Fault zone heterogeneities explain depth-dependent pattern and evolution of slow earthquakes in Cascadia.

Slow earthquakes including tremor and slow-slip events are recent additions to the conventional earthquake family and have a close link to megathrust earthquakes. Slow earthquakes along the Cascadia subduction zone display a diverse behavior at different spatiotemporal scales and an intriguing increase of events frequency with depth. However, what causes such variability, especially the depth-dependent behavior is not well understood. Here we build on a heterogeneous asperities-in-matrix fault model that incorporates differential pore pressure in a rate-and-state friction framework to investigate the underlying processes of the observed episodic tremor and slow-slip (ETS) variability. We find that the variations of effective normal stress (pore pressure) is one important factor in controlling ETS behavior. Our model reproduces the full complexity of ETS patterns and the depth-frequency scaling that agree quantitatively well with observations, suggesting that fault zone heterogeneities can be one viable mechanism to explain a broad spectrum of transient fault behaviors.

Evaluation of adsorption selectivity of immunoglobulins M, A and G and purification of immunoglobulin M with mixed-mode resins.

This study investigated adsorption selectivity of immunoglobulin M (IgM), immunoglobulin A (IgA) and immunoglobulin (IgG) on four mixed-mode resins with the functional ligands of 4-mercatoethyl-pyridine (MEP), 2-mercapto-1-methylimidazole (MMI), 5-aminobenzimidazole (ABI) and tryptophan-5-aminobenzimidazole (W-ABI), respectively. IgM purification processes with mixed-mode resins were also proposed. All resins showed typical pH-dependent adsorption, and high adsorption capacity was found at pH 5.0-8.0 with low adsorption capacity under acidic conditions. Meanwhile, high selectivity of IgM/IgA and IgM/IgG was obtained with ABI-4FF and MMI-4FF resins at pH 4.0-5.0, which was used to develop a method for IgM, IgA and IgG separation by controlling loading and elution pH. Capture of monoclonal IgM from cell culture supernatant with ABI-4FF resins was studied and high purity (∼99%) and good recovery (80.8%) were obtained. Moreover, IgM direct separation from human serum with combined two-step chromatography (ABI-4FF and MMI-4FF) was investigated, and IgM purity of 65.2% and a purification factor of 28.3 were obtained after optimization. The antibody activity of IgM was maintained after purification. The results demonstrated that mixed-mode chromatography with specially-designed ligands is a promising way to improve adsorption selectivity and process efficiency of IgM purification from complex feedstock.

Selectivity evaluation and separation of human immunoglobulin G, Fab and Fc fragments with mixed-mode resins.

Adsorption selectivity is critical important for mixed-mode chromatography with specially-designed ligands. Human immunoglobulin G (hIgG), Fc and Fab fragments were used in the present work to evaluate adsorption behavior and binding selectivity of four mixed-mode resins with the ligands of 4-mercatoethyl-pyridine (MEP), 2-mercapto-1-methylimidazole (MMI), 5-aminobenzimidazole (ABI) and tryptophan-5-aminobenzimidazole (W-ABI), respectively. The resins showed an obvious pH-dependent adsorption behavior. High adsorption capacities were found at neutral pH for hIgG, Fc and Fab, and almost no adsorption happened under acidic conditions. An adsorption selectivity index was proposed to evaluate separation efficiency. High specificity of hIgG/Fc was found at pH 8.9 for MEP resin, and for W-ABI resin at pH 8.0 and 8.9. In addition, isothermal titration calorimetry was used to evaluate ligand-protein interactions. Finally, the separation of hIgG and Fc (1:1) was optimized with mixed-mode resins, and the best separation performance was obtained with W-ABI-based resin. Loading at pH 8.0 resulted in the flow through of Fc with purity of 90.4% and recovery of 98.8%, while elution at pH 3.6 provided hIgG with purity of 99.7% and recovery of 86.5%.

Sucrose fed-batch strategy enhanced biomass, polysaccharide, and ganoderic acids production in fermentation of Ganoderma lucidum 5.26.

Ganoderma, as a Chinese traditional medicine, has multiple bioactivities. However, industrial production was limited due to low yield during Ganoderma fermentation. In this work, sucrose was found to greatly enhance intracellular polysaccharide (IPS) content and specific extracellular polysaccharide (EPS) production rate. The mechanism was studied by analyzing the activities of enzymes related to polysaccharide biosynthesis. The results revealed that sucrose regulated the activities of phosphoglucomutase and phosphoglucose isomerase. When glucose and sucrose mixture was used as carbon source, biomass, polysaccharide and ganoderic acids (GAs) production was greatly enhanced. A sucrose fed-batch strategy was developed in 10-L bioreactor, and was scaled up to 300-L bioreactor. The biomass, EPS and IPS production was 25.5, 2.9 and 4.8 g/L, respectively, which was the highest biomass and IPS production in pilot scale. This study provides information for further understanding the regulation mechanism of Ganoderma polysaccharide biosynthesis. It demonstrates that sucrose fed-batch is a useful strategy for enhancing Ganoderma biomass, polysaccharide and GAs production.

2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone inhibits apoptosis of MIN6 cells via improving mitochondrial function.

Mitochondrial dysfunction due to oxidative stress and concomitant beta-cell apoptosis may play a key role in type 2 diabetes. Inhibiting beta-cell apoptosis through ameliorating oxidative mitochondrial dysfunction with specific natural products may have preventive or therapeutic potential. In this study, the anti-apoptotic effect of 2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone (DMC), a isolated chalcone from the buds of Cleistocalyx operculatus, on H2O2 induced MIN6 cells damage was investigated. Exposure to H2O2 at 250 microM for 3 h, the viability of MIN6 cells was significantly decreased and the apoptosis apparently occurred. A pre-treatment with DMC at the concentrations of 12.5-25 microM, before H2O2 addition, reduced nucleus fragmentation, decreased endogenous reactive oxygen species (ROS) production, and improved mitochondrial potential (MMP), and consequently, inhibited apoptosis. Furthermore, decreased activities of caspase-3 and caspase-9 were observed. These results clearly demonstrated DMC protected MIN6 cells against apoptosis due to its highly protective effect on mitochondria, and thus, it has great potential as a candidate drug for the diabetes care.

In vitro investigation of 2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone for glycemic control.

2',4'-Dihydroxy-6'-methoxy-3',5'-dimethylchalcone (DMC), a compound isolated and purified from the dried flower buds of Cleistocalyx operculatus (Roxb.) Merr. et Perry (Myrtaceae), was investigated for its glucose control benefits using in vitro methods. DMC showed strong noncompetitive (IC(50) of 43 µM) inhibition of pancreatic α-amylase; it was, however, ineffective against intestinal α-glucosidase. In addition, DMC exhibited remarkable glucose transport inhibition effects in both simulated fasting and fed states in Caco-2 cell monolayers (P < 0.05). Besides, exposure of MIN6 cells to 250 µM H(2)O(2) for 1 h caused a significant viability loss and insulin secretion reduction. Pretreatment of MIN6 cells with DMC for 2 h protected against the H(2)O(2)-induced decrease in glucose-stimulated insulin secretion in a dose-dependent manner and also enhanced the impaired basal insulin secretion. Such effects highlight the therapeutic potential of DMC in the management of hyperglycemia.