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This study proposes a surrogate-based cyber-physical aerodynamic shape optimization (SB-CP-ASO) approach for high-rise buildings under wind loading. Three components are developed in the SB-CP-ASO procedure: (1) an adaptive subtractive manufacturing technique, (2) a high-throughput wind tunnel testing procedure, and (3) a flexible infilling strategy. The downtime of the procedure is minimized through a parallel manufacturing and testing (llM&T) technique. An unexplored double-section setback strategy with various cross-sections and transitions positions is used to demonstrate the performance of the proposed procedure. A total of 173 physical specimens were evaluated to reach the optimization convergence within the reserved testing window. Further analysis of promising shapes considering multiple design wind speeds is suggested to achieve target performance objectives at various hazard levels. Practical information on setback and cross-section modification strategies is discussed based on the optimization results. In comparison with a square benchmark model, the roof drifts for promising candidates with similar building volumes are reduced by more than 70% at wind speeds higher than 50 m/s. This procedure is expected to provide an efficient platform between owners, architects, and structural engineers to identify ideal candidates within a defined design space for real-world applications of high-rise buildings. 

This study explores the complementary effects of side and corner modification on the aerodynamic behavior for high-rise buildings across representative design wind speeds. Twelve doubly-symmetric prismatic models were examined using high-frequency force balance (HFFB) wind tunnel testing at the University of Florida. The effectiveness of the aerodynamic strategies was quantified using roof drift and roof acceleration under different design wind speeds covering serviceability and survivability. The results show that both corner and side modifications can achieve promising aerodynamic performance under high design wind speeds. However, the effectiveness of the aerodynamic strategies is significantly reduced under low design wind speeds. With a corner modification strategy, the vortex shedding frequency is increased, leading to worse across-wind response at lower design wind speeds when compared to the square benchmark model. To address this issue, side modifications (i.e., side protrusions) can be used to preserve the vortex shedding frequency and achieve competitive aerodynamic performance while simultaneously maintaining the floor area and geometry. This research explores new aerodynamic modification options for owners, architects, and structural engineers with the aim of better aerodynamic performance for high-rise buildings without compromising other design objectives. 

A prion-like RNA-binding protein, CPEB3, can regulate local translation in dendritic spines. CPEB3 monomers repress translation, whereas CPEB3 aggregates activate translation of its target mRNAs. However, the CPEB3 aggregates, as long-lasting prions, may raise the problem of unregulated translational activation. Here, we propose a computational model of the complex structure between CPEB3 RNA-binding domain (CPEB3-RBD) and small ubiquitin-like modifier protein 2 (SUMO2). Free energy calculations suggest that the allosteric effect of CPEB3-RBD/SUMO2 interaction can amplify the RNA-binding affinity of CPEB3. Combining with previous experimental observations on the SUMOylation mode of CPEB3, this model suggests an equilibrium shift of mRNA from binding to deSUMOylated CPEB3 aggregates to binding to SUMOylated CPEB3 monomers in basal synapses. This work shows how a burst of local translation in synapses can be silenced following a stimulation pulse, and explores the CPEB3/SUMO2 interplay underlying the structural change of synapses and the formation of long-term memories. 

Bacteriophage T7 gp4 helicase has served as a model system for understanding mechanisms of hexameric replicative helicase translocation. The mechanistic basis of how nucleoside 5′-triphosphate hydrolysis and translocation of gp4 helicase are coupled is not fully resolved. Here, we used a thermodynamically benchmarked coarse-grained protein force field, Associative memory, Water mediated, Structure and Energy Model (AWSEM), with the single-stranded DNA (ssDNA) force field 3SPN.2C to investigate gp4 translocation. We found that the adenosine 5′-triphosphate (ATP) at the subunit interface stabilizes the subunit–subunit interaction and inhibits subunit translocation. Hydrolysis of ATP to adenosine 5′-diphosphate enables the translocation of one subunit, and new ATP binding at the new subunit interface finalizes the subunit translocation. The LoopD2 and the N-terminal primase domain provide transient protein–protein and protein–DNA interactions that facilitate the large-scale subunit movement. The simulations of gp4 helicase both validate our coarse-grained protein–ssDNA force field and elucidate the molecular basis of replicative helicase translocation.