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We employ the WRF-Chem model to study summertime air pollution, the intense photochemical activity and their impact on air quality over the eastern Mediterranean. We utilize three nested domains with horizontal resolutions of 80, 16 and 4 km, with the finest grid focusing on the island of Cyprus, where the CYPHEX campaign took place in July 2014. Anthropogenic emissions are based on the EDGAR HTAP global emission inventory, while dust and biogenic emissions are calculated online. Three simulations utilizing the CBMZ-MOSAIC, MOZART-MOSAIC, and RADM2-MADE/SORGAM gas-phase and aerosol mechanisms are performed. The results are compared with measurements from a dense observational network of 14 ground stations in Cyprus. The model simulates T2 m, Psurf, and WD10 m accurately, with minor differences in WS10 m between model and observations at coastal and mountainous stations attributed to limitations in the representation of the complex topography in the model. It is shown that the south-eastern part of Cyprus is mostly affected by emissions from within the island, under the dominant (60 %) westerly flow during summertime. Clean maritime air from the Mediterranean can reduce concentrations of local air pollutants over the region during westerlies. Ozone concentrations are overestimated by all three mechanisms (9 % ≤ NMB ≤ 23 %) with the smaller mean bias (4.25 ppbV) obtained by the RADM2-MADE/SORGAM mechanism. Differences in ozone concentrations can be attributed to the VOC treatment by the three mechanisms. The diurnal variability of pollution and ozone precursors is not captured (hourly correlation coefficients for O3 ≤ 0.29). This might be attributed to the underestimation of NOx concentrations by local emissions by up to 50 %. For the fine particulate matter (PM2.5), the lowest mean bias (9 µg m−3) is obtained with the RADM2-MADE/SORGAM mechanism, with overestimates in sulfate and ammonium aerosols. Overestimation of sulfate aerosols by this mechanism may be linked to the SO2 oxidation in clouds. The MOSAIC aerosol mechanism overestimates PM2.5 concentrations by up to 22 µg m−3 due to a more pronounced dust component compared to the other two mechanisms, mostly influenced by the dust inflow from the global model. We conclude that all three mechanisms are very sensitive to boundary conditions from the global model for both gas-phase and aerosol pollutants, in particular dust and ozone.

Glutathione (GSH) is a ubiquitous tripeptide that is biosynthesized in situ at high concentrations (1–5 mM) and involved in the regulation of cellular homeostasis via multiple mechanisms. The main known action of GSH is its antioxidant capacity, which aids in maintaining the redox cycle of cells. To this end, GSH peroxidases contribute to the scavenging of various forms of ROS and RNS. A generally underestimated mechanism of action of GSH is its direct nucleophilic interaction with electrophilic compounds yielding thioether GSH S-conjugates. Many compounds, including xenobiotics (such as NAPQI, simvastatin, cisplatin, and barbital) and intrinsic compounds (such as menadione, leukotrienes, prostaglandins, and dopamine), form covalent adducts with GSH leading mainly to their detoxification. In the present article, we wish to present the key role and significance of GSH in cellular redox biology. This includes an update on the formation of GSH-S conjugates or GSH adducts with emphasis given to the mechanism of reaction, the dependence on GST (GSH S-transferase), where this conjugation occurs in tissues, and its significance. The uncovering of the GSH adducts’ formation enhances our knowledge of the human metabolome. GSH–hematin adducts were recently shown to have been formed spontaneously in multiples isomers at hemolysates, leading to structural destabilization of the endogenous toxin, hematin (free heme), which is derived from the released hemoglobin. Moreover, hemin (the form of oxidized heme) has been found to act through the Kelch-like ECH associated protein 1 (Keap1)–nuclear factor erythroid 2-related factor-2 (Nrf2) signaling pathway as an epigenetic modulator of GSH metabolism. Last but not least, the implications of the genetic defects in GSH metabolism, recorded in hemolytic syndromes, cancer and other pathologies, are presented and discussed under the framework of conceptualizing that GSH S-conjugates could be regarded as signatures of the cellular metabolism in the diseased state.

Although several studies have examined the role of home literacy environment (HLE) in learning to read in Western societies, little is known about the role of HLE in Chinese reading. In addition, the few studies in Chinese have not tested the possible effects of HLE on reading comprehension. Thus, the purpose of this study was to examine the direct and indirect effects of different aspects of HLE (formal literacy experiences, informal literacy experiences, and access to literacy resources) on reading comprehension in Chinese. One hundred fifty-nine third year kindergarten children (70 girls and 89 boys; Mage = 72.62 months) participated in the study. In kindergarten, they were assessed on emergent literacy skills (vocabulary, phonological awareness, pinyin knowledge, rapid naming), in Grade 1, on word reading, and, in Grade 2, on reading comprehension. In addition, parents filled out a questionnaire on their education and income, the frequency of different HLE activities, the number of children’s books at home, and their expectations, when their children were in kindergarten. Results of structural equation modeling showed that formal literacy experiences predicted reading comprehension through the effects of pinyin knowledge on word reading. Access to literacy resources predicted reading comprehension through the effects of rapid naming, phonological awareness, and vocabulary. Finally, informal literacy experiences did not predict any of the emergent literacy skills or reading outcomes. Our findings provide only partial support of the home literacy model and suggest that the culture in which environmental effects take place may determine what aspects of the home literacy environment contribute to children’s reading performance and what not.

Several studies have shown that intelligence is a significant correlate of academic achievement [...].Several studies have shown that intelligence is a significant correlate of academic achievement [...].

Soil organic carbon (SOC) regulates terrestrial ecosystem functioning, provides diverse energy sources for soil microorganisms, governs soil structure, and regulates the availability of organically bound nutrients. Investigators in increasingly diverse disciplines recognize how quantifying SOC attributes can provide insight about ecological states and processes. Today, multiple research networks collect and provide SOC data, and robust, new technologies are available for managing, sharing, and analyzing large data sets. We advocate that the scientific community capitalize on these developments to augment SOC data sets via standardized protocols. We describe why such efforts are important and the breadth of disciplines for which it will be helpful, and outline a tiered approach for standardized sampling of SOC and ancillary variables that ranges from simple to more complex. We target scientists ranging from those with little to no background in soil science to those with more soil-related expertise, and offer examples of the ways in which the resulting data can be organized, shared, and discoverable.

We examined the longitudinal predictors of nonword decoding, reading fluency, and spelling in three languages that vary in orthographic depth: Finnish, Greek, and English. Eighty-two English-speaking, 70 Greek, and 88 Finnish children were followed from the age of 5.5 years old until Grade 2. Prior to any reading instruction, they were administered measures of phonological awareness, letter knowledge, and rapid naming speed. In Grade 2, they were administered measures of nonword decoding, text-reading fluency, and spelling. The results showed that the model for nonword decoding in Greek was similar to that of Finnish (both have consistent grapheme-to-phoneme mappings) while the model for spelling in Greek was similar to that of English (both have some inconsistent phoneme-to-grapheme mappings). In addition, the models for nonword decoding and spelling in Finnish were similar, because Finnish is consistent in both directions. Letter knowledge dominated the prediction in each language. The predictable role of orthographic consistency on literacy acquisition is discussed.

Current theoretical interpretations of naming speed and the research literature on its relation to reading are reviewed in this article. The authors examine naming speed's effects across languages and the shape of its relationship to reading. Also considered is the double-deficit hypothesis, by which students with both slow naming speed and low phonological awareness are hypothesized to be most at-risk for reading disability. Finally, the instructional literature regarding attempts to improve naming speed and use of naming speed as a predictor of response to intervention is reviewed. The authors conclude that naming speed is uniquely associated with a range of reading tasks across orthographies, and that early identification would be improved by the inclusion of naming speed measures. The poor response to instruction of students who have slow naming speed should be considered when designing interventions. Further work is required to specify the theoretical nature of naming speed and to determine how to help students with slow naming speed.

We recently reported that SF2312 ((1,5-dihydroxy-2-oxopyrrolidin-3-yl)phosphonic acid), a phosphonate antibiotic with a previously unknown mode of action, is a potent inhibitor of the glycolytic enzyme, Enolase. SF2312 can only be synthesized as a racemic-diastereomeric mixture. However, co-crystal structures with Enolase 2 (ENO2) have consistently shown that only the (3S,5S)-enantiomer binds to the active site. The acidity of the alpha proton at C-3, which deprotonates under mildly alkaline conditions, results in racemization; thus while the separation of four enantiomeric intermediates was achieved via chiral High Performance Liquid Chromatography (HPLC) of the fully protected intermediate, deprotection inevitably nullified enantiopurity. To prevent epimerization of the C-3, we designed and synthesized MethylSF2312, ((1,5-dihydroxy-3-methyl-2-oxopyrrolidin-3-yl)phosphonic acid), which contains a fully-substituted C-3 alpha carbon. As a racemic-diastereomeric mixture, MethylSF2312 is equipotent to SF2312 in enzymatic and cellular systems against Enolase. Chiral HPLC separation of a protected MethylSF2312 precursor resulted in the efficient separation of the four enantiomers. After deprotection and inevitable re-equilibration of the anomeric C-5, (3S)-MethylSF2312 was up to 2000-fold more potent than (3R)-MethylSF2312 in an isolated enzymatic assay. This observation strongly correlates with biological activity in both human cancer cells and bacteria for the 3S enantiomer of SF2312. Novel X-ray structures of human ENO2 with chiral and racemic MethylSF2312 show that only (3S,5S)-enantiomer occupies the active site. Enolase inhibition is thus a direct result of binding by the (3S,5S)-enantiomer of MethylSF2312. Concurrent with these results for MethylSF2312, we contend that the (3S,5S)-SF2312 is the single active enantiomer of inhibitor SF2312.

Molecular imaging is the visual representation of biological processes that take place at the cellular or molecular level in living organisms. To date, molecular imaging plays an important role in the transition from conventional medical practice to precision medicine. Among all imaging modalities, positron emission tomography (PET) has great advantages in sensitivity and the ability to obtain absolute imaging quantification after corrections for photon attenuation and scattering. Due to the ability to label a host of unique molecules of biological interest, including endogenous, naturally occurring substrates and drug-like compounds, the role of PET has been well established in the field of molecular imaging. In this article, we provide an overview of the recent advances in the development of PET radiopharmaceuticals and their clinical applications in oncology.

To better understand sources of uncertainty in projections of terrestrial carbon cycle feedbacks, we present an approach to separate the controls on modeled carbon changes. We separate carbon changes into four categories using a linearized, equilibrium approach: those arising from changed inputs (productivity-driven changes), and outputs (turnover-driven changes), of both the live and dead carbon pools. Using Coupled Model Intercomparison Project Phase 5 (CMIP5) simulations for five models, we find that changes to the live pools are primarily explained by productivity-driven changes, with only one model showing large compensating changes to live carbon turnover times. For dead carbon pools, the situation is more complex as all models predict a large reduction in turnover times in response to increases in productivity. This response arises from the common representation of a broad spectrum of decomposition turnover times via a multi-pool approach, in which flux-weighted turnover times are faster than mass-weighted turnover times. This leads to a shift in the distribution of carbon among dead pools in response to changes in inputs, and therefore a transient but long-lived reduction in turnover times. Since this behavior, a reduction in inferred turnover times resulting from an increase in inputs, is superficially similar to priming processes, but occurring without the mechanisms responsible for priming, we call the phenomenon \"false priming\", and show that it masks much of the intrinsic changes to dead carbon turnover times as a result of changing climate. These patterns hold across the fully coupled, biogeochemically coupled, and radiatively coupled 1 % yr−1 increasing CO2 experiments. We disaggregate inter-model uncertainty in the globally integrated equilibrium carbon responses to initial turnover times, initial productivity, fractional changes in turnover, and fractional changes in productivity. For both the live and dead carbon pools, inter-model spread in carbon changes arising from initial conditions is dominated by model disagreement on turnover times, whereas inter-model spread in carbon changes from fractional changes to these terms is dominated by model disagreement on changes to productivity in response to both warming and CO2 fertilization. However, the lack of changing turnover time control on carbon responses, for both live and dead carbon pools, in response to the imposed forcings may arise from a common lack of process representation behind changing turnover times (e.g., allocation and mortality for live carbon; permafrost, microbial dynamics, and mineral stabilization for dead carbon), rather than a true estimate of the importance of these processes.