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Zr-based bulk metallic glass is an amorphous alloy. In order to study the burr problem in the groove milling process of Zr-based bulk metallic glass, the milling force in the process is studied experimentally. Then the effect of milling parameters on the burr of Zr-based bulk metallic glass was studied, and the relationship between milling force and burr was analyzed. In order to further study the milling burr of amorphous alloy, under the same test parameters, the single crystal alloy material (nickel base single crystal superalloy DD5) and the traditional polycrystalline metal material (304 stainless steel) were selected for comparative test and analysis. The results show that Zr-based bulk metallic glass has good groove milling machinability. The test results provide some experimental basis for groove milling of Zr-based bulk metallic glass. [ABSTRACT FROM AUTHOR]

In order to study the milling machinability of Zr-based bulk metallic glass, a comparative experimental study on the surface roughness of the milling groove bottom surface for Zr-based bulk metallic glass was carried out in this paper. Through different processing materials, milling tools with different coatings, milling tools with different geometric parameters, and different processing conditions, a large number of comparative tests were carried out on the surface roughness of the milling groove bottom surface for Zr-based bulk metallic glass. The surface roughness values of the milling groove bottom surface are compared, studied, and analyzed from many angles (surface roughness Sa, Sq, Sz, Ssk, and Sku). The test results show that Zr-based bulk metallic glass has good milling machinability. It can obtain a low surface roughness value through the processing conditions and methods used in the test. The research content of this paper provides experimental basis for groove milling of Zr-based bulk metallic glass. At the same time, it also provides a strong test basis for the manufacture of Zr-based bulk metallic glass parts. [ABSTRACT FROM AUTHOR]

Background: Intrahepatic cholestasis of pregnancy (ICP) can cause premature delivery and stillbirth. Previous studies have reported that mutations in ABC transporter genes strongly influence the transport of bile salts. However, to date, their effects are still largely elusive.Methods: A whole-exome sequencing (WES) approach was used to detect novel variants. Rare novel exonic variants (minor allele frequencies: MAF < 1%) were analyzed. Three web-available tools, namely, SIFT, Mutation Taster and FATHMM, were used to predict protein damage. Protein structure modeling and comparisons between reference and modified protein structures were performed by SWISS-MODEL and Chimera 1.14rc, respectively.Results: We detected a total of 2953 mutations in 44 ABC family transporter genes. When the MAF of loci was controlled in all databases at less than 0.01, 320 mutations were reserved for further analysis. Among these mutations, 42 were novel. We classified these loci into four groups (the damaging, probably damaging, possibly damaging, and neutral groups) according to the prediction results, of which 7 novel possible pathogenic mutations were identified that were located in known functional genes, including ABCB4 (Trp708Ter, Gly527Glu and Lys386Glu), ABCB11 (Gln1194Ter, Gln605Pro and Leu589Met) and ABCC2 (Ser1342Tyr), in the damaging group. New mutations in the first two genes were reported in our recent article. In addition, compared to the wild-type protein structure, the ABCC2 Ser1342Tyr-modified protein structure showed a slight change in the chemical bond lengths of ATP ligand-binding amino acid side chains. In placental tissue, the expression level of the ABCC2 gene in patients with ICP was significantly higher (P < 0.05) than that in healthy pregnant women. In particular, the patients with two mutations in ABC family genes had higher average values of total bile acids (TBA), aspartate transaminase (AST), direct bilirubin (DBIL), total cholesterol (CHOL), triglycerides (TG) and high-density lipoprotein (HDL) than the patients who had one mutation, no mutation in ABC genes and local controls.Conclusions: Our present study provide new insight into the genetic architecture of ICP and will benefit the final identification of the underlying mutations. [ABSTRACT FROM AUTHOR]