Design Optimisation Analysis of Isolating Wall for Separated Widening Embankment on Soft Ground

In this paper, the typical cases of subgrade separated widening project in China are summarised. The research progress of subgrade separated widening and isolating wall applications are reviewed in highway reconstruction and extension. A numerical model is established based on the PLAXIS finite element software, considering both material nonlinearity and geometric nonlinearity. The effect mechanism of the isolating wall is discussed on the settlement control of the new and existing embankment on soft ground. The effect rule of the core design parameters of the isolating wall is revealed on the settlement disturbance of the existing embankment, such as location, depth, thickness and elastic modulus, and the weight rank of the influence is analysed. The results indicate that the isolating wall effectively reduces the lateral displacement and vertical settlement of the existing embankment, and there is an optimal design location for the isolating wall. In addition, with the increase of design parameters of the isolating wall, including depth, thickness and elastic modulus, the overall settlement of the existing embankment tends to be uniform, and there are optimal values. Furthermore, the depth of isolating wall is given priority, compared to location, thickness and elastic modulus during the isolating wall design process. The research results lay a theoretical foundation for the design optimisation of the isolating wall in the separated widening project of soft ground

Analysis of Settlement Behaviour of Soft Ground Under Wide Embankment

An elastoplastic numerical model for calculating the consolidation settlement of wide embankment on soft ground is established using PLAXIS finite element software to investigate the settlement behaviour of soft ground under the wide embankment. The distribution rules are analysed and compared to narrow embankments, such as surface settlements of ground and embankment, lateral displacement of soft ground at the foot of embankment slope and excess pore pressure in soft ground. The influence rule of elastic modulus of soft ground on the settlement of soft ground under wide embankment is discussed. The results show that the settlement distributions of wide and narrow embankments on soft ground are “W” and “V” shapes, respectively. The maximum settlement of wide embankment is near the foot of the embankment slope, which is unequal to the settlement at the centreline of the embankment. The lateral displacement distribution rules of soft ground are both “belly” shaped at the foot of two types of embankments slope. However, the lateral displacement of the wide embankment is larger in each corresponding stage. During the construction period, the excess pore pressure in the soft ground under the wide embankment is much higher than that of the narrow embankment, so the post-construction consolidation time of the wide embankment is longer. Moreover, the macroscopic settlement rule of the wide embankment is still the same with the increase of elastic modulus of soft ground

The Fas/Fas ligand death receptor pathway contributes to phenylalanine-induced apoptosis in cortical neurons.

Phenylketonuria (PKU), an autosomal recessive disorder of amino acid metabolism caused by mutations in the phenylalanine hydroxylase (PAH) gene, leads to childhood mental retardation by exposing neurons to cytotoxic levels of phenylalanine (Phe). A recent study showed that the mitochondria-mediated (intrinsic) apoptotic pathway is involved in Phe-induced apoptosis in cultured cortical neurons, but it is not known if the death receptor (extrinsic) apoptotic pathway and endoplasmic reticulum (ER) stress-associated apoptosis also contribute to neurodegeneration in PKU. To answer this question, we used specific inhibitors to block each apoptotic pathway in cortical neurons under neurotoxic levels of Phe. The caspase-8 inhibitor Z-IETD-FMK strongly attenuated apoptosis in Phe-treated neurons (0.9 mM, 18 h), suggesting involvement of the Fas receptor (FasR)-mediated cell death receptor pathway in Phe toxicity. In addition, Phe significantly increased cell surface Fas expression and formation of the Fas/FasL complex. Blocking Fas/FasL signaling using an anti-Fas antibody markedly inhibited apoptosis caused by Phe. In contrast, blocking the ER stress-induced cell death pathway with salubrinal had no effect on apoptosis in Phe-treated cortical neurons. These experiments demonstrate that the Fas death receptor pathway contributes to Phe-induced apoptosis and suggest that inhibition of the death receptor pathway may be a novel target for neuroprotection in PKU patients

Novel mutations in the SCNN1A gene causing Pseudohypoaldosteronism type 1.

Pseudohypoaldosteronism type 1 (PHA1) is a rare inherited disease characterized by resistance to the actions of aldosterone. Mutations in the subunit genes (SCNN1A, SCNN1B, SCNN1G) of the epithelial sodium channel (ENaC) and the NR3C2 gene encoding the mineralocorticoid receptor, result in systemic PHA1 and renal PHA1 respectively. Common clinical manifestations of PHA1 include salt wasting, hyperkalaemia, metabolic acidosis and elevated plasma aldosterone levels in the neonatal period. In this study, we describe the clinical and biochemical manifestations in two Chinese patients with systemic PHA1. Sequence analysis of the SCNN1A gene revealed a compound heterozygous mutation (c.1311delG and c.1439+1G>C) in one patient and a homozygous mutation (c.814_815insG) in another patient, all three variants are novel. Further analysis of the splicing pattern in a minigene construct showed that the c.1439+1G>C mutation can lead to the retainment of intron 9 as the 5'-donor splice site disappears during post-transcriptional processing of mRNA. In conclusion, our study identified three novel SCNN1A gene mutations in two Chinese patients with systemic PHA1

In Vivo and In Vitro Study on the Efficacy of Terpinen-4-ol in Dextran Sulfate Sodium-Induced Mice Experimental Colitis

The purpose of this study was to investigate the protective effects of Terpinen-4-ol (TER) on dextran sulfate sodium (DSS)-induced experimental colitis and clarify the possible mechanisms. In vivo, an acute colitis model was used to confirm the anti-inflammatory activity and the possible mechanisms of TER in C57BL/6 and NLRP3−/− mice. In vitro, we performed further study, using RAW264.7 cells and Caco-2 cells, to confirm the molecular mechanisms of TER on inflammatory response. In C57BL/6 mice, TER alleviated DSS-induced disease activity index (DAI), colon length shortening, colonic pathological damage, and myeloperoxidase (MPO) activities. The production of pro-inflammatory mediators was significantly decreased by TER. Furthermore, TER inhibited NF-κB and NLRP3 inflammasome activation. Surprisingly, TER reduced the plasmatic lipopolysaccharide (LPS) concentration and re-balanced Escherichia coli (E. coli) and Lactobacillus levels. In addition, TER prevented the impairment of colon epithelium barrier by regulating the expression of zonula occludens-1 and occludin. In vitro, the results showed that TER significantly suppressed NLRP3 inflammasome activation in LPS-stimulated RAW264.7 cells, as indicated by decreased expression of NLRP3 and caspase-1, and lowered interleukin-1β secretion. In contrast, mice deficient for NLRP3 were less sensitive to DSS-induced acute colitis, and TER treatment exerted little protective effect on DSS-induced intestinal inflammation in NLRP3−/− mice. The protective effect of TER may be largely attributed to its inhibition of NLRP3 inflammasome activation in colon. Taken together, our findings showed that TER might be a potential agent for the treatment of ulcerative colitis