Geosynthetic reinforced soil (GRS) bridge abutments are becoming widely used in transportation infrastructure and provide many advantages over traditional pile-supported designs, including lower ...cost, faster and easier construction, and smoother transition between the bridge and approach roadway. Seismic events represent a severe loading condition and experimental testing and evaluation are needed to understand the potential issues and performance characteristics. This study involves a comprehensive evaluation of the performance of GRS bridge abutments for the service limit state, the strength limit state, and an extreme event limit state (i.e., seismic loading conditions) using both numerical simulations and physical modeling experiments. A numerical model was developed for GRS bridge abutments under service loading conditions and was validated using field measurements. Simulation results indicate that the horizontal restraining forces generated from the bridge structure can have an important effect on reducing lateral facing displacements and bridge seat settlements of GRS bridge abutments. Parametric studies were conducted to investigate the effects of various design parameters on the performance of GRS bridge abutments for service loading conditions, and the results indicate that reinforcement spacing, reinforcement stiffness, bridge load, and abutment height have the most significant effects on the lateral facing displacements and bridge seat settlements. The numerical model was enhanced by incorporating the strain softening behavior for backfill soil and the rate-dependent behavior for geosynthetic reinforcement to simulate the load-deformation behavior of GRS bridge abutments up to failure condition. A linearly elastic reinforcement model can capture the deformation behavior of GRS bridge abutments for service loads, but not for larger applied loads approaching failure. The geometry parameters for GRS bridge abutments have important effects on the internal failure surface of the GRS bridge abutments, and the internal failure surface manifests as a bilinear surface that starts at the heel of the bridge footing, moves vertically downward to mid-height of the GRS bridge abutment, and then linearly to the toe of the GRS bridge abutment. The seismic response of GRS bridge abutments was evaluated using an experimental testing program. Shaking table tests were conducted on six half-scale GRS bridge abutments by application of a series of shaking events in the directions longitudinal and transverse to the bridge beam. Experimental design of the model specimen followed established similitude relationships for shaking table testing of reduced-scale models in a 1g gravitational field, including scaling of model geometry, geosynthetic reinforcement stiffness, backfill soil modulus, bridge load, and characteristics of the earthquake motions. Experimental results indicate that the seismic facing displacements and bridge seat settlements for GRS bridge abutments are small and will likely not have a major effect on the bridge performance. Reinforcement spacing and stiffness have the most important effects on the seismic performance of GRS bridge abutments.
Reduced cellular immune function in patients after liver transplantation easily results in many types of viral infections, such as Epstein-Barr virus. Epstein-Barr virus is a Γ-herpesvirus and is ...related to many malignant diseases, especially epithelial and lymph tumors. The abnormal interaction of cluster of differentiation 40 with cluster of differentiation 40 ligand and expression of cluster of differentiation 40 ligand are considered closely related to the development of myeloma cells. This study explored the influence and mechanism of Epstein-Barr virus infection on the phenotype and biological behavior of myeloma cells after liver transplantation. Flow cytometry was used to detect coexpression of cluster of differentiation 40 and cluster of differentiation 40 ligand in 10 samples of freshly isolated multiple myeloma cells. Cluster of differentiation 40 and cluster of differentiation 40 ligand were coexpressed in sample Nos. 5, 8, 9, and 10, particularly in sample No. 5. Western blot analysis was used to detect the expression of the Epstein-Barr virus antigens latent membrane protein 1 and Epstein-Barr virus nuclear antigen 2 in the multiple myeloma cell line RPMI 8226 infected with Epstein-Barr virus. The antigen expression indicated that Epstein-Barr virus can infect multiple myeloma virus cells
in vitro
. Reverse transcription-polymerase chain reaction revealed upregulated expression of cluster of differentiation 40 ligand on the infected RPMI 8226 cells, which may be involved in the anti-apoptosis activity of the infected cells. Confocal microscopy showed that pairs of molecules of cluster of differentiation 40, cluster of differentiation 40 ligand, and latent membrane protein 1 were colocalized on the surface of the infected cells. CXC chemokine receptor 4 was upregulated on the RPMI 8226 cells after Epstein-Barr virus infection. The migratory ability of the infected cells improved in the presence of the chemokine stromal cell-derived factor-1α. Anti-apoptosis and migration are known important biological characteristics of malignant cells. Our results indicate the involvement of Epstein-Barr virus in the origin and development of multiple myeloma. The risk of multiple myeloma increases when Epstein-Barr virus infects B cells in the germinal center, which may result in an anti-apoptosis effect of B cells and an improved ability to migrate from the germinal center to peripheral blood.
Stem cells need to be protected from genotoxic and proteotoxic stress to maintain a healthy pool throughout life
. Little is known about the proteostasis mechanism that safeguards stem cells. Here we ...report endoplasmic reticulum-associated degradation (ERAD) as a protein quality checkpoint that controls the haematopoietic stem cell (HSC)-niche interaction and determines the fate of HSCs. The SEL1L-HRD1 complex, the most conserved branch of ERAD
, is highly expressed in HSCs. Deletion of Sel1l led to niche displacement of HSCs and a complete loss of HSC identity, and allowed highly efficient donor-HSC engraftment without irradiation. Mechanistic studies identified MPL, the master regulator of HSC identity
, as a bona fide ERAD substrate that became aggregated in the endoplasmic reticulum following ERAD deficiency. Restoration of MPL signalling with an agonist partially rescued the number and reconstitution capacity of Sel1l-deficient HSCs. Our study defines ERAD as an essential proteostasis mechanism to safeguard a healthy stem cell pool by regulating the stem cell-niche interaction.
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