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At the time of completion in 1961, the roof of St. Charles Church became the largest unbalanced hyperbolic paraboloid structure in the United States and the only shell structure in Spokane, WA. Situated on an 8-acre site on the north side of the city, St. Charles is a modernist structure designed through partnership of Funk, Molander & Johnson engineers, architect William C. James and in consultation with Professor T.Y. Lin of the Structural Engineering Laboratory at the University of California, Berkeley. This asymmetric structure spans over 33.5 m (110 ft) and utilizes folded edge beams that taper from 1067 mm (42 in) at the base to a 76.2 mm (3 in) thickness at the topmost edge using regular strength reinforcing steel and concrete load carrying components. The novelty of the pre-stressed shell structure serves both architectural and structural design criteria by delivering a large, uninterrupted interior sanctuary space in materially and economically efficient manner. This structural assessment summarizes the roof’s historic design and construction according to the original construction documents, newspaper reports and historic photographs. The FEA is completed using UBC 1955 design loads and ACI 334 Concrete Shell Structures provisions.

Metabolic dysfunction-associated steatohepatitis (MASH) represents a global health threat. MASH pathophysiology involves hepatic lipid accumulation and progression to severe conditions like cirrhosis and, eventually, hepatocellular carcinoma. Fibroblast growth factor (FGF)-19 has emerged as a key regulator of metabolism, offering potential therapeutic avenues for MASH and associated disorders. We evaluated the therapeutic potential of non-mitogenic (NM)-FGF19 mRNA formulated in liver-targeted lipid nanoparticles (NM-FGF19-mRNAs-LNPs) in C57BL/6NTac male mice with diet-induced obesity and MASH (DIO-MASH: 40% kcal fat, 20% kcal fructose, 2% cholesterol). After feeding this diet for 21 weeks, NM-FGF19-mRNAs-LNPs or control (C-mRNA-LNPs) were administered (0.5 mg/kg, i.v.) weekly for another six weeks, in which diet feeding continued. NM-FGF19-mRNAs-LNPs treatment in DIO-MASH mice resulted in reduced body weight, adipose tissue depots, and serum transaminases, along with improved insulin sensitivity. Histological analyses confirmed the reversal of MASH features, including steatosis reduction without worsening fibrosis. NM-FGF19-mRNAs-LNPs reduced total hepatic bile acids (BAs) and changed liver BA composition, markedly influencing cholesterol homeostasis and metabolic pathways as observed in transcriptomic analyses. Extrahepatic effects included the down-regulation of metabolic dysfunction-associated genes in adipose tissue. This study highlights the potential of NM-FGF19-mRNA-LNPs therapy for MASH, addressing both hepatic and systemic metabolic dysregulation. NM-FGF19-mRNA demonstrates efficacy in reducing liver steatosis, improving metabolic parameters, and modulating BA levels and composition. Given the central role played by BA in dietary fat absorption, this effect of NM-FGF19-mRNA may be mechanistically relevant. Our study underscores the high translational potential of mRNA-based therapies in addressing the multifaceted landscape of MASH and associated metabolic perturbations. [ABSTRACT FROM AUTHOR]

This research compared two common glass design methods through a set of original worked examples on two-edge supported spans. A comparison of the results revealed the importance of accurately modeling actual material behavior to: (1) optimize materially efficient designs; and (2) produce designs with consistently reliable levels of risk. Results showed that minimization of material usage correlates to a consistent probability of failure metrics. For the two-edge supported spans (i.e., simply supported beam), the average monolithic plate thickness found using allowable stress design methods was 16.4% greater than that calculated using strictly probabilistic-based design. [ABSTRACT FROM AUTHOR]