Instability And Collapse Behavior Of A Seismic Structure

The collapse behavior of a 22-story steel building during the September 19, 1985, Mexico earthquake is investigated by studying hysteretic behavior, ductility factors of individual structural components, and overall instability of the building. The hysteresis models for truss-type girders, bracing members, and box columns to be used in the inelastic analysis of this building are developed. A series of inelastic analyses have been performed for the building by using the multicomponent seismic input of actual Mexico City earthquake records. It was found that the structural response exceeds the original design ductility of this building because most girders in the building have suffered large ductility\u27s. Due to the load redistribution effects from the ductile-failed girders, local buckling developed at many columns on floors 2, 3, and 4. Therefore, most columns on floors 2 through 4 lost their load carrying capacities and rigidities which then caused the building to tilt and rotate. As a result, more columns on floors 5 through 7 developed local buckling and more bracing members buckled. It is believed that ductile failures of girders combined with the local buckling of columns in the lower part of the building resulted in significant story drift, building tilt, P-A effect, and the failure mechanism

Cellular Mechanisms of Etrolizumab Treatment in Inflammatory Bowel Disease

Background: Anti-integrin therapy is a new frontline strategy in the treatment of inflammatory bowel diseases (IBD). The anti-β7 integrin antibody etrolizumab is currently being investigated for safety and efficacy in Crohn’s disease (CD) and ulcerative colitis (UC) in several phase III trials. Mechanistically, etrolizumab is known to block β7 integrin ligand binding and reduces intestinal trafficking of β7-expressing cells. Etrolizumab blocks β7 integrin ligand binding and reduces β7-positive lymphocyte migration and retention in the inflamed gut mucosa, but the exact mechanisms by which this inhibition occurs are not fully understood.Methods: Cellular effects of etrolizumab or etrolizumab surrogate antibody (etrolizumab-s) were investigated in cell culture models and analyzed by flow cytometry, fluorescence microscopy, ImageStream®, stimulated emission depletion (STED) microscopy and functional dynamic in vitro adhesion assays. Moreover, effects on α4β7 integrin were compared with the pharmacodynamically similar antibody vedolizumab.Results: As demonstrated by several different approaches, etrolizumab and etrolizumab-s treatment led to internalization of β7 integrin. This resulted in impaired dynamic adhesion to MAdCAM-1. Internalized β7 integrin localized in endosomes and re-expression of β7 was dependent on de novo protein synthesis. In vitro etrolizumab treatment did not lead to cellular activation or cytokine secretion and did not induce cytotoxicity. Internalization of α4β7 integrin was increased with etrolizumab compared with vedolizumab.Discussion: Our data suggest that etrolizumab does not elicit secondary effector functions on the single cell level. Integrin internalization may be an important mechanism of action of etrolizumab, which might explain some but not all immunological effects observed with etrolizumab

High Affinity Antigen Recognition of the Dual Specific Variants of Herceptin Is Entropy-Driven in Spite of Structural Plasticity

The antigen-binding site of Herceptin, an anti-human Epidermal Growth Factor Receptor 2 (HER2) antibody, was engineered to add a second specificity toward Vascular Endothelial Growth Factor (VEGF) to create a high affinity two-in-one antibody bH1. Crystal structures of bH1 in complex with either antigen showed that, in comparison to Herceptin, this antibody exhibited greater conformational variability, also called “structural plasticity”. Here, we analyzed the biophysical and thermodynamic properties of the dual specific variants of Herceptin to understand how a single antibody binds two unrelated protein antigens. We showed that while bH1 and the affinity-improved bH1-44, in particular, maintained many properties of Herceptin including binding affinity, kinetics and the use of residues for antigen recognition, they differed in the binding thermodynamics. The interactions of bH1 and its variants with both antigens were characterized by large favorable entropy changes whereas the Herceptin/HER2 interaction involved a large favorable enthalpy change. By dissecting the total entropy change and the energy barrier for dual interaction, we determined that the significant structural plasticity of the bH1 antibodies demanded by the dual specificity did not translate into the expected increase of entropic penalty relative to Herceptin. Clearly, dual antigen recognition of the Herceptin variants involves divergent antibody conformations of nearly equivalent energetic states. Hence, increasing the structural plasticity of an antigen-binding site without increasing the entropic cost may play a role for antibodies to evolve multi-specificity. Our report represents the first comprehensive biophysical analysis of a high affinity dual specific antibody binding two unrelated protein antigens, furthering our understanding of the thermodynamics that drive the vast antigen recognition capacity of the antibody repertoire

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Analytical approaches for designing a class of material flow systems

Ph.D.Gunter P. Shar

DEA malmquist productivity measure: Taiwanese semiconductor companies,”

Abstract In this research we employ data envelopment analysis (DEA) to measure the Malmquist productivity of semiconductor packaging and testing firms in Taiwan from 2000 to 2003. Malmquist productivity has three components: the measurement of technical change, the measurement of the frontier forward shift, and the measurement of the frontier backward shift of a company over two consecutive periods. This approach not only reveals patterns of productivity change and presents a new interpretation along with the managerial implication of each Malmquist component, but also identifies the strategy shifts of individual companies based upon isoquant changes. Therefore, one can judge with greater accuracy whether or not such strategy shifts are favorable and promising. We use slacks-based measurement (SBM) and Super-SBM models to obtain more accurate measurements. Comparison is made between the results from SBM/Super-SBM and CCR models.

Procedure to Solve Network DEA Based on a Virtual Gap Measurement Model

Network DEA models assess production systems that contain a set of network-structured subsystems. Each subsystem has input and output measures from and to the external network and has intermediate measures that link to other subsystems. Most published studies demonstrate how to employ DEA models to establish network DEA models. Neither static nor dynamic network DEA models adjust the links. This paper applies the virtual gap measurement (VGM) model to construct a mixed integer program to solve dynamic network DEA problems. The mixed integer program sets the total numbers of “as-input” and “as-output” equal to the total number of links in the objective function. To obtain the best-practice efficiency, each DMU determines a set of weights for inputs, outputs, and links. The links are played either “as-input” or “as-output.” Input and as-input measures reduce slack, whereas output and as-output measures increase slacks to attain their target on the production frontier