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Creators/Authors contains: "Short, Andrew E"

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  1. Abstract Here we present a technology to facilitate synthetic memory in a living system via repurposing Transcriptional Programming (i.e., our decision-making technology) parts, to regulate (intercept) recombinase function post-translation. We show that interception synthetic memory can facilitate programmable loss-of-function via site-specific deletion, programmable gain-of-function by way of site-specific inversion, and synthetic memory operations with nested Boolean logical operations. We can expand interception synthetic memory capacity more than 5-fold for a single recombinase, with reconfiguration specificity for multiple sites in parallel. Interception synthetic memory is ~10-times faster than previous generations of recombinase-based memory. We posit that the faster recombination speed of our next-generation memory technology is due to the post-translational regulation of recombinase function. This iteration of synthetic memory is complementary to decision-making via Transcriptional Programming – thus can be used to develop intelligent synthetic biological systems for myriad applications. 
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  2. Marvaldi, Adriana (Ed.)
    Abstract Tailoring ultraconserved element (UCE) probe set design to focal taxa has been demonstrated to improve locus recovery and phylogenomic inference. However, beyond conducting expensive in vitro testing, it remains unclear how best to determine whether an existing UCE probe set is likely to suffice for phylogenomic inference or whether tailored probe design will be desirable. Here we investigate the utility of 8 different UCE probe sets for the in silico phylogenomic inference of scarabaeoid beetles. Probe sets tested differed in terms of (i) how phylogenetically distant from Scarabaeoidea taxa those used during probe design are, (ii) breadth of phylogenetic inference probe set was designed for, and (iii) method of probe design. As part of this study, 2 new UCE probe sets are produced for the beetle family Scarabaeidae and superfamily Hydrophiloidea. We confirm that probe set utility decreases with increasing phylogenetic distance from target taxa. In addition, narrowing the phylogenetic breadth of probe design decreases the phylogenetic capture range. We also confirm previous findings regarding ways to optimize UCE probe design. Finally, we make suggestions regarding assessment of need for de novo probe design. 
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  3. Homogeneous molecular catalysts are valued for their reaction specificity but face challenges in manufacturing scale-up due to complexities in final product separation, catalyst recovery, and instability in the presence of water. Heterogenizing these molecular catalysts, by attachment to a solid support, could transform the practical utility of molecular catalysts, simplify catalyst separation and recovery, and prevent catalyst decomposition by impeding bimolecular catalyst interactions. Previous strategies to heterogenize molecular catalysts via ligand-first binding to supports have suffered from reduced catalytic activity and leaching (loss) of catalyst, especially in environmentally friendly solvents like water. Herein, we describe an approach in which molecular catalysts are first attached to a metal oxide support through acidic ligands and then “encapsulated” with a metal oxide layer via atomic layer deposition (ALD) to prevent molecular detachment from the surface. For this initial report, which is based upon the well-studied Suzuki carbon–carbon cross-coupling reaction, we demonstrate the ability to achieve catalytic performance using a non-noble metal molecular catalyst in high aqueous content solvents. The catalyst chosen exhibits limited catalytic reactivity under homogeneous conditions due to extremely short catalyst lifetimes, but when heterogenized and immobilized with an optimal ALD layer thickness product yields >90% can be obtained in primarily aqueous solutions. Catalyst characterization before and after ALD application and catalytic reaction is achieved with infrared, electron paramagnetic resonance, and X-ray spectroscopies. 
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