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Background: Fibrinogen plays an essential role in blood coagulation and inflammation. Circulating fibrinogen levels may be determined based on interindividual differences in DNA methylation at cytosine-phosphate-guanine (CpG) sites and vice versa. Objectives: To perform an EWAS to examine an association between blood DNA methylation levels and circulating fibrinogen levels to better understand its biological and pathophysiological actions. Methods: We performed an epigenome-wide association study of circulating fibrinogen levels in 18 037 White, Black, American Indian, and Hispanic participants, representing 14 studies from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium. Circulating leukocyte DNA methylation was measured using the Illumina 450K array in 12 904 participants and using the EPIC array in 5133 participants. In each study, an epigenome-wide association study of fibrinogen was performed using linear mixed models adjusted for potential confounders. Study-specific results were combined using array-specific meta-analysis, followed by cross-replication of epigenome-wide significant associations. We compared models with and without CRP adjustment to examine the role of inflammation. Results: We identified 208 and 87 significant CpG sites associated with fibrinogen levels from the 450K (p < 1.03 × 10−7) and EPIC arrays (p < 5.78 × 10−8), respectively. There were 78 associations from the 450K array that replicated in the EPIC array and 26 vice versa. After accounting for overlapping sites, there were 83 replicated CpG sites located in 61 loci, of which only 4 have been previously reported for fibrinogen. The examples of genes located near these CpG sites were SOCS3 and AIM2, which are involved in inflammatory pathways. The associations of all 83 replicated CpG sites were attenuated after CRP adjustment, although many remained significant. Conclusion: We identified 83 CpG sites associated with circulating fibrinogen levels. These associations are partially driven by inflammatory pathways shared by both fibrinogen and CRP.

BaCe$_{0.25}$Mn$_{0.75}$O$_{3-\delta}$ (BCM), a non-stoichiometric oxide closely resembling a perovskite crystal structure, has recently emerged as a prospective contender for application in renewable energy harvesting by solar thermochemical hydrogen generation. Using solar energy, oxygen-vacancies can be created in BCM and the reduced crystal so obtained can, in turn, produce H2 by stripping oxygen from H2O. Therefore, a first step toward understanding the working mechanism and optimizing the performance of BCM, is a thorough and comparative analysis of the electronic structure of the pristine and the reduced material. In this paper, we probe the electronic structure of BCM using the combined effort of first-principles calculations and experimental O K-edge x-ray absorption spectroscopy (XAS). The computed projected density-of-states (PDOS) and orbital-plots are used to propose a simplified model for orbital-mixing between the oxygen and the ligand atoms. With the help of state-of-the-art simulations, we are able to find the origins of the XAS peaks and to categorize them on the basis of contribution from Ce and Mn. For the reduced crystal, the calculations show that, as a consequence of dielectric screening, the change in electron-density resulting from the reduction is strongly localized around the oxygen vacancy. Our experimental studies reveal a marked lowering of the first O K-edge peak in the reduced crystal which is shown to result from a diminished O-2p contribution to the frontier unoccupied orbitals, in accordance with the tight-binding scheme. Our study paves the way for investigation of the working-mechanism of BCM and for computational and experimental efforts aimed at design and discovery of efficient water-splitting oxides.

We demonstrate pOH imaging with confocal microscopy to probe the microenvironment of an operating CO2 reduction gas diffusion electrode. We find that the micrometer-scale morphology plays an important role in defining the CO2 reduction performance.

Solar thermochemical hydrogen production (STCH) via redox-active metal oxides is an approach for direct solar-driven hydrogen generation typically using a high-temperature redox cycle involving refractory oxides and steam. Typical cycles involve high-temperature reduction of oxides to form oxygen vacancies, followed by lower temperature reaction between oxygen vacancies and steam where the oxide is re-oxidized and the steam is reduced to hydrogen. Only a few materials have demonstrated reversible cycling under the typically harsh STCH conditions (e.g. 1500°C reduction, 900°C re-oxidation) and critical questions remain on the true reversibility of non-stoichiometric multi-cation oxide systems, significantly hampered by the lack of single-phase samples for these material systems. To date, most STCH processes have relied on CeO2 as a benchmark active material, but more recently, the 12R phase of BaCe0.25Mn0.75O3 (BCM) has demonstrated greater hydrogen-generation potential at lower peak temperatures. However, previous reports of 12R-BCM have included large fractions, > 10 wt%, of secondary phases, which complicate analysis of the stability and performance. A comprehensive understanding of the redox mechanism and reversibility of the process in BCM can only be achieved with nearly single-phase samples which, to date, have been difficult to produce. Here two approaches to BCM synthesis are reported: solid state and sol–gel-based routes. It is demonstrated that both routes can be tuned to produce the 12R structure with > 97 wt% yield when annealed ≥1450°C. Herein synchrotron-based diffraction measurements of rhombohedral 12R-BCM enabled characterization of the anisotropy between thermal expansion along the c-axis and within the ab plane. The impact of high-temperature redox cycling on the stability and phase fraction of the 12R-BCM polytype was also investigated. These results offer two viable routes for synthesis of high-purity 12R-BCM critically needed for evaluating the efficacy of BCM as a STCH material and validate its ability to split water at lower temperatures over extended numbers of redox cycles.

Organizations are increasingly called upon to solve complex problems in changing conditions that require the combined knowledge, skills, perspectives, and efforts of multiple individuals. These dynamic situations often require dynamic team composition. Dynamic team composition is sometimes thought of as synonymous to changes in membership, however, we contend that it also can occur through other means including team member development, the alignment between team member capabilities and the team's tasks, and changes in the accessibility to team member capabilities. Given the lack of overarching theories to organize and provide guidance on research and practice related to dynamic team composition, we take an interdisciplinary approach and leverage the fundamental concepts of potential and kinetic energy as a guiding framework to integrate the disparate literatures on dynamic team composition. We bring dynamic team composition to the forefront and delineate four types of dynamic team composition through

Three stocks of bottlenose dolphins (Tursiops truncatus) are currently known to co‐occur in the coastal waters off Virginia. A combination of visual line‐transect survey and photo‐identification (photo‐ID) methods was used to gather information on the occurrence, distribution and density of bottlenose dolphins in the coastal areas of Norfolk and Virginia Beach. Sixty‐one line‐transect surveys were completed in two zones (inshore and offshore) between August 2012 and August 2015, with on‐effort coverage of 6,550 kilometres (km) of trackline over 349.6 hours. Conventional line‐transect analysis of bottlenose dolphin sightings showed both spatial and temporal variation in density (D) and abundance (N), with highest density in the inshore zone during warm‐water months (June–November). Inshore densities were calculated as 3.51 individuals per square kilometre (km2) (N = 1,090) in the warm‐water season and 0.73 individuals/km2 (N = 225) in cool‐water months (December–May). Densities in the offshore zone were 1.24 individuals/km2 (N = 741) in the warm‐water season and 0.61 individuals/km2 (N = 366) in the cool‐water season. Warm‐water density peaks support previous research; however, this study documents a cold‐season presence of dolphins in both zones not previously reported. Twenty‐seven photo‐ID surveys were completed and a photo‐ID catalogue was created using photos taken during both dedicated photo‐ID and line‐transect surveys, containing 1,335 unique individuals. Re‐sighting numbers were low, with less than 17% of individuals documented on more than one occasion, and only 4% sighted on three or more occasions, with a maximum of 4 re‐sightings. Days between re‐sightings ranged from 5 to 970, though distance between re‐sightings spanning greater time was minimal (less than 25km). Sighting locations of photo‐IDed dolphins were broken into three regions to investigate seasonal and spatial patterns of individual distribution; dolphins sighted only in the Cape Henry (CH) or Inner Bay (IB) region were observed mostly during summer and fall seasons (93% CH, 100% IB) with none occurring during winter. For the Outer Coastline (OC) region, the majority of sightings (88%) occurred during fall and winter. Additionally, there were two individuals sighted during winter months also sighted during summer more than 130km to the north inside Chesapeake Bay (matched to a different catalogue). These sightings support the possibility that the current stock structure does not account for all dolphins in the region. Stock structure as currently understood is complicated, with overlapping spatial distribution of three stocks that separate seasonally. Our study provides information that may be useful for management, but also additional findings that could impact future stock designations

The conversion of polyolefins to monomers would create a valuable carbon feedstock from the largest fraction of waste plastic. However, breakdown of the main chains in these polymers requires the cleavage of carbon–carbon bonds that tend to resist selective chemical transformations. Here, we report the production of propylene by partial dehydrogenation of polyethylene and tandem isomerizing ethenolysis of the desaturated chain. Dehydrogenation of high-density polyethylene with either an iridium-pincer complex or platinum/zinc supported on silica as catalysts yielded dehydrogenated material containing up to 3.2% internal olefins; the combination of a second-generation Hoveyda-Grubbs metathesis catalyst and [PdP( t Bu) 3 (μ-Br)] 2 as an isomerization catalyst selectively degraded this unsaturated polymer to propylene in yields exceeding 80%. These results show promise for the application of mild catalysis to deconstruct otherwise stable polyolefins.

BACKGROUND: Dietary intake of antioxidants such as vitamins C and E protect against oxidative stress, and may also be associated with altered DNA methylation patterns. METHODS: We meta-analysed epigenome-wide association study (EWAS) results from 11,866 participants across eight population-based cohorts to evaluate the association between self-reported dietary and supplemental intake of vitamins C and E with DNA methylation. EWAS were adjusted for age, sex, BMI, caloric intake, blood cell type proportion, smoking status, alcohol consumption, and technical covariates. Significant results of the meta-analysis were subsequently evaluated in gene set enrichment analysis (GSEA) and expression quantitative trait methylation (eQTM) analysis. RESULTS: In meta-analysis, methylation at 4,656 CpG sites was significantly associated with vitamin C intake at FDR ≤ 0.05. The most significant CpG sites associated with vitamin C (at FDR ≤ 0.01) were enriched for pathways associated with systems development and cell signalling in GSEA, and were associated with downstream expression of genes enriched in the immune response in eQTM analysis. Furthermore, methylation at 160 CpG sites was significantly associated with vitamin E intake at FDR ≤ 0.05, but GSEA and eQTM analysis of the top most significant CpG sites associated with vitamin E did not identify significant enrichment of any biological pathways investigated. CONCLUSIONS: We identified significant associations of many CpG sites with vitamin C and E intake, and our results suggest that vitamin C intake may be associated with systems development and the immune response.

DNA methylation variations are prevalent in human obesity but evidence of a causative role in disease pathogenesis is limited. Here, we combine epigenome-wide association and integrative genomics to investigate the impact of adipocyte DNA methylation variations in human obesity. We discover extensive DNA methylation changes that are robustly associated with obesity (N = 190 samples, 691 loci in subcutaneous and 173 loci in visceral adipocytes, P 500 target genes, and identify putative methylation-transcription factor interactions. Through Mendelian Randomisation, we infer causal effects of methylation on obesity and obesity-induced metabolic disturbances at 59 independent loci. Targeted methylation sequencing, CRISPR-activation and gene silencing in adipocytes, further identifies regional methylation variations, underlying regulatory elements and novel cellular metabolic effects. Our results indicate DNA methylation is an important determinant of human obesity and its metabolic complications, and reveal mechanisms through which altered methylation may impact adipocyte functions.

Carbon dioxide (CO2) must be removed from the atmosphere to mitigate the negative effects of climate change. However, the most scalable methods for removing CO2 from the air require heat from fossil-fuel combustion to produce pure CO2 and continuously regenerate the sorbent. Bipolar-membrane electrodialysis (BPM-ED) is a promising technology that uses renewable electricity to dissociate water into acid and base to regenerate bicarbonate-based CO2 capture solutions, such as those used in chemical loops of direct-air-capture (DAC) processes, and also in direct-ocean capture (DOC) to promote atmospheric CO2 drawdown via decarbonization of the shallow ocean. However, a lack of understanding of the mechanisms of reactive carbon species transport in BPMs has precluded industrial-scale deployment of BPM-ED. In this study, we develop an experimentally-validated 1D model for the electrochemical regeneration of CO2 from bicarbonate-based carbon capture solutions and seawater using BPM-ED. Our experimental and computational results demonstrate that out-of-equilibrium buffer reactions within the BPM drive the formation of CO2 at the BPM/electrolyte interface with energy-intensities of less than 150 kJ mol-1. However, high rates of bubble formation increase the energy intensity of CO2 recovery at current densities >100 mA cm−2. Sensitivity analyses show that optimizing the BPM and bubble removal could enable CO2 recovery from bicarbonate solutions at energy intensities 100 mA cm−2. These results provide design principles for industrial-scale CO2 recovery using BPM-ED.

Robert K. Grasselli was a pioneer in the development and commercialization of catalysts for propene oxidation to acrolein and ammoxidation to acrylonitrile, products that today are produced at the level of over 10 billion pounds per year. The catalysts used for both processes are contain bismuth molybdates augmented by up to seven additional elements used to attain high activity, selectivity, and stability. The importance of propene oxidation and ammoxidation has stimulated considerable interest in understanding the mechanism and kinetics of these processes and the particular role of catalyst composition and structure in defining catalyst activity and selectivity. Virtually all of this work has been carried out using bismuth molybdates, primarily α-Bi2Mo3O12. The objective of this paper is to review the findings of experimental studies and illustrate how theoretical studies based on density functional theory provide additional insights that support deductions drawn from experiments and, more importantly, provide information that cannot be accessed experimentally.

Electrochemical CO2 reduction provides a promising route to the sustainable generation of valuable chemicals and fuels. Tandem catalysts enable sequential CO2-to-CO and CO-to-multicarbon (C2+) product conversions on complementary active sites, to produce high C2+ Faradaic efficiency (FE). Unfortunately, previous tandem catalysts exhibit poor management of CO intermediates, which diminishes C2+ FE. Here, we design segmented gas-diffusion electrodes (s-GDEs) in which a CO-selective catalyst layer (CL) segment at the inlet prolongs CO residence time in the subsequent C2+-selective segment, enhancing conversion. This phenomenon enables increases in both the CO utilization and C2+ current density for a Cu/Ag s-GDE compared to pure Cu, by increasing the *CO coverage within the Cu CL. Lastly, we develop a Cu/Fe-N-C s-GDE with 90% C2+ FE at C2+ partial current density (jC2+) exceeding 1 A cm−2. These results prove the importance of transport and establish design principles to improve C2+ FE and jC2+ in tandem CO2 reduction. [Figure not available: see fulltext.]

An epidemic of silicosis has emerged due to a failure to control risks associated with exposure to high-silica content respirable dust generated while working with artificial stone products. Methods for quantification of alveolar crystal burden are needed to advance our understanding of the pathobiology of silica-related lung injury as well as assisting in the diagnosis, clinical management and prognostication of affected workers. The objective of this study was to develop and validate novel methods to quantify alveolar crystal burden in bronchoalveolar lavage (BAL) fluid from patients with artificial stone silicosis.New methods to quantify and analyse alveolar crystal in BAL from patients with artificial stone silicosis were developed. Crystals were isolated and counted by microscopy and alveolar crystal burden was calculated using a standard curve generated by titration of respirable α-Quartz. The utility of the assay was then assessed in 23 patients with artificial stone silicosis.Alveolar crystal burden was greater in patients with silicosis (0.44 picograms [pg]/cell [0.08-3.49]) compared to patients with other respiratory diagnoses (0.057 pg/cell [0.01-0.34]; p 0.001). Alveolar crystal burden was positively correlated with years of silica exposure (ρ = 0.49, p = 0.02) and with decline in diffusing capacity of the lungs for carbon monoxide (ρ = -0.50, p = 0.02).Alveolar crystal burden quantification differentiates patients with silicosis from patients with other respiratory disorders. Furthermore, crystal burden is correlated with the rate of decline in lung function in patients with artificial stone silicosis.