Simulation Research on the Forming Process of Large Axles Rolled by Cross-Wedge Rolling

As a novel metal forming process, cross-wedge rolling (CWR) is widely used in the manufacture of large axles in the rail transportation industry. When the forming process of the axle is studied, its formability becomes one of the key issues in the metal forming process. This paper takes LZ50 axle steel as the research object. Through the application of ANSYS finite element simulation software, combined with previous research and literature, a dynamic simulation of the rolling process is carried out, and the stress, strain and temperature field of the axle steel in the forming process are analysed. The results show that with the deepening of rolling, the plastic deformation of the metal becomes increasingly obvious. When the finishing section is reached, the temperature on the surface and inside the rolled piece reaches relatively uniform distribution

Hot Compression Test and Microstructure Evolution in LZ50 Axle Steel

True strain-true stress curves of the LZ50 axle steel were obtained after hot compression tests had been performed on a Gleeble-3800 thermal simulator at strain rates of 0.01, 0.1, 1 and 5 s^(-1) and at deformation temperatures from 850 to 1,150 ℃. Following the data processing, the relationship between the flow stress and the deformation temperature of the material under different true strain conditions was analysed. On this basis and according to the influence of deformation factors, the constitutive equation of the Johnson-Cook flow stress model is established, and the model is modified according to the defects of the model, so that the improved model can effectively predict the mechanical behaviour in the range of high strain rates and temperatures. The dynamic material model (DMM) was used to generate the hot working diagram of the material. Through calculation and analysis, the optimum process area in terms of temperature was found to be in the range from 1,050 to 1,150 ℃ and in terms of strain rate in the rage from 1 to 5 s^(-1). Finally, the microstructure evolution of the compressed specimens under different strain rates and temperatures was studied in the metallographic analysis, which provided a theoretical basis and reference value for later damage

Systematically redesigning and optimizing the expression of _D-lactate dehydrogenase efficiently produces high-optical-purity _D-lactic acid in<i> Saccharomyces cerevisiae </i>

(D)-lactic acid ((D)-LA) is gaining increased attention as it can improve the thermostability of poly lactic acid. Acid tolerant Saccharomyces cerevisiae is a good host for (D)-LA fermentation. High catalytic efficiency of (D)-lactate dehydrogenase ((D)-LDH, EC 1.1.1.28) is crucial for the production of (D)-LA in yeast. Here, a synthetic biology approach was used to construct high-producing (D)-LA strains by redesigning and optimization of (D)-LDH expression by a combination of different promoters, terminators and (D)-LDHs. The pyruvate decarboxylase-deficient mutant strain TAMH was used as host strain for optimizing the 40 (D)-LDH expression cassettes. The TCSt strain harboring the pTCSt plasmid with the TEF1 promoter, E. coli (D)-LDH and Synth25 synthetic short terminator produced 5.8 g/L (D)-LA with an optical purity of 99.9%. The production of (D)-LA was further improved by integrating this high expression cassette into the Ty1 transposable element of the YIP-01 strain with deleted Pdc1 and Pdc6. The resulting strain YIP-pTCSt-301(CGMCC2.5726) was screened by a double enzyme-coupled system. Genomes sequencing of the strain revealed three copies of the (D)-LDH expression cassette. This strain was further improved by deleting the Jen1, Cyb2, Dld1, and Adh1 genes and the resulting strain YIP-J-C-D-A1 (CGMCC2.5783) produced 80.0 g/L (D)-LA with a yield of 0.6 g/g glucose and a volumetric productivity of 1.1 g/L/h in fed-batch fermentation under non-neutralization conditions

Reduced ATR or Chk1 Expression Leads to Chromosome Instability and Chemosensitization of Mismatch Repair–deficient Colorectal Cancer Cells

Genomic instability in colorectal cancer is categorized into two distinct classes: chromosome instability (CIN) and microsatellite instability (MSI). MSI is the result of mutations in the mismatch repair (MMR) machinery, whereas CIN is often thought to be associated with a disruption in the APC gene. Clinical data has recently shown the presence of heterozygous mutations in ATR and Chk1 in human cancers that exhibit MSI, suggesting that those mutations may contribute to tumorigenesis. To determine whether reduced activity in the DNA damage checkpoint pathway would cooperate with MMR deficiency to induce CIN, we used siRNA strategies to partially decrease the expression of ATR or Chk1 in MMR-deficient colorectal cancer cells. The resultant cancer cells display a typical CIN phenotype, as characterized by an increase in the number of chromosomal abnormalities. Importantly, restoration of MMR proficiency completely inhibited induction of the CIN phenotype, indicating that the combination of partial checkpoint blockage and MMR deficiency is necessary to trigger CIN. Moreover, disruption of ATR and Chk1 in MMR-deficient cells enhanced the sensitivity to treatment with the commonly used colorectal chemotherapeutic compound, 5-fluorouracil. These results provide a basis for the development of a combination therapy for those cancer patients