Application of Conditional Mean Spectrum in Nonlinear Response History Analysis of Tall Buildings on Soft Soil

The uniform hazard spectrum (UHS) and conditional mean spectrum (CMS) are commonly used as target spectra in selecting and scaling of records to be used in nonlinear response history analysis (NLRHA). When using CMS with tall buildings, CMS ground motions conditioned at multiple natural periods of the buildings should be considered. The application of CMS ground motions in NLRHA to estimate seismic demands for design of tall buildings located on soft-soil layers in Bangkok is investigated in this study. The seismic demands computed using multiple sets of CMS ground motions are compared with those computed using a single set of UHS spectral matching ground motions. Four existing tall buildings subjected to earthquake excitations in Bangkok were considered. The NLRHA was conducted using multiple sets of CMS ground motions, where periods of interest  were considered at the periods closest to the periods of the first-three translational modes of the building in the direction of excitation. It was found that CMS ground motions conditioned at the higher-mode periods result in larger force demands than CMS ground motions conditioned at the fundamental period for some locations along the height of the building. The envelope of demands obtained by using multiple sets of CMS ground motions conditioned at different periods should be used in design but requires significant computational effort. Using UHS spectral matching ground motions can provide results close to such an envelope and reduce the computational effort significantly

Modeling of Precast Concrete Load-Bearing Walls Exposed to Fire

The performance of precast concrete load-bearing walls exposed to fire is investigated using 3-D thermal and structural models. The thermal model is validated by comparing the predicted temperatures with results from the fire tests carried out in the present study, previous experimental studies, and Eurocode 2. The structural model is validated by comparing the predicted displacements and crack patterns with results from the fire tests carried out in the present study. It is found that the results obtained from the thermal model and the structural model are in line with the experimental data and Eurocode 2 results. The validated 3-D model of precast concrete load-bearing walls is used to study the effect of load level, slenderness ratio and boundary conditions on the fire performance of the walls. The results show that the fire resistance rating of load-bearing walls decreases with increasing load level and slenderness ratio, while the fire resistance rating of the walls increases when rotational restraints are imposed at the ends of the walls. Finally, equations are presented for estimating the fire resistance rating of the walls with different support conditions

Molecular basis for the folding of β-helical autotransporter passenger domains

Bacterial autotransporters comprise a C-terminal β-barrel domain, which must be correctly folded and inserted into the outer membrane to facilitate translocation of the N-terminal passenger domain to the cell exterior. Once at the surface, the passenger domains of most autotransporters are folded into an elongated β-helix. In a cellular context, key molecules catalyze the assembly of the autotransporter β-barrel domain. However, how the passenger domain folds into its functional form is poorly understood. Here we use mutational analysis on the autotransporter Pet to show that the β-hairpin structure of the fifth extracellular loop of the β-barrel domain has a crucial role for passenger domain folding into a β-helix. Bioinformatics and structural analyses, and mutagenesis of a homologous autotransporter, suggest that this function is conserved among autotransporter proteins with β-helical passenger domains. We propose that the autotransporter β-barrel domain is a folding vector that nucleates folding of the passenger domain

Assembly of the type II secretion system such as found in Vibrio cholerae depends on the novel Pilotin AspS

The Type II Secretion System (T2SS) is a molecular machine that drives the secretion of fully-folded protein substrates across the bacterial outer membrane. A key element in the machinery is the secretin: an integral, multimeric outer membrane protein that forms the secretion pore. We show that three distinct forms of T2SSs can be distinguished based on the sequence characteristics of their secretin pores. Detailed comparative analysis of two of these, the Klebsiella-type and Vibrio-type, showed them to be further distinguished by the pilotin that mediates their transport and assembly into the outer membrane. We have determined the crystal structure of the novel pilotin AspS from Vibrio cholerae, demonstrating convergent evolution wherein AspS is functionally equivalent and yet structurally unrelated to the pilotins found in Klebsiella and other bacteria. AspS binds to a specific targeting sequence in the Vibrio-type secretins, enhances the kinetics of secretin assembly, and homologs of AspS are found in all species of Vibrio as well those few strains of Escherichia and Shigella that have acquired a Vibrio-type T2SS

A molecular basis for the association of the HLA-DRB1 locus, citrullination, and rheumatoid arthritis

Rheumatoid arthritis (RA) is strongly associated with the human leukocyte antigen (HLA)- DRB1 locus that possesses the shared susceptibility epitope (SE) and the citrullination of self-antigens. We show how citrullinated aggrecan and vimentin epitopes bind to HLADRB1* 04:01/04. Citrulline was accommodated within the electropositive P4 pocket of HLA-DRB1*04:01/04, whereas the electronegative P4 pocket of the RA-resistant HLADRB1* 04:02 allomorph interacted with arginine or citrulline-containing epitopes. Peptide elution studies revealed P4 arginine-containing peptides from HLA-DRB1*04:02, but not from HLA-DRB1*04:01/04. Citrullination altered protease susceptibility of vimentin, thereby generating self-epitopes that are presented to T cells in HLA-DRB1*04:01+ individuals. Using HLA-II tetramers, we observed citrullinated vimentin- and aggrecan-specific CD4+ T cells in the peripheral blood of HLA-DRB1*04:01+ RA-affected and healthy individuals. In RA patients, autoreactive T cell numbers correlated with disease activity and were deficient in regulatory T cells relative to healthy individuals. These findings reshape our understanding of the association between citrullination, the HLA-DRB1 locus, and T cell autoreactivity in RA