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  1. Free, publicly-accessible full text available November 1, 2023
  2. Abstract Failure of modularity remains a significant challenge for assembling synthetic gene circuits with tested modules as they often do not function as expected. Competition over shared limited gene expression resources is a crucial underlying reason. It was reported that resource competition makes two seemingly separate genes connect in a graded linear manner. Here we unveil nonlinear resource competition within synthetic gene circuits. We first build a synthetic cascading bistable switches (Syn-CBS) circuit in a single strain with two coupled self-activation modules to achieve two successive cell fate transitions. Interestingly, we find that the in vivo transition path was redirected as the activation of one switch always prevails against the other, contrary to the theoretically expected coactivation. This qualitatively different type of resource competition between the two modules follows a ‘winner-takes-all’ rule, where the winner is determined by the relative connection strength between the modules. To decouple the resource competition, we construct a two-strain circuit, which achieves successive activation and stable coactivation of the two switches. These results illustrate that a highly nonlinear hidden interaction between the circuit modules due to resource competition may cause counterintuitive consequences on circuit functions, which can be controlled with a division of labor strategy.

    Binaries consisting of a hot subdwarf star and an accreting white dwarf (WD) are sources of gravitational wave radiation at low frequencies and possible progenitors of Type Ia supernovae if the WD mass is large enough. Here, we report the discovery of the third binary known of this kind: It consists of a hot subdwarf O (sdO) star and a WD with an orbital period of 3.495 h and an orbital shrinkage of 0.1 s in 6 yr. The sdO star overfills its Roche lobe and likely transfers mass to the WD via an accretion disc. From spectroscopy, we obtain an effective temperature of $T_{\mathrm{eff}}=54\, 240\pm 1840$ K and a surface gravity of log g = 4.841 ± 0.108 for the sdO star. From the light curve analysis, we obtain an sdO mass of MsdO = 0.55 M⊙ and a mass ratio of q = MWD/MsdO = 0.738 ± 0.001. Also, we estimate that the disc has a radius of $\sim\!0.41\ \mathrm{R}_\odot$ and a thickness of $\sim\!0.18\ \mathrm{R}_\odot$. The origin of this binary is probably a common envelope ejection channel, where the progenitor of the sdO star is either a red giant branch star or, more likely, an early asymptotic giant branch star; the sdO star will subsequently evolve intomore »a WD and merge with its WD companion, likely resulting in an R Coronae Borealis (R CrB) star. The outstanding feature in the spectrum of this object is strong Ca H&K lines, which are blueshifted by ∼200 km s−1 and likely originate from the recently ejected common envelope, and we estimated that the remnant common envelope (CE) material in the binary system has a density $\sim\!6\times 10^{-10}\ {\rm g\, cm}^{-3}$.

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  4. Abstract Interdependent critical infrastructures in coastal regions, including transportation, electrical grid, and emergency services, are continually threatened by storm-induced flooding. This has been demonstrated a number of times, most recently by hurricanes such as Harvey and Maria, as well as Sandy and Katrina. The need to protect these infrastructures with robust protection mechanisms is critical for our continued existence along the world’s coastlines. Planning these protections is non-trivial given the rare-event nature of strong storms and climate change manifested through sea level rise. This article proposes a framework for a methodology that combines multiple computational models, stakeholder interviews, and optimization to find an optimal protective strategy over time for critical coastal infrastructure while being constrained by budgetary considerations.
  5. Growth-mediated feedback between synthetic gene circuits and host organisms leads to diverse emerged behaviors, including growth bistability and enhanced ultrasensitivity. However, the range of possible impacts of growth feedback on gene circuits remains underexplored. Here we mathematically and experimentally demonstrated that growth feedback affects the functions of memory circuits in a network topology-dependent way. Specifically, the memory of the self-activation switch is quickly lost due to the growth-mediated dilution of the circuit products. Decoupling of growth feedback reveals its memory, manifested by its hysteresis property across a broad range of inducer concentration. On the contrary, the toggle switch is more refractory to growth-mediated dilution and can retrieve its memory after the fast-growth phase. The underlying principle lies in the different dependence of active and repressive regulations in these circuits on the growth-mediated dilution. Our results unveil the topology-dependent mechanism on how growth-mediated feedback influences the behaviors of gene circuits.
  6. Abstract

    Achieving adequate healing in large or load‐bearing bone defects is highly challenging even with surgical intervention. The clinical standard of repairing bone defects using autografts or allografts has many drawbacks. A bioactive ceramic scaffold, strontium‐hardystonite‐gahnite or “Sr‐HT‐Gahnite” (a multi‐component, calcium silicate‐based ceramic) is developed, which when 3D‐printed combines high strength with outstanding bone regeneration ability. In this study, the performance of purely synthetic, 3D‐printed Sr‐HT‐Gahnite scaffolds is assessed in repairing large and load‐bearing bone defects. The scaffolds are implanted into critical‐sized segmental defects in sheep tibia for 3 and 12 months, with bone autografts used for comparison. The scaffolds induce substantial bone formation and defect bridging after 12 months, as indicated by X‐ray, micro‐computed tomography, and histological and biomechanical analyses. Detailed analysis of the bone‐scaffold interface using focused ion beam scanning electron microscopy and multiphoton microscopy shows scaffold degradation and maturation of the newly formed bone. In silico modeling of strain energy distribution in the scaffolds reveal the importance of surgical fixation and mechanical loading on long‐term bone regeneration. The clinical application of 3D‐printed Sr‐HT‐Gahnite scaffolds as a synthetic bone substitute can potentially improve the repair of challenging bone defects and overcome the limitations of bone graft transplantation.