Terrestrial biosphere changes over the last 120 kyr

A new global synthesis and biomization of long (> 40 kyr) pollen-data records is presented and used with simulations from the HadCM3 and FAMOUS climate models and the BIOME4 vegetation model to analyse the dynamics of the global terrestrial biosphere and carbon storage over the last glacial–interglacial cycle. Simulated biome distributions using BIOME4 driven by HadCM3 and FAMOUS at the global scale over time generally agree well with those inferred from pollen data. Global average areas of grassland and dry shrubland, desert, and tundra biomes show large-scale increases during the Last Glacial Maximum, between ca. 64 and 74 ka BP and cool substages of Marine Isotope Stage 5, at the expense of the tropical forest, warm-temperate forest, and temperate forest biomes. These changes are reflected in BIOME4 simulations of global net primary productivity, showing good agreement between the two models. Such changes are likely to affect terrestrial carbon storage, which in turn influences the stable carbon isotopic composition of seawater as terrestrial carbon is depleted in 13C

Mixed-effects models for health care longitudinal data with an informative visiting process: A Monte Carlo simulation study.

Electronic health records are being increasingly used in medical research to answer more relevant and detailed clinical questions; however, they pose new and significant methodological challenges. For instance, observation times are likely correlated with the underlying disease severity: Patients with worse conditions utilise health care more and may have worse biomarker values recorded. Traditional methods for analysing longitudinal data assume independence between observation times and disease severity; yet, with health care data, such assumptions unlikely hold. Through Monte Carlo simulation, we compare different analytical approaches proposed to account for an informative visiting process to assess whether they lead to unbiased results. Furthermore, we formalise a joint model for the observation process and the longitudinal outcome within an extended joint modelling framework. We illustrate our results using data from a pragmatic trial on enhanced care for individuals with chronic kidney disease, and we introduce user-friendly software that can be used to fit the joint model for the observation process and a longitudinal outcome

Terahertz spectroscopy of explosives and drugs

Terahertz frequency radiation possesses a unique combination of desirable properties for noninvasive imaging and spectroscopy of materials. This includes the ability to obtain chemical and structural information about substances concealed within dry packaging, such as paper, plastics, and cardboard. As a result, the application of terahertz frequency spectroscopy for the sensing and identification of materials of security interest, such as explosives and, to a lesser extent, drugs-of-abuse, has caught the attention of a number of researchers and security agencies. We describe terahertz time-domain spectroscopy and examine the terahertz spectra of a wide range of drugs-of-abuse, pure explosives, and plastic explosives

Measuring commitment to physical activity

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A Mutation in Escherichia coli DNA Gyrase Conferring Quinolone Resistance Results in Sensitivity to Drugs Targeting Eukaryotic Topoisomerase II

Fluoroquinolones are broad-spectrum antimicrobial agents that target type II topoisomerases. Many fluoroquinolones are highly specific for bacterial type II topoisomerases and act against both DNA gyrase and topoisomerase IV. In Escherichia coli, mutations causing quinolone resistance are often found in the gene that encodes the A subunit of DNA gyrase. One common site for resistance-conferring mutations alters Ser(83), and mutations to Leu or Trp result in high levels of resistance to fluoroquinolones. In the present study we demonstrate that the mutation of Ser(83) to Trp in DNA gyrase (Gyr(S83W)) also results in sensitivity to agents that are potent inhibitors of eukaryotic topoisomerase II but that are normally inactive against prokaryotic enzymes. Epipodophyllotoxins, such as etoposide, teniposide and amino-azatoxin, inhibited the DNA supercoiling activity of Gyr(S83W), and the enzyme caused elevated levels of DNA cleavage in the presence of these agents. The DNA sequence preference for Gyr(S83W)-induced cleavage sites in the presence of etoposide was similar to that seen with eukaryotic type II topoisomerases. Introduction of the Gyr(S83W) mutation in E. coli strain RFM443-242 by site-directed mutagenesis sensitized it to epipodophyllotoxins and amino-azatoxin. Our results demonstrate that sensitivity to agents that target topoisomerase II is conserved between prokaryotic and eukaryotic enzymes, suggesting that drug interaction domains are also well conserved and likely occur in domains important for the biochemical activities of the enzymes