A Macromolecular Approach to Eradicate Multidrug Resistant Bacterial Infections while Mitigating Drug Resistance Onset

Polymyxins remain the last line treatment for multidrug-resistant (MDR) infections. As polymyxins resistance emerges, there is an urgent need to develop effective antimicrobial agents capable of mitigating MDR. Here, we report biodegradable guanidinium-functionalized polycarbonates with a distinctive mechanism that does not induce drug resistance. Unlike conventional antibiotics, repeated use of the polymers does not lead to drug resistance. Transcriptomic analysis of bacteria further supports development of resistance to antibiotics but not to the macromolecules after 30 treatments. Importantly, high in vivo treatment efficacy of the macromolecules is achieved in MDR A. baumannii-, E. coli-, K. pneumoniae-, methicillin-resistant S. aureus-, cecal ligation and puncture-induced polymicrobial peritonitis, and P. aeruginosa lung infection mouse models while remaining non-toxic (e.g., therapeutic index—ED50/LD50: 1473 for A. baumannii infection). These biodegradable synthetic macromolecules have been demonstrated to have broad spectrum in vivo antimicrobial activity, and have excellent potential as systemic antimicrobials against MDR infections

A Wireless Sensor Network Based Personnel Positioning Scheme in Coal Mines with Blind Areas

This paper proposes a novel personnel positioning scheme for a tunnel network with blind areas, which compared with most existing schemes offers both low-cost and high-precision. Based on the data models of tunnel networks, measurement networks and mobile miners, the global positioning method is divided into four steps: (1) calculate the real time personnel location in local areas using a location engine, and send it to the upper computer through the gateway; (2) correct any localization errors resulting from the underground tunnel environmental interference; (3) determine the global three-dimensional position by coordinate transformation; (4) estimate the personnel locations in the blind areas. A prototype system constructed to verify the positioning performance shows that the proposed positioning system has good reliability, scalability, and positioning performance. In particular, the static localization error of the positioning system is less than 2.4 m in the underground tunnel environment and the moving estimation error is below 4.5 m in the corridor environment. The system was operated continuously over three months without any failures

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

A hybridization of granular adaptive tabu search with path relinking for the multi-depot open vehicle routing problem

The multi-depot open vehicle routing problem (MDOVRP) differs from the classical VRP in that there is more than one depot and the vehicle does not need to return to a depot after serving the last customer. For solving this challenging problem, we propose a hybrid metaheuristic algorithm (GATS-PR) which integrates the granular adaptive tabu search with path relinking. The main contributions of this work consist of introducing a solution-based tabu search technique in granular tabu search, designing an adaptive neighborhood selection method for the large neighborhoods with 22 kinds of move types, and adopting path relinking with a new similarity definition to the MDOVRP for the first time. Computational results on 24 public instances demonstrate that GATS-PR outperforms the previous state-of-the-art algorithms in the literature. Specifically, GATS-PR improved and matched the previous best known results on 4 and 19 instances, respectively

Ultraviolet-Irradiated All-Organic Nanocomposites with Polymer Dots for High-Temperature Capacitive Energy Storage

Highlights All-organic polymer composites for high-temperature capacitive energy storage. Zero-dimensional polymer dots with high electron affinity are used as fillers. Deep charge traps from UV-irradiated films reduce the high-field conduction loss

Bacaryolanes A–C, Rare Bacterial Caryolanes from a Mangrove Endophyte

Caryolanes are known as typical plant-derived sesquiterpenes. Here we describe the isolation and full structure elucidation of three caryolanes, bacaryolane A–C (<b>1</b>–<b>3</b>), that are produced by a bacterial endophyte (<i>Streptomyces</i> sp. JMRC:ST027706) of the mangrove plant <i>Bruguiera gymnorrhiza.</i> By 2D NMR, analysis of the first X-ray crystallographic data of a caryolane (bacaryolane C), CD spectroscopy, and comparison with data for plant-derived caryolanes, we rigorously established the absolute configuration of the bacaryolanes and related compounds from bacteria. Bacterial caryolanes appear as the mirror images of typical plant caryolanes. Apparently plant and bacteria harbor stereodivergent biosynthetic pathways, which may be used as metabolic signatures. The discovery of plant-like volatile terpenes in endophytes not only is an important addition to the bacterial terpenome but may also point to complex molecular interactions in the plant–microbe association