.422, 95% CI: 0.301-0.592, p < 0.001) were independent predictors of PRS. The 19del and L858R patients were similar regarding recurrent patterns, except on pleural/chest wall metastasis (26.0% vs. 12.2%, p = 0.007). Conclusions: Patients with the early stage lung adenocarcinoma harboring either 19del or L858R share similar RFS and OS. After recurrence, both could benefit from TKI therapy without the need for a second biopsy, but 19del seemed to be associated with better PRS. [ABSTRACT FROM AUTHOR]

Laser shock hole-clinching is a high–strain rate mechanical joining process in which the metal foils are joined together based on plastic deformation generated by a laser-induced shock wave. In the process, fracture is a typical defect and seriously influences the clinching quality and production efficiency of joints. However, the classification and variation of fracture modes in laser shock hole-clinching are of less concern. In this study, the fracture mode of Cu-Fe joints in laser shock hole-clinching was experimentally investigated. Both optical microscopy and scanning electron microscopy were adopted to analyze the fracture surface morphology of clinched joints. The influence of laser power density, laser spot diameter, the initial grain size and thickness of metal foil, and spacer height on the fracture mode of joints was evaluated. It is revealed that the temperature increase caused by high–strain rate plastic deformation has no impact on the fracture behavior of the joining partners. Fracture always occurs on joining partner I, and it can be divided into four modes, including bottom surface fracture, bottom corner fracture, neck fracture, and mixed fracture. It is found that fracture on the bottom surface is seldom seen but mixed fracture accounts for most of the cracked specimens. Neck tensile fracture rarely appears alone, and it usually exists accompanied by fracture on the bottom corner. The fracture mode varies from a tensile fracture mode on the bottom corner to a mixed fracture mode and then to a shear fracture mode on the neck with the enhancement of laser power density. In addition, the initial grain size of joining partner I has a significant impact on the fracture mode of clinched joints. The fracture mode varies from bottom corner fracture to mixed fracture in relation to the change of mechanical properties of metal foil with an enlarged grain size. However, the mixed fracture mode always appears with the enlargement of both laser spot diameter and spacer height. [ABSTRACT FROM AUTHOR]