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To overcome the shortcomings of current technologies for meso-scale manufacturing such as MEMS and ultra precision machining, this paper focuses on the investigations on the meso milling process with a miniaturized machine tool. First, the related technologies for the process mechanism studies are investigated based on the analysis of the characteristics of the meso milling process. An overview of the key issues is presented and research approaches are also proposed. Then, a mesoscale milling machine tool system is developed. The subsystems and their specifications are described in detail. Finally, some tests are conducted to evaluate the performance of the system. These tests consist of precision measurement of the positioning subsystem, the test for machining precision evaluation, and the experiments for machining mechanical parts with complex features. Through test analysis, the meso milling process with a miniaturized machine tool is proved to be feasible and applicable for meso manufacturing.

A sub-cycling integration algorithm (or named multi-time-steps integration algorithm), which has been successfully applied to FEM dynamical analysis, was firstly presented by Belytschko et al. (Comput Methods Appl Mech Eng 17/18:259-275, 1979). However, the problem of how to apply this type of algorithm to flexible multi-body dynamics (FMD) problems still lacks investigation up to now. Similar to the region-partitioning method used in FEM, this paper presents a central-difference-based sub-cycling integral method by decomposing the variables of an FMD equation into several groups and adopting different integral step sizes to each group of the variables. Based on the condensed form of an FMD equation, a group of common update formulae and a sub-step update formula, which constitute the sub-cycling together, are established in the paper. Furthermore, an implementation flowchart of the sub-cycling is presented. Stability of the sub-cycling will be analyzed and numerical examples will be performed to verify availability and precision of the sub-cycling in part II of the paper.

It has been documented that Helicobacter hepaticus (H. hepaticus) infection is linked to chronic hepatitis and fibrosis in male BALB/c mice. However, the mechanism underlying the mice model of H. hepaticus–induced hepatocellular carcinoma is not fully known. In this study, male BALB/c mice were infected with H. hepaticus for 3, 6, 12, and 18 months. H. hepaticus colonization, histopathology, expression of proinflammatory cytokines, key signaling pathways, and protein downstream high-mobility group box-1 (HMGB1) in the liver were examined. Our data suggested that the H. hepaticus colonization level in the colon and liver progressively increased over the duration of the infection. H. hepaticus–induced hepatic inflammation and fibrosis were aggravated during the infection, and hepatic preneoplasia developed in the liver of infected mice at 12 and 18 months post-inoculation (MPI). H. hepaticus infection increased the levels of alanine aminotransferase and aspartate aminotransferase in the infected mice. In addition, the mRNA levels of IL-6, Tnf-α, Tgf-β, and HMGB1 were significantly elevated in the liver of H. hepaticus–infected mice from 3 to 18 MPI as compared to the controls. In addition, Ki67 was increased throughout the duration of the infection. Furthermore, HMGB1 protein was activated and translocated from the nucleus to the cytoplasm in the hepatocytes and activated the proteins of signal transducers and activators of transcription 3 (Stat3) and mitogen-activated protein kinase (MAPK) [extracellular regulated protein kinases 1/2 (Erk1/2) and mitogen-activated protein kinase p38 (p38)] upon H. hepaticus infection. In conclusions, these data demonstrated that male BALB/c mice infected with H. hepaticus are prone to suffering hepatitis and developing into hepatic preneoplasia. To verify the effect of HMGB1 in the progression of liver preneoplasia, mice were infected by H. hepaticus for 2 months before additional HMGB1 recombinant adenovirus treatment. All mice were sacrificed at 4 MPI, and the sera and liver tissues from all of the mice were collected. Immunology and histopathology evaluation showed that HMGB1 knockdown attenuated the H. hepaticus–induced hepatic and fibrosis at 4 MPI. Therefore, we showed that H. hepaticus–induced liver preneoplasia is closely correlated with the activation and accumulation of HMGB1.