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Nguyen, H

Publications and source records attributed to Nguyen, H.

Cryo-electron microscopy structure of a zinc uptake ABC transporter

Zn2+ is an essential micronutrient required for many biological processes. Microorganisms employ high-affinity Zn2+ ABC transporters to take up zinc from the environment when it is scarce, yet the mechanism of zinc uptake and its regulation remain poorly understood. Here, we report the cryo-electron microscopy structure of the Zn2+ ABC transporter complex ZnuB-ZnuC from Escherichia coli. It contains two ZnuB transport and two ZnuC regulatory subunits. The ZnuB homodimer is in an outward-facing, closed conformation with a large hydrophilic cavity at the dimer interface. Each ZnuC subunit contains an N-terminal nucleotide-binding domain and a C-terminal zinc-sensing domain (ZSD). Zn2+ binding to the ZSD locks the transporter in a closed state, whereas under low-Zn2+ conditions, the disorder of ZSD permits ATP-driven zinc uptake. Zn2+ ABC transporters are ubiquitously utilized by pathogenic bacteria to compete with hosts for Zn2+. These findings reveal potential therapeutic targets for disrupting Zn2+ homeostasis in antibiotic-resistant pathogens.

59 BASIC BIOLOGICAL SCIENCES↗

Statistical projections for multi-dimensional visual data exploration

When working with large, multidimensional and multivariate data, science users are frequently interested in understanding variation in data, as opposed to the actual data values. Our work focuses on exploring how a simple statistical metric, the Coefficient of Variation (or Cv), can be used in several different ways to facilitate understanding variation in large data. As a statistical measure, it offers a key advantage over more widely accepted measures like standard deviation, namely to its ability to capture local variation properties. As a multidimensional projection operator, Cv is an effective way of reducing data size while preserving the key variational signal. Visualizations produced from Cv that target conveying variation in data are highly informative, especially compared to those produced with more widely known methods. We demonstrate these ideas within the context of a two-part application case study focusing on understanding long-Term trends in the the changes in precipitation and winds in large-scale climate model ensemble output.

Nguyen, H↗

SU-E-T-148: Benchmarks and Pre-Treatment Reviews: A Study of Quality Assurance Effectiveness

Purpose: To determine the impact benchmarks and pre-treatment reviews have on improving the quality of submitted clinical trial data. Methods: Benchmarks are used to evaluate a site’s ability to develop a treatment that meets a specific protocol’s treatment guidelines prior to placing their first patient on the protocol. A pre-treatment review is an actual patient placed on the protocol in which the dosimetry and contour volumes are evaluated to be per protocol guidelines prior to allowing the beginning of the treatment. A key component of these QA mechanisms is that sites are provided timely feedback to educate them on how to plan per the protocol and prevent protocol deviations on patients accrued to a protocol. For both benchmarks and pre-treatment reviews a dose volume analysis (DVA) was performed using MIM softwareTM. For pre-treatment reviews a volume contour evaluation was also performed. Results: IROC Houston performed a QA effectiveness analysis of a protocol which required both benchmarks and pre-treatment reviews. In 70 percent of the patient cases submitted, the benchmark played an effective role in assuring that the pre-treatment review of the cases met protocol requirements. The 35 percent of sites failing the benchmark subsequently modified there planning technique to pass the benchmark before being allowed to submit a patient for pre-treatment review. However, in 30 percent of the submitted cases the pre-treatment review failed where the majority (71 percent) failed the DVA. 20 percent of sites submitting patients failed to correct their dose volume discrepancies indicated by the benchmark case. Conclusion: Benchmark cases and pre-treatment reviews can be an effective QA tool to educate sites on protocol guidelines and to minimize deviations. Without the benchmark cases it is possible that 65 percent of the cases undergoing a pre-treatment review would have failed to meet the protocols requirements.Support: U24-CA-180803.

60 APPLIED LIFE SCIENCES↗

TU-G-BRD-06: The Imaging and Radiation Oncology Core Houston (IROC Houston) QA Center International Activities Outside North America

Purpose: To describe the extent of IROC Houston’s (formerly the RPC) QA activities and audit results for radiotherapy institutions outside of North America (NA). Methods: The IROC Houston’s QA program components were designed to audit the radiation dose calculation chain from the NIST traceable reference beam calibration, to inclusion of dosimetry parameters used to calculate tumor doses, to the delivery of the radiation dose. The QA program provided to international institutions includes: 1) remote TLD/OSLD audit of machine output, 2) credentialing for advanced technologies, and 3) review of patient treatment records. IROC Houston uses the same standards and acceptance criteria for all of its audits whether for North American or international sites. Results: IROC Houston’s QA program has reached out to radiotherapy sites in 43 different countries since 2013 through their participation in clinical trials. In the past two years, 2,778 international megavoltage beam outputs were audited with OSLD/TLD. While the average IROC/Inst ratio is near unity for all sites monitored, there are international regions whose results are significantly different from the NA region. In the past 2 years, 477 and 87 IMRT H&N phantoms were irradiated at NA and international sites, respectively. Regardless of the OSLD beam audit results, the overall pass rate (87 percent) for all international sites (no region separation) is equal to the NA sites. Of the 182 international patient charts reviewed, 10.7 percent of the dose calculation points did not meet our acceptance criterion as compared to 13.6 percent for NA sites. The lower pass rate for NA sites results from a much larger brachytherapy component which has been shown to be more error prone. Conclusion: IROC Houston has expanded its QA services worldwide and continues a long history of improving radiotherapy dose delivery in many countries. Funding received for QA audit services from the Korean GOG, DAHANCA, EORTC, ICON and CMIC Group.

60 APPLIED LIFE SCIENCES↗

The MOLLER Experiment: An Ultra-Precise Measurement of the Weak Mixing Angle Using Møller Scattering

The physics case and an experimental overview of the MOLLER (Measurement Of a Lepton Lepton Electroweak Reaction) experiment at the 12 GeV upgraded Jefferson Lab are presented. A highlight of the Fundamental Symmetries subfield of the 2007 NSAC Long Range Plan was the SLAC E158 measurement of the parity-violating asymmetry $A_{PV}$ in polarized electron-electron (M{\o}ller) scattering. The proposed MOLLER experiment will improve on this result by a factor of five, yielding the most precise measurement of the weak mixing angle at low or high energy anticipated over the next decade. This new result would be sensitive to the interference of the electromagnetic amplitude with new neutral current amplitudes as weak as $\sim 10^{-3}\cdot G_F$ from as yet undiscovered dynamics beyond the Standard Model. The resulting discovery reach is unmatched by any proposed experiment measuring a flavor- and CP-conserving process over the next decade, and yields a unique window to new physics at MeV and multi-TeV scales, complementary to direct searches at high energy colliders such as the Large Hadron Collider (LHC). The experiment takes advantage of the unique opportunity provided by the upgraded electron beam energy, luminosity, and stability at Jefferson Laboratory and the extensive experience accumulated in the community after a round of recent successfully completed parity-violating electron scattering experiments

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗