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At least 235 records · Page 13

Interrogation of the Burkholderia pseudomallei genome to address differential virulence among isolates

Infection by the Gram-negative pathogen Burkholderia pseudomallei results in the disease melioidosis, acquired from the environment in parts of southeast Asia and northern Australia. Clinical symptoms of melioidosis range from acute (fever, pneumonia, septicemia, and localized infection) to chronic (abscesses in various organs and tissues, most commonly occurring in the lungs, liver, spleen, kidney, prostate and skeletal muscle), and persistent infections in humans are difficult to cure. Understanding the basic biology and genomics of B. pseudomallei is imperative for the development of new vaccines and therapeutic interventions. This formidable task is becoming more tractable due to the increasing number of B. pseudomallei genomes that are being sequenced and compared. Here, we compared three B. pseudomallei genomes, from strains MSHR668, K96243 and 1106a, to identify features that might explain why MSHR668 is more virulent than K96243 and 1106a in a mouse model of B. pseudomallei infection. Our analyses focused on metabolic, virulence and regulatory genes that were present in MSHR668 but absent from both K96243 and 1106a. We also noted features present in K96243 and 1106a but absent from MSHR668, and identified genomic differences that may contribute to variations in virulence noted among the three B. pseudomallei isolates. While this work contributes to our understanding of B. pseudomallei genomics, more detailed experiments are necessary to characterize the relevance of specific genomic features to B. pseudomallei metabolism and virulence. Functional analyses of metabolic networks, virulence and regulation shows promise for examining the effects of B. pseudomallei on host cell metabolism and will lay a foundation for future prediction of the virulence of emerging strains. Continued emphasis in this area will be critical for protection against melioidosis, as a better understanding of what constitutes a fully virulent Burkholderia isolate may provide for better diagnostic and medical countermeasure strategies.

59 BASIC BIOLOGICAL SCIENCES↗

Using Imaging Methods to Interrogate Radiation-Induced Cell Signaling

There is increasing emphasis on the use of systems biology approaches to define radiation induced responses in cells and tissues. Such approaches frequently rely on global screening using various high throughput 'omics' platforms. Although these methods are ideal for obtaining an unbiased overview of cellular responses, they often cannot reflect the inherent heterogeneity of the system or provide detailed spatial information. Additionally, performing such studies with multiple sampling time points can be prohibitively expensive. Imaging provides a complementary method with high spatial and temporal resolution capable of following the dynamics of signaling processes. In this review, we utilize specific examples to illustrate how imaging approaches have furthered our understanding of radiation induced cellular signaling. Particular emphasis is placed on protein co-localization, and oscillatory and transient signaling dynamics.

59 BASIC BIOLOGICAL SCIENCES↗

Active Neutron Interrogation of Non-Radiological Materials with the Nuclear Materials Identification System

The Nuclear Materials Identification System (NMIS) at Oak Ridge National Laboratory (ORNL), although primarily designed for analyzing special nuclear material, is capable of identifying nonradiological materials with a wide range of measurement techniques. This report demonstrates four different measurement methods, complementary to fast-neutron imaging, which can be used for material identification: DT transmission, DT scattering, californium transmission, and active time-tagged gamma spectroscopy. Each of the four techniques was used to evaluate how these methods can be used to identify four materials: aluminum, polyethylene, graphite, and G-10 epoxy. While such measurements have been performed individually in the past, in this project, all four measurements were performed on the same set of materials. The results of these measurements agree well with predicted results. In particular, the results of the active gamma spectroscopy measurements demonstrate the technique's applicability in a future version of NMIS which will incorporate passive and active gamma-ray spectroscopy. This system, designated as a fieldable NMIS (FNMIS), is under development by the US Department of Energy Office of Nuclear Verification.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗

Cadmium Subtraction Method for the Active Albedo Neutron Interrogation of Uranium

This report describes work performed under the Next Generation Safeguards Initiative (NGSI) Cadmium Subtraction Project. The project objective was to explore the difference between the traditional cadmium (Cd) ratio signature and a proposed alternative Cd subtraction (or Cd difference) approach. The thinking behind the project was that a Cd subtraction method would provide a more direct measure of multiplication than the existing Cd ratio method. At the same time, it would be relatively insensitive to changes in neutron detection efficiency when properly calibrated. This is the first published experimental comparison and evaluation of the Cd ratio and Cd subtraction methods.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗

Research Projects for Interrogations of Biological Systems: Training for the Development of Novel Radiotracers

This grant was situated at the University of Missouri to train Ph.D. scientists in radiochemistry and synthetic chemistry in conjunction with Faculty from the Interdisciplinary Plant Group, Division of Biological Sciences, the MU Research Reactor Center, Molecular Biology and the Radiopharmaceutical Sciences Institute. This project was collaborative with Brookhaven National Laboratory (Richard Ferrieri, PI). Projects for the Ph.D. candidates included novel probe development for peptides, nucleosides, small molecules or radiometals, the direct use of radiometals as probes, or nuclear techniques for analysis. The projects for the postdoctoral fellow involved synthetic chemistry for the preparation of precursors for novel tracers that will be radiolabeled with 18 F or other appropriate radionuclides. The skill sets of our team members allowed us to prepare probes with positron or single photon emitters, as well as ones that are dual-labeled (fluorescent and radiolabeled). We focused our technical advances to those that will be broadly applicable to any research field.

38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEA↗

Light Water Reactor Sustainability Program Interrogation of Alkali-Silica Reaction Degraded Concrete Samples using Acoustic and Thermal Techniques to Support Development of a Structural Health Monitoring Framework

Assessment and management of aging concrete structures in nuclear power plants require a more systematic approach than simple reliance on existing code margins of safety. Health monitoring of concrete structures is performed to understand the current condition of a structure based on heterogeneous measurements and then produce high-confidence actionable information regarding structural integrity. This information can then be used to support operational and maintenance decisions. The proposed diagnosis and prognosis framework consists of four elements: health monitoring, data analytics, uncertainty quantification, and prognosis. The objectives of this ongoing research project focuses on health monitoring and data analytics of concrete slab cast, which is cured using four pockets of reactive aggregates: pure silica, wells, placitas, and spratt. A controlled concrete slab with four aggregates is cast at Vanderbilt University in representative conditions to accelerate degradation due to alkali-silica reaction (ASR). Four nondestructive evaluation (NDE) techniques (thermography, mechanical deformation measurements, nonlinear impact resonance-acoustic spectroscopy, and vibro-acoustic modulation) are used to examine the degraded concrete slab. Heterogeneous data from these techniques are analyzed for assessing ASRrelated degradation in concrete samples. In addition, this report discusses thermography assessment of three cement bricks cured under different conditions to accelerate ASR-related degradation. The application of the digital image correlation technique to study ASR-related degradation on a large concrete sample at the University of Tennessee Knoxville is discussed and initial observations are presented in this report. The results from the data analysis of the NDE techniques on concrete slab cured at Vanderbilt University are discussed in detail in this report. The major outcome of the analysis suggests that the nonlinear impact resonance acoustic spectroscopy is able to detect potential degradation in a concrete slab but is unable to locate or isolate the degradation. Alternatively, the vibro-acoustic technique is able to detect degradation and locate the damage in the concrete slab cast. The outcomes supports development of a structural health monitoring framework.

22 GENERAL STUDIES OF NUCLEAR REACTORS↗

Correlated Neutron Interrogation Source in the Active Well [Slides]

The Active Well Coincidence Counter (AWCC) is a technology developed by Los Alamos National Laboratories for the use of non-destructive assay of Uranium materials for international nuclear inspectorates such as the IAEA.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

The Dynamic Response of Polymers Interrogated by 3rd Generation X-ray Light Sources

Future predictive models of materials response under extreme conditions will be increasingly phaseand microstructure-aware. As such, model development and validation will require new types of experimental data that probe responses at lattice-to-mesoscales in real time during dynamic events. High brilliance X-ray light sources coupled to dynamic driver platforms offer tremendous potential for providing new insights into the physics of materials under dynamic conditions. Over the last several years, data from burgeoning facilities are already challenging historical model assumptions in several areas.

36 MATERIALS SCIENCE↗

Development of Membrane Platforms to Interrogate Host-Pathogen Interactions

Membrane fusion is a critical step in enveloped virus entry and infection; however, molecular understanding of enveloped virus entry and treatment options remain limited. In recent decades, advances in imaging have facilitated the development of methods to study single virus events and membrane organization providing insight towards entry mechanisms. Through these advances, membrane composition and organization have been shown to play a critical role in the entry process. This LDRD uses model membrane platforms and basic biophysics to investigate entry mechanisms of enveloped viruses and understand membrane-based delivery technologies. This team has established foundations for using membrane-based platforms and biophysical techniques at Sandia to characterize membrane fusion.

59 BASIC BIOLOGICAL SCIENCES↗

Genetic tools to optimize lignocellulose conversion in anaerobic fungi and interrogate their genomes. Final Report

The project advances the development of anaerobic fungi, emerging model organisms for the deconstruction and conversion of untreated lignocellulosic feedstocks. Anaerobic fungi are native to the digestive tracts of large ruminants that are central to lignocellulose degradation, degrading more than 50% of the biomass by weight with similar efficiency regardless of lignin composition, which can inhibit other fungi.

09 BIOMASS FUELS↗

Neutron Multiplicity Counting Diagnosis of Uranium Assemblies Interrogated by Cf-252 [Poster]

Researchers concluded: First neutron multiplicity counting of tens of kilograms of 235 U with organic scintillators; leakage multiplication estimates to be improved by incorporating detector cross-talk; provides data comparison for “Multiplicity Theory Beyond the Point Model;" promotes continued use of organic scintillators for NCERC and elsewhere.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗