Browsing by Author "Zhang, Tong"
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- Demonstrating a Comprehensive Wastewater-Based Surveillance Approach That Differentiates Globally Sourced ResistomesPrieto Riquelme, Maria Virginia; Garner, Emily; Gupta, Suraj; Metch, Jake; Zhu, Ni; Blair, Matthew F.; Arango-Argoty, Gustavo; Maile-Moskowitz, Ayella; Li, An-dong; Flach, Carl-Fredrik; Aga, Diana S.; Nambi, Indumathi M.; Larsson, D. G. Joakim; Bürgmann, Helmut; Zhang, Tong; Pruden, Amy; Vikesland, Peter J. (ACS, 2022-06-27)Wastewater-based surveillance (WBS) for disease monitoring is highly promising but requires consistent methodologies that incorporate predetermined objectives, targets, and metrics. Herein, we describe a comprehensive metagenomics-based approach for global surveillance of antibiotic resistance in sewage that enables assessment of 1) which antibiotic resistance genes (ARGs) are shared across regions/communities; 2) which ARGs are discriminatory; and 3) factors associated with overall trends in ARGs, such as antibiotic concentrations. Across an internationally sourced transect of sewage samples collected using a centralized, standardized protocol, ARG relative abundances (16S rRNA gene-normalized) were highest in Hong Kong and India and lowest in Sweden and Switzerland, reflecting national policy, measured antibiotic concentrations, and metal resistance genes. Asian versus European/US resistomes were distinct, with macrolide-lincosamide-streptogramin, phenicol, quinolone, and tetracycline versus multidrug resistance ARGs being discriminatory, respectively. Regional trends in measured antibiotic concentrations differed from trends expected from public sales data. This could reflect unaccounted uses, captured only by the WBS approach. If properly benchmarked, antibiotic WBS might complement public sales and consumption statistics in the future. The WBS approach defined herein demonstrates multisite comparability and sensitivity to local/regional factors.
- Designing Practical Software Bug Detectors Using Commodity Hardware and Common Programming PatternsZhang, Tong (Virginia Tech, 2020-01-13)Software bugs can cost millions and affect people's daily lives. However, many bug detection tools are not always practical in reality, which hinders their wide adoption. There are three main concerns regarding existing bug detectors: 1) run-time overhead in dynamic bug detectors, 2) space overhead in dynamic bug detectors, and 3) scalability and precision issues in static bug detectors. With those in mind, we propose to: 1) leverage commodity hardware to reduce run-time overhead, 2) reuse metadata maintained by one bug detector to detect other types of bugs, reducing space overhead, and 3) apply programming idioms to static analyses, improving scalability and precision. We demonstrate the effectiveness of three approaches using data race bugs, memory safety bugs, and permission check bugs, respectively. First, we leverage the commodity hardware transactional memory (HTM) selectively to use the dynamic data race detector only if necessary, thereby reducing the overhead from 11.68x to 4.65x. We then present a production-ready data race detector, which only incurs a 2.6% run-time overhead, by using performance monitoring units (PMUs) for online memory access sampling and offline unsampled memory access reconstruction. Second, for memory safety bugs, which are more common than data races, we provide practical temporal memory safety on top of the spatial memory safety of the Intel MPX in a memory-efficient manner without additional hardware support. We achieve this by reusing the existing metadata and checks already available in the Intel MPX-instrumented applications, thereby offering full memory safety at only 36% memory overhead. Finally, we design a scalable and precise function pointer analysis tool leveraging indirect call usage patterns in the Linux kernel. We applied the tool to the detection of permission check bugs; the detector found 14 previously unknown bugs within a limited time budget.
- Electrical conduction transport mechanisms of barium titanate- based multilayer ceramic capacitorsZhang, Tong (Virginia Tech, 1988-08-15)The major objectives of this study were to examine electrical conduction properties of BaTiO3-based multilayer ceramic ( MLC ) capacitors in order to gain a better understanding of the conduction transport mechanisms inside the devices. The experiments involved mainly leakage current versus time measurements under both low temperature-low voltage stress and high temperature-high voltage stress. It was established that leakage current conduction in a MLC capacitor under temperature-voltage stress can be divided into three different conduction regions due to different mechanisms. Those regions are polarization current, DC conduction current and degradation current. The polarization current decreases with time as a power law relation, i.e. Ic(t) t-m where the exponent value m is strongly dependent on the type of capacitor and temperature, but is only weakly dependent on the applied voltage. It has been proposed that two degradation models ( a charge carrier concentration model and a reduction of grain boundary barrier height model ) can explain the degradation behavior for the Z5U devices tested. Degradation measurements indicate that the lifetime for Z5U capacitors can be described by Minford's expression. However, these models account only partly for X7R degradation. X7R behavior, is characterized by an early power law time dependence, followed by exponential voltage dependence. The most probable conduction transport mechanism in X7R capacitors is small polaron hopping, while grain boundary transmission may be the predominant conduction transport mechanism in Z5U capacitors.
- Long-read metagenomic sequencing reveals shifts in associations of antibiotic resistance genes with mobile genetic elements from sewage to activated sludgeDai, Dongjuan; Brown, Connor L.; Bürgmann, Helmut; Larsson, D. G. J.; Nambi, Indumathi; Zhang, Tong; Flach, Carl-Fredrik; Pruden, Amy; Vikesland, Peter J. (2022-01-29)Background There is concern that the microbially rich activated sludge environment of wastewater treatment plants (WWTPs) may contribute to the dissemination of antibiotic resistance genes (ARGs). We applied long-read (nanopore) sequencing to profile ARGs and their neighboring genes to illuminate their fate in the activated sludge treatment by comparing their abundance, genetic locations, mobility potential, and bacterial hosts within activated sludge relative to those in influent sewage across five WWTPs from three continents. Results The abundances (gene copies per Gb of reads, aka gc/Gb) of all ARGs and those carried by putative pathogens decreased 75–90% from influent sewage (192-605 gc/Gb) to activated sludge (31-62 gc/Gb) at all five WWTPs. Long reads enabled quantification of the percent abundance of ARGs with mobility potential (i.e., located on plasmids or co-located with other mobile genetic elements (MGEs)). The abundance of plasmid-associated ARGs decreased at four of five WWTPs (from 40–73 to 31–68%), and ARGs co-located with transposable, integrative, and conjugative element hallmark genes showed similar trends. Most ARG-associated elements decreased 0.35–13.52% while integrative and transposable elements displayed slight increases at two WWTPs (1.4–2.4%). While resistome and taxonomic compositions both shifted significantly, host phyla for chromosomal ARG classes remained relatively consistent, indicating vertical gene transfer via active biomass growth in activated sludge as the key pathway of chromosomal ARG dissemination. Conclusions Overall, our results suggest that the activated sludge process acted as a barrier against the proliferation of most ARGs, while those that persisted or increased warrant further attention.
- Metagenomic Analysis of Antibiotic Resistance Genes in Dairy Cow Feces following Therapeutic Administration of Third Generation CephalosporinChambers, Lindsey R.; Yang, Ying; Littier, Heather; Ray, Partha P.; Zhang, Tong; Pruden, Amy; Strickland, Michael S.; Knowlton, Katharine F. (PLOS, 2015-08-10)Although dairy manure is widely applied to land, it is relatively understudied compared to other livestock as a potential source of antibiotic resistance genes (ARGs) to the environment and ultimately to human pathogens. Ceftiofur, the most widely used antibiotic used in U.S. dairy cows, is a 3rd generation cephalosporin, a critically important class of antibiotics to human health. The objective of this study was to evaluate the effect of typical ceftiofur antibiotic treatment on the prevalence of ARGs in the fecal microbiome of dairy cows using a metagenomics approach. β-lactam ARGs were found to be elevated in feces from Holstein cows administered ceftiofur (n = 3) relative to control cows (n = 3). However, total numbers of ARGs across all classes were not measurably affected by ceftiofur treatment, likely because of dominance of unaffected tetracycline ARGs in the metagenomics libraries. Functional analysis via MG-RAST further revealed that ceftiofur treatment resulted in increases in gene sequences associated with “phages, prophages, transposable elements, and plasmids”, suggesting that this treatment also enriched the ability to horizontally transfer ARGs. Additional functional shifts were noted with ceftiofur treatment (e.g., increase in genes associated with stress, chemotaxis, and resistance to toxic compounds; decrease in genes associated with metabolism of aromatic compounds and cell division and cell cycle), along with measureable taxonomic shifts (increase in Bacterioidia and decrease in Actinobacteria). This study demonstrates that ceftiofur has a broad, measureable and immediate effect on the cow fecal metagenome. Given the importance of 3rd generation cephalospirins to human medicine, their continued use in dairy cattle should be carefully considered and waste treatment strategies to slow ARG dissemination from dairy cattle manure should be explored.