skip to main content

Search for: All records

Creators/Authors contains: "Douglas, R"

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. Abstract We present a spectroscopic analysis of the most rapidly rotating stars currently known, VFTS 102 ( v e sin i = 649 ± 52 km s −1 ; O9: Vnnne+) and VFTS 285 ( v e sin i = 610 ± 41 km s −1 ; O7.5: Vnnn), both members of the 30 Dor complex in the Large Magellanic Cloud. This study is based on high-resolution ultraviolet spectra from Hubble Space Telescope/Cosmic Origins Spectrograph and optical spectra from the Very Large Telescope (VLT) X-shooter plus archival VLT GIRAFFE spectra. We utilize numerical simulations of their photospheres, rotationally distorted shape, and gravity darkening to calculate model spectral line profiles and predicted monochromatic absolute fluxes. We use a guided grid search to investigate parameters that yield best fits for the observed features and fluxes. These fits produce estimates of the physical parameters for these stars (plus a Galactic counterpart, ζ Oph) including the equatorial rotational velocity, inclination, radius, mass, gravity, temperature, and reddening. We find that both stars appear to be radial-velocity constant. VFTS 102 is rotating at critical velocity, has a modest He enrichment, and appears to share the motion of the nearby OB-association LH 99. These properties suggest thatmore »the star was spun up through a close binary merger. VFTS 285 is rotating at 95% of critical velocity, has a strong He enrichment, and is moving away from the R136 cluster at the center of 30 Dor. It is mostly likely a runaway star ejected by a supernova explosion that released the components of the natal binary system.« less
    Free, publicly-accessible full text available May 1, 2023
  2. Cefotaximase-Munich (CTX-M) extended-spectrum beta-lactamases (ESBLs) are commonly associated with Gram-negative, hospital-acquired infections worldwide. Several beta-lactamase inhibitors, such as clavulanate, are used to inhibit the activity of these enzymes. To understand the mechanism of CTX-M-15 activity, we have determined the crystal structures of CTX-M-15 in complex with two specific classes of beta-lactam compounds, desfuroylceftiofur (DFC) and ampicillin, and an inhibitor, clavulanic acid. The crystal structures revealed that Ser70 and five other residues (Lys73, Tyr105, Glu166, Ser130, and Ser237) participate in catalysis and binding of those compounds. Based on analysis of steady-state kinetics, thermodynamic data, and molecular docking to both wild-type and S70A mutant structures, we determined that CTX-M-15 has a similar affinity for all beta-lactam compounds (ceftiofur, nitrocefin, DFC, and ampicillin), but with lower affinity for clavulanic acid. A catalytic mechanism for tested β-lactams and two-step inhibition mechanism of clavulanic acid were proposed. CTX-M-15 showed a higher activity toward DFC and nitrocefin, but significantly lower activity toward ampicillin and ceftiofur. The interaction between CTX-M-15 and both ampicillin and ceftiofur displayed a higher entropic but lower enthalpic effect, compared with DFC and nitrocefin. DFC, a metabolite of ceftiofur, displayed lower entropy and higher enthalpy than ceftiofur. This finding suggests that compounds containingmore »amine moiety (e.g., ampicillin) and the furfural moiety (e.g., ceftiofur) could hinder the hydrolytic activity of CTX-M-15.« less
    Free, publicly-accessible full text available May 1, 2023
  3. Newborn screening (NBS) is a state-level initiative that detects life-threatening genetic disorders for which early treatment can substantially improve health outcomes. Cystic fibrosis (CF) is among the most prevalent disorders in NBS. CF can be caused by a large number of mutation variants to the CFTR gene. Most states use a multitest CF screening process that includes a genetic test (DNA). However, due to cost concerns, DNA is used only on a small subset of newborns (based on a low-cost biomarker test with low classification accuracy), and only for a small subset of CF-causing variants. To overcome the cost barriers of expanded genetic testing, we explore a novel approach, of multipanel pooled DNA testing. This approach leads not only to a novel optimization problem (variant selection for screening, variant partition into multipanels, and pool size determination for each panel), but also to novel CF NBS processes. We establish key structural properties of optimal multipanel pooled DNA designs; develop a methodology that generates a family of optimal designs at different costs; and characterize the conditions under which a 1-panel versus a multipanel design is optimal. This methodology can assist decision-makers to design a screening process, considering the cost versus accuracy trade-off.more »Our case study, based on published CF NBS data from the state of New York, indicates that the multipanel and pooling aspects of genetic testing work synergistically, and the proposed NBS processes have the potential to substantially improve both the efficiency and accuracy of current practices. This paper was accepted by Stefan Scholtes, healthcare management.« less
    Free, publicly-accessible full text available March 14, 2023
  4. Abstract HD 93521 is a massive, rapidly rotating star that is located about 1 kpc above the Galactic disk, and the evolutionary age for its estimated mass is much less than the time of flight if it was ejected from the disk. Here we present a reassessment of both the evolutionary and kinematical timescales for HD 93521. We calculate a time of flight of 39 ± 3 Myr based upon the distance and proper motions from Gaia EDR3 and a summary of radial velocity measurements. We then determine the stellar luminosity using a rotational model combined with the observed spectral energy distribution and distance. A comparison with evolutionary tracks for rotating stars from Brott et al. yields an evolutionary age of about 5 ± 2 Myr. We propose that the solution to the timescale discrepancy is that HD 93521 is a stellar merger product. It was probably ejected from the Galactic disk as a close binary system of lower-mass stars that eventually merged to create the rapidly rotating and single massive star we observe today.
    Free, publicly-accessible full text available January 31, 2023
  5. Free, publicly-accessible full text available February 1, 2023
  6. Free, publicly-accessible full text available March 1, 2023
  7. Cystic fibrosis (CF) is a life-threatening genetic disorder. Early treatment of CF-positive newborns can extend life span, improve quality of life, and reduce healthcare expenditures. As a result, newborns are screened for CF throughout the United States. Genetic testing is costly; therefore, CF screening processes start with a relatively inexpensive but not highly accurate biomarker test. Newborns with elevated biomarker levels are further screened via genetic testing for a panel of variants (types of mutations), selected from among hundreds of CF-causing variants, and newborns with mutations detected are referred for diagnostic testing, which corrects any false-positive screening results. Conversely, a false negative represents a missed CF diagnosis and delayed treatment. Therefore, an important decision is which CF-causing variants to include in the genetic testing panel so as to reduce the probability of a false negative under a testing budget that limits the number of variants in the panel. We develop novel deterministic and robust optimization models and identify key structural properties of optimal genetic testing panels. These properties lead to efficient, exact algorithms and key insights. Our case study underscores the value of our optimization-based approaches for CF newborn screening compared with current practices. Our findings have important implications formore »public policy.« less
    Free, publicly-accessible full text available January 1, 2023
  8. A facile way to generate compatibilized blends of immiscible polymers is through reactive blending of end-functionalized homopolymers. The reaction may be reversible or irreversible depending on the end-groups and is affected by the immiscibility and transport of the reactant homopolymers and the compatibilizing copolymer product. Here we describe a phase-field framework to model the combined dynamics of reaction kinetics, diffusion, and multi-component thermodynamics on the evolution of the microstructure and reaction rate in reactive blending. A density functional with no fitting parameters, which is obtained by adapting a framework of Uneyama and Doi and qualitatively agrees with self-consistent field theory, is used in a diffusive dynamics model. For a symmetric mixture of equal-length reactive polymers mixed in equal proportions, we find that depending on the Flory χ parameter, the microstructure of an irreversibly reacting blend progresses through a rich evolution of morphologies, including from two-phase coexistence to a homogeneous mixture, or a two-phase to three-phase coexistence transitioning to a homogeneous blend or a lamellar copolymer. The emergence of a three-phase region at high χ leads to a previously unreported reaction rate scaling. For a reversible reaction, we find that the equilibrium composition is a function of both the equilibrium constantmore »for the reaction and the χ parameter. We demonstrate that phase-field models are an effective way to understand the complex interplay of thermodynamic and kinetic effects in a reacting polymer blend.« less
    Free, publicly-accessible full text available January 26, 2023
  9. Free, publicly-accessible full text available December 1, 2022
  10. Free, publicly-accessible full text available April 14, 2023