In the field of underwater emergency maintenance, submarine pipeline cutting is generally performed by a diamond wire saw. The process, in essence, involves diamond grits distributed on the surface ...of the beads cutting X56 pipeline steel bit by bit at high speed. To find the effect of the different parameters (cutting speed, coefficient of friction and depth of cut) on cutting force, the finite element (FEA) method and response surface method (RSM) were adopted to obtain cutting force prediction models. The former was based on 64 simulations; the latter was designed according to DoE (Design of Experiments). Confirmation experiments were executed to validate the regression models. The results indicate that most of the prediction errors were within 10%, which were acceptable in engineering. Based on variance analyses of the RSM models, it could be concluded that the depth of the cut played the most important role in determining the cutting force and coefficient the of friction was less influential. Despite making little direct contribution to the cutting force, the cutting speed is not supposed to be high for reducing the coefficient of friction. The cutting force models are instructive in manufacturing the diamond beads by determining the protrusion height of the diamond grits and the future planning of the cutting parameters.
Abstract Measuring the flatness error of large precision workpieces quickly and accurately is a difficult problem. A new method for preprocessing flatness measurement data based on MSE (mean squared ...error) is proposed. A mathematical model of a new data preprocessing method was established, and the mathematical formula for model solving was derived in detail. The data were measured by digital level on the plane of the granite base with dimensions of 2340 m×1540 mm. The new method and SmartLevel (basic measurement system of the level computer) were used to calculate and process the data. The flatness errors after diagonal evaluation were 4.07 μm and 3.90 μm, respectively. The relative error of the two was 4.36%, which confirmed the reliability and accuracy of the new method. The data results show that this method can be effectively used for the engineering measurement of the flatness of large precision workpieces.
Cancer stem cells (CSCs) contribute to therapy resistance in HCC. Linear ubiquitin chain assembly complex (LUBAC) has been reported to accelerate the progression of cancers, yet its role in the ...sorafenib response of HCC is poorly defined. Herein, we investigated the impact of LUBAC on sorafenib resistance and the CSC properties of HCC, and explored the potential targeted drugs.
We found that HOIL-1, but not the other components of LUBAC, played a contributing role in LUBAC-mediated HCC sorafenib resistance, independent of its ubiquitin ligase activity. Both in vitro and in vivo assays revealed that the upregulated HOIL-1 expression enhanced the CSC properties of HCC. Mechanistically, HOIL-1 promoted sorafenib resistance and the CSC properties of HCC through Notch1 signaling. Mass spectrometry, co-immunoprecipitation, western blot, and immunofluorescence were used to determine that the A64/Q65 residues of HOIL-1 bound with the K78 residue of Numb, resulting in impaired Numb-mediated Notch1 lysosomal degradation. Notably, pixantrone was screened out by Autodock Vina, which was validated to disrupt HOIL-1/Numb interaction to inhibit Notch1 signaling and CSC properties by targeting the Q65 residue of HOIL-1. Moreover, pixantrone exerted synergistic effects with sorafenib for the treatment of HCC in different HCC mouse models.
HOIL-1 is critical in promoting sorafenib resistance and CSC properties of HCC through Notch1 signaling. Pixantrone targeting HOIL-1 restrains the sorafenib resistance and provides a potential therapeutic intervention for HCC.
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