skip to main content

Search for: All records

Creators/Authors contains: "King, David"

Note: When clicking on a Digital Object Identifier (DOI) number, you will be taken to an external site maintained by the publisher. Some full text articles may not yet be available without a charge during the embargo (administrative interval).
What is a DOI Number?

Some links on this page may take you to non-federal websites. Their policies may differ from this site.

  1. We report the synthesis of quaternary (di)cationic triamantane derivatives G1 and G3 by the permethylation of the corresponding primary ammonium ions G2 and G4. The complexation behaviors of G1–G4 toward CB[7] and CB[8] were examined by 1 H NMR spectroscopy, which reveals that CB[8] is capable of fully encapsulating G1–G4 whereas CB[7] forms inclusion complexes with G1, G2, and G4 but cannot fully encapsulate the central hydrophobic core of the bis-quaternary ammonium ion G3. The geometries of the CB[ n ]-guest complexes were determined by analyzing the complexation induced changes in chemical shifts and were further confirmed by molecular modelling using the Conformer–Rotamer Ensemble Sampling Tool (CREST) based on the GFN methods. Finally, the complexation thermodynamics were determined by a combination of 1 H NMR competitive experiments, direct isothermal titration calorimetry (ITC) measurements, and competitive ITC titrations using a tight binding ternary complex as a competitor.
    Free, publicly-accessible full text available March 13, 2024
  2. Abstract

    ELT-2 is the major transcription factor (TF) required for Caenorhabditis elegans intestinal development. ELT-2 expression initiates in embryos to promote development and then persists after hatching through the larval and adult stages. Though the sites of ELT-2 binding are characterized and the transcriptional changes that result from ELT-2 depletion are known, an intestine-specific transcriptome profile spanning developmental time has been missing. We generated this dataset by performing Fluorescence Activated Cell Sorting on intestine cells at distinct developmental stages. We analyzed this dataset in conjunction with previously conducted ELT-2 studies to evaluate the role of ELT-2 in directing the intestinal gene regulatory network through development. We found that only 33% of intestine-enriched genes in the embryo were direct targets of ELT-2 but that number increased to 75% by the L3 stage. This suggests additional TFs promote intestinal transcription especially in the embryo. Furthermore, only half of ELT-2's direct target genes were dependent on ELT-2 for their proper expression levels, and an equal proportion of those responded to elt-2 depletion with over-expression as with under-expression. That is, ELT-2 can either activate or repress direct target genes. Additionally, we observed that ELT-2 repressed its own promoter, implicating new models for its autoregulation.more »Together, our results illustrate that ELT-2 impacts roughly 20–50% of intestine-specific genes, that ELT-2 both positively and negatively controls its direct targets, and that the current model of the intestinal regulatory network is incomplete as the factors responsible for directing the expression of many intestinal genes remain unknown.

    « less
  3. We report the molecular recognition properties of Pillar[ n ]MaxQ (P[ n ]MQ) toward a series of (methylated) amino acids, amino acid amides, and post-translationally modified peptides by a combination of 1 H NMR, isothermal titration calorimetry, indicator displacement assays, and molecular dynamics simulations. We find that P6MQ is a potent receptor for N -methylated amino acid side chains. P6MQ recognized the H3K4Me 3 peptide with K d = 16 nM in phosphate buffered saline.
    Free, publicly-accessible full text available September 28, 2023
  4. Free, publicly-accessible full text available October 1, 2023
  5. Evans, Christopher J. ; Bryant, Julia J. ; Motohara, Kentaro (Ed.)
  6. Abstract Pilot projects have emerged in cities globally as a way to experiment with the utilization of a suite of smart mobility and emerging transportation technologies. Automated vehicles (AVs) have become central tools for such projects as city governments and industry explore the use and impact of this emerging technology. This paper presents a large-scale assessment of AV pilot projects in U.S. cities to understand how pilot projects are being used to examine the risks and benefits of AVs, how cities integrate these potentially transformative technologies into conventional policy and planning, and how and what they are learning about this technology and its future opportunities and risks. Through interviews with planning practitioners and document analysis, we demonstrate that the approaches cities take for AVs differ significantly, and often lack coherent policy goals. Key findings from this research include: (1) a disconnect between the goals of the pilot projects and a city’s transportation goals; (2) cities generally lack a long-term vision for how AVs fit into future mobility systems and how they might help address transportation goals; (3) an overemphasis of non-transportation benefits of AV pilots projects; (4) AV pilot projects exhibit a lack of policy learning and iteration; and (5)more »cities are not leveraging pilot projects for public benefits. Overall, urban and transportation planners and decision makers show a clear interest to discover how AVs can be used to address transportation challenges in their communities, but our research shows that while AV pilot projects purport to do this, while having numerous outcomes, they have limited value for informing transportation policy and planning questions around AVs. We also find that AV pilot projects, as presently structured, may constrain planners’ ability to re-think transportation systems within the context of rapid technological change.« less
  7. Abstract Low complexity domains (LCDs) in proteins are regions predominantly composed of a small subset of the possible amino acids. LCDs are involved in a variety of normal and pathological processes across all domains of life. Existing methods define LCDs using information-theoretical complexity thresholds, sequence alignment with repetitive regions, or statistical overrepresentation of amino acids relative to whole-proteome frequencies. While these methods have proven valuable, they are all indirectly quantifying amino acid composition, which is the fundamental and biologically-relevant feature related to protein sequence complexity. Here, we present a new computational tool, LCD-Composer, that directly identifies LCDs based on amino acid composition and linear amino acid dispersion. Using LCD-Composer's default parameters, we identified simple LCDs across all organisms available through UniProt and provide the resulting data in an accessible form as a resource. Furthermore, we describe large-scale differences between organisms from different domains of life and explore organisms with extreme LCD content for different LCD classes. Finally, we illustrate the versatility and specificity achievable with LCD-Composer by identifying diverse classes of LCDs using both simple and multifaceted composition criteria. We demonstrate that the ability to dissect LCDs based on these multifaceted criteria enhances the functional mapping and classification of LCDs.