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Bacterial antimicrobial resistance (AMR) is among the most significant challenges to current human society. Exposing bacteria to antibiotics can activate their self- saving responses, e.g., filamentation, leading to the development of bacterial AMR. Understanding the molecular changes during the self- saving responses can reveal new inhibition methods of drug- resistant bacteria. Herein, we used an online microfluidics mass spectrometry system for real- time characterization of metabolic changes of bacteria during filamentation under the stimulus of antibiotics. Significant pathways, e.g., nucleotide metabolism and coenzyme A biosynthesis, correlated to the filamentation of extended- spectrum beta- lactamase- producing Escherichia coli (ESBL- E. coli) were identified. A cyclic dinucleotide, c- di- GMP, which is derived from nucleotide metabolism and reported closely related to bacterial resistance and tolerance, was observed significantly up- regulated during the bacterial filamentation. By using a chemical inhibitor, ebselen, to inhibit diguanylate cyclases which catalyzes the synthesis of c- di- GMP, the minimum inhibitory concentration of ceftriaxone against ESBL- E. coli was significantly decreased. This inhibitory effect was also verified with other ESBL- E. coli strains and other beta- lactam antibiotics, i.e., ampicillin. A mutant strain of ESBL- E. coli by knocking out the dgcM gene was used to demonstrate that the inhibition of the antibiotic resistance to beta- lactams by ebselen was mediated through the inhibition of the diguanylate cyclase DgcM and the modulation of c- di- GMP levels. Our study uncovers the molecular changes during bacterial filamentation and proposes a method to inhibit antibiotic- resistant bacteria by combining traditional antibiotics and chemical inhibitors against the enzymes involved in bacterial self- saving responses. [ABSTRACT FROM AUTHOR]

We present new images and continuum spectral analysis for 14 resolved Galactic supernova remnants (SNRs) selected from the 74 MHz Very Large Array Low-Frequency Sky Survey Redux (VLSSr). We combine new integrated measurements from the VLSSr with, when available, flux densities extracted from the Galactic and Extragalactic All-Sky Murchison Widefield Array Survey and measurements from the literature to generate improved integrated continuum spectra sampled from ~15 MHz to ~217 GHz. We present the VLSSr images. When possible we combine them with publicly available images at 1.4 GHz, to analyse the resolved morphology and spectral index distribution across each SNR. We interpret the results and look for evidence of thermal absorption caused by ionised gas either proximate to the SNR itself, or along its line of sight. Three of the SNRs, G4.5+6.8 (Kepler), G28.6−0.1, and G120.1+1.4 (Tycho), have integrated spectra which can be adequately fit with simple power laws. The resolved spectral index map for Tycho confirms internal absorption which was previously detected by the Low Frequency Array, but it is insufficient to affect the fit to the integrated spectrum. Two of the SNRs are pulsar wind nebulae, G21.5−0.9 and G130.7+3.1 (3C 58). For those we identify high-frequency spectral breaks at 38 and 12 GHz, respectively. For the integrated spectra of the remaining nine SNRs, a low frequency spectral turnover is necessary to adequately fit the data. In all cases we are able to explain the turnover by extrinsic thermal absorption. For G18.8+0.3 (Kes 67), G21.8−0.6 (Kes 69), G29.7−0.3 (Kes 75), and G41.1−0.3 (3C 397), we attribute the absorption to ionised gas along the line of sight, possibly from extended H II region envelopes. For G23.3−0.3 (W41) the absorption can be attributed to H II regions located in its immediate proximity. Thermal absorption from interactions at the ionised interface between SNR forward shocks and the surrounding medium were previously identified as responsible for the low frequency turnover in SNR G31.9+0.0 (3C 391); our integrated spectrum is consistent with the previous results. We present evidence for the same phenomenon in three additional SNRs G27.4+0.0 (Kes 73), G39.2–0.3 (3C 396), and G43.3–0.2 (W49B), and derive constraints on the physical properties of the interaction. This result indicates that interactions between SNRs and their environs should be readily detectable through thermal absorption by future low frequency observations of SNRs with improved sensitivity and resolution. [ABSTRACT FROM AUTHOR]

Context. Cosmic rays (CRs) and magnetic fields are dynamically important components in the Galaxy, and their energy densities are comparable to that of the turbulent interstellar gas. The interaction of CRs and Galactic magnetic fields (GMF) produces synchrotron radiation clearly visible in the radio regime. Detailed measurements of synchrotron radiation averaged over the line-of-sight (LOS), so-called synchrotron emissivities, can be used as a tracer of the CR density and GMF strength. Aims. Our aim is to model the synchrotron emissivity in the Milky Way using a three-dimensional dataset instead of LOS-integrated intensity maps on the sky. Methods. Using absorbed HII regions, we measured the synchrotron emissivity over a part of the LOS through the Galaxy, changing from a two-dimensional to a three-dimensional view. Performing these measurements on a large scale is one of the new applications of the window opened by current low-frequency arrays. Using various simple axisymmetric emissivity models and a number of GMF-based emissivity models, we were able to simulate the synchrotron emissivities and compare them to the observed values in the catalog. Results. We present a catalog of low-frequency absorption measurements of HII regions, their distances and electron temperatures, compiled from literature. These data show that the axisymmetric emissivity models are not complex enough, but the GMF-based emissivity models deliver a reasonable fit. These models suggest that the fit can be improved by either an enhanced synchrotron emissivity in the outer reaches of the Milky Way or an emissivity drop near the Galactic center. Conclusions. Current GMF models plus a constant CR density model cannot explain low-frequency absorption measurements, but the fits improved with slight (ad hoc) adaptations. It is clear that more detailed models are needed, but the current results are very promising. [ABSTRACT FROM AUTHOR]

Recent studies compared the age effects and birth cohort effects on female invasive breast cancer ( FIBC) incidence in Asian populations with those in the US white population. They were based on age-period-cohort model extrapolation and estimated annual percentage change ( EAPC) in the age-standardized incidence rates ( ASR). It is of interest to examine these results based on cohort-specific annual percentage change in rate ( APCR) by age and without age-period-cohort model extrapolation. FIBC data (1991-2010) were obtained from the Taiwan Cancer Registry and the U.S. SEER 9 registries. APCR based on smoothed Lexis diagrams were constructed to study the age, period, and cohort effects on FIBC incidence. The patterns of age-specific rates by birth cohort are similar between Taiwan and the US. Given any age-at-diagnosis group, cohort-specific rates increased overtime in Taiwan but not in the US; cohort-specific APCR by age decreased with birth year in both Taiwan and the US but was always positive and large in Taiwan. Given a diagnosis year, APCR decreased as birth year increased in Taiwan but not in the US. In Taiwan, the proportion of APCR attributable to cohort effect was substantial and that due to case ascertainment was becoming smaller. Although our study shows that incidence rates of FIBC have increased rapidly in Taiwan, thereby confirming previous results, the rate of increase over time is slowing. Continued monitoring of APCR and further investigation of the cause of the APCR decrease in Taiwan are warranted. [ABSTRACT FROM AUTHOR]

We report the detection and observed characteristics of giant pulses from the Crab Nebula pulsar (B0531+21) in four frequency bands covering 20-84 MHz using the recently completed LongWavelength Array Station 1 (LWA1) radio telescope. In 10 hr of observations distributed over a 72 day period in fall of 2012, 33 giant pulses having peak flux densities between 400 Jy and 2000 Jy were detected. Twenty-two of these pulses were detected simultaneously in channels of 16 MHz bandwidth centered at 44 MHz, 60 MHz, and 76 MHz, including one pulse which was also detected in a channel centered at 28 MHz.We quantify statistics of pulse amplitude and pulse shape characteristics, including pulse broadening. Amplitude statistics are consistent with expectations based on extrapolations from previous work at higher and lower frequencies. Pulse broadening is found to be relatively high, but not significantly greater than expected.We present procedures that have been found to be effective for observing giant pulses in this frequency range. [ABSTRACT FROM AUTHOR]

ABSTRACT We present parametrized broad-band spectral models valid at frequencies between 30 and 300 MHz for six bright radio sources selected from the 3C survey, spread in right ascension from 0 to 24 h. For each source, data from the literature are compiled and tied to a common flux density scale. These data are then used to parametrize an analytic polynomial spectral calibration model. The optimal polynomial order in each case is determined using the ratio of the Bayesian evidence for the candidate models. Maximum likelihood parameter values for each model are presented, with associated errors, and the percentage error in each model as a function of frequency is derived. These spectral models are intended as an initial reference for science from the new generation of low-frequency telescopes now coming online, with particular emphasis on the Low Frequency Array (LOFAR). [ABSTRACT FROM AUTHOR]

Objective. Use of cancer cases from registries and PMSI claims database to estimate Département-specific incidence of four major cancers. Methods. Case extraction used principal diagnosis then surgery codes. PMSI cases/registry cases ratios for 2004 were modelled then Département-specific incidence for 2007 estimated using these ratios and 2007 PMSI cases. Results. For 2007, only colon-rectum and breast cancer estimations were satisfactorily validated for infranational incidence not ovary and kidney cancers. For breast, the estimated national incidence was 50,578 cases and the incidence rate 98.6 cases per 100,000 person per year. For colon-rectum, incidence was 21,172 in men versus 18,327 in women and the incidence rate 38 per 100,000 versus 24.8. For ovary, the estimated incidence was 4,637 and the rate 8.6 per 100,000. For kidney, incidence was 6,775 in men versus 3,273 in women and the rate 13.3 per 100.000 versus 5.2. Conclusion. Incidence estimation using PMSI patient identifiers proved encouraging though still dependent on the assumption of uniform cancer treatments and coding. [ABSTRACT FROM AUTHOR]

The system A amino acid transporter is encoded by three members of the Slc38 gene family, giving rise to three subtypes: Nat-coupled neutral amino acid transporter (SNAT)1, SNAT2, and SNAT4. SNAT2 is expressed ubiquitously in mammalian tissues; SNAT1 is predominantly expressed in heart, brain, and placenta; and SNAT4 is reported to be expressed solely by the liver. In the placenta, system A has an essential role in the supply of neutral amino acids needed for fetal growth. In the present study, we examined expression and localization of SNAT1, SNAT2, and SNAT4 in human placenta during gestation. Real-time quantitative PCR was used to examine steady-state levels of system A subtype mRNA in early (6-10 wk) and late (10-13 wk) first-trimester and full-term (38-40 wk) placentas. We detected mRNA for all three isoforms from early gestation onward. There were no differences in SNAT1 and SNAT2 mRNA expression with gestation. However, SNAT4 mRNA expression was significantly higher early in the first trimester compared with the full-term placenta (P < 0.01). We next investigated SNAT4 protein expression in human placenta. In contrast to the observation for gene expression, Western blot analysis revealed that SNAT4 protein expression was significantly higher at term compared with the first trimester (P < 0.05). Immunohistochemistry and Western blot analysis showed that SNAT4 is localized to the microvillous and basal plasma membranes of the syncytiotrophoblast, suggesting a role for this isoform of system A in amino acid transport across the placenta. This study therefore provides the first evidence of SNAT4 mRNA and protein expression in the human placenta, both at the first trimester and at full term. [ABSTRACT FROM AUTHOR]

We present a large survey of giant pulses from the Crab Pulsar as observed with the first station of the Long Wavelength Array. Automated methods for detecting giant pulses at low frequencies where scattering becomes prevalent are also explored. More than 1400 pulses were detected across four frequency bands between 20 and 84 MHz over a seven-month period beginning in 2013, with additional followup observations in late 2014 and early 2015. A handful of these pulses were detected simultaneously across all four frequency bands. We examine pulse characteristics, including pulse broadening and power law indices for amplitude distributions. We find that the flux density increases toward shorter wavelengths, consistent with a spectral turnover at 100 MHz. Our observations uniquely span multiple scattering epochs, manifesting as a notable trend in the number of detections per observation. These results are characteristic of the variable interface between the synchrotron nebula and the surrounding interstellar medium. [ABSTRACT FROM AUTHOR]