Longitudinal Deformation of Deep Shield Tunnels Caused by Upper Load Reduction.

Above-crossing excavations may cause uplift damages on existing shield tunnels. Therefore, to accurately calculate the deformation of shield tunnels is very necessary for geotechnical engineers. At present, the single-sided elastic foundation beam model is usually used in longitudinal deformation calculations for shield tunnels, which overestimates the uplift of deep shield tunnels. Because of the existence of the ground arch, deep shield tunnels are subjected to two-sided foundation reaction forces. Therefore, this paper proposes a partial missing double-sided elastic foundation beam model and the related fourth-order partial differential equations. In this model, the shield tunnel is subjected to double Winkler foundation springs and is simply considered a Euler-Bernoulli beam. A two-stage analysis method is used to solve the problem. First, the vertical unloading stress due to the above-crossing tunnelling at the tunnel location is calculated through Mindlin's solution. Second, the deformation response of the beam subjected to an unloading stress is calculated by the finite difference method. Two engineering cases are used to verify the research. The results indicate that the proposed model is more accurate than traditional models in predicting the maximum uplift value, which is basically consistent with the observations. Due to the existence of segment staggering, the longitudinal influence range of the calculation by two models is larger than the actual measurement.

A mutation in ß-amyloid precursor protein renders SH­SY5Y cells vulnerable to isoflurane toxicity: The role of inositol 1,4,5­trisphosphate receptors.

Isoflurane is a commonly used inhaled anesthetic, which induces apoptosis of SH­SY5Y cells in a dose­ and time­dependent manner; however, the underlying mechanisms remain unknown. The authors of the present study hypothesized that a mutation in ß­amyloid precursor protein (APP), which is a gene associated with familial Alzheimer's disease, may render cells vulnerable to isoflurane­induced cytotoxicity via activation of inositol 1,4,5­trisphosphate receptors (IP3R). In the present study, SH­SY5Y cells were transfected with a vector or with mutated APP, and were treated with the equivalent of 1 minimum alveolar concentration (MAC) isoflurane for 8 h. Cell apoptosis rate, alterations to cytosolic calcium concentrations ([Ca2+]c), and protein levels of IP3R were determined following exposure of cells to isoflurane. In addition, the effects of the IP3R antagonist xestospongin C were determined on isoflurane­induced cytotoxicity and calcium release from the endoplasmic reticulum (ER) of mutated APP­ and vector­transfected SH­SY5Y cells. Treatment with isoflurane (1 MAC) for 8 h induced a higher degree of cytotoxicity, and a marked increase in [Ca2+]c and IP3R protein levels in mutated APP­transfected SH­SY5Y cells compared with vector­transfected SH­SY5Y cells. Xestospongin C significantly attenuated isoflurane­mediated cytotoxicity and inhibited calcium release from the ER of SH­SY5Y cells. These results indicated that the APP mutation may render SH­SY5Y cells vulnerable to isoflurane neurotoxicity, and the underlying mechanism may be associated with Ca2+ dysregulation via overactivation of IP3R.

Effects of calpain on sevoflurane-induced aged rats hippocampal neuronal apoptosis.

BACKGROUND: Sevoflurane is one of the most commonly used volatile anesthetics and it has been shown to induce widespread apoptotic neurodegeneration in aged rat. Calpain is also activated during apoptosis in several types of cells. We hypothesized that calpain resulted in apoptosis under long time sevoflurane exposure, and it might play a role in the sevoflurane-induced memory impairment in aged rats. METHODS: Seventy-two 18-month-old male Sprague-Dawley rats were randomly divided into three groups (n = 24): Control group rats were exposed to simply humid 50 % O2 balanced by N2 for 3 h; While M group rats received calpain inhibitor 10 mg/kg via the tail vein intravenously at 30 min before the animals inhaled 3 % sevoflurane for 3 h, subsequently received MDL 28170 3.33 mg/kg/h for 3 h. Sev group rats were only exposed to 3 % sevoflurane for 3 h without calpain inhibitor. Morris Water Maze was used to test the ability of learning and memory. Cytosolic calcium concentration was measured by using flow cytometry. Annexin-V labeled with a fluorophore or biotin can identify apoptotic cells by binding to PS. The expression of calpain in the hippocampus of rats was tested by Western blots. RESULTS: The results showed that the M group had a shorter latency and had a larger number of times crossing over the previous platform site than that of the Sev group. Compared with Sev group, apoptosis rate and 76/80 kDa ratio of µ-calpain were significantly decreased in M group on the 1st day. CONCLUSIONS: Sevoflurane might induce apoptosis through increasing [Ca(2+)]c and the activity of µ-calpain, which might be identified at least partially the molecular mechanism by which sevoflurane induces apoptosis.