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Extensive wave measurements were collected on the North Carolina-Virginia continental shelf in the autumn of 1999. Comparisons of observations and spectral refraction computations reveal strong cross-shelf decay of energetic remotely generated swell with, for one particular event, a maximum reduction in wave energy of 93% near the Virginia coastline, where the shelf is widest. These dramatic energy losses were observed in light-wind conditions when dissipation in the surface boundary layer caused by wave breaking (whitecaps) was weak and wave propagation directions were onshore with little directional spreading. These observations suggest that strong dissipation of wave energy takes place in the bottom boundary layer. The inferred dissipation is weaker for smaller-amplitude swells. For the three swell events described here, observations are reproduced well by numerical model hindcasts using a parameterization of wave friction over a movable sandy bed. Directional spectra that are narrow off the shelf are observed to broaden significantly as waves propagate over the inner shelf, although refraction theory predicts a narrowing. This broadening generally agrees with predictions of Bragg scattering of random waves by the irregular seafloor topography. [PUBLICATION ABSTRACT]

Surface-following buoys are widely used to collect routine ocean wave measurements. While accelerometer and tilt sensors have been used for decades to measure the wave-induced buoy displacements, alternative global positioning system (GPS) sensor packages have been introduced recently that are generally smaller, less expensive, and do not require calibration. In this study, the capabilities of several GPS sensors are evaluated with field observations in wind-sea and swell conditions off the California coast. The GPS buoys used in this study include Datawell Directional Waverider and Mini Directional Waverider buoys equipped with a specialized GPS Doppler shift sensor, and a low-cost experimental drifter equipped with an “off the shelf” GPS receiver for absolute position tracking. Various GPS position receivers were attached to the Waverider buoys to evaluate their potential use in low-cost wave-resolving drifters. Intercomparisons between the Datawell GPS-based buoys, the experimental GPS drifter, and a conventional Datawell buoy with an accelerometer–tilt–compass sensor package, show good agreement in estimates of wave frequency and direction spectra. Despite the limited (several meters) absolute accuracy of the GPS position receivers, the horizontal wave orbital displacements are accurately resolved, even in benign (significant wave height less than 1 m) swell conditions. Vertical sea surface displacements were not well resolved by the GPS position receivers with built-in or small patch antennas, but accurately measured when an external precision antenna was attached to the drifter. Overall, the field tests show excellent agreement between Datawell buoys using GPS and motion-sensor packages, and demonstrate the feasibility of observing ocean surface waves with low-cost GPS-tracked drifters.

State-of-the-art parameterizations of the interactions of waves with a sandy bottom are evaluated using extensive field observations of swell evolution across the North Carolina continental shelf and hindcasts performed with the spectral wave prediction model CREST. The spectral energy balance equation, including bottom friction and wave-bottom scattering source terms, was integrated numerically for selected time periods with swell-dominated conditions. Incident wave spectra at the model boundary were estimated from buoy measurements near the shelf break, assuming weak spatial variations in the offshore wave field. The observed strong and variable decay of the significant wave height across the shelf is predicted accurately with an overall scatter index of 0.15. Predicted wave directional properties at the peak frequency also agree well with observations, with a 5[degrees] root-mean-square error on the mean direction at the peak frequency and a 0.22 scatter index for the directional spread. Slight modifications are proposed for the laboratory-based empirical constants in the movable bed bottom friction source term, reducing the wave height scatter index to 0.13. A significant negative bias in the predicted directional spread (about -20%) suggests that other wave scattering processes not included in the energy balance equation broaden the wave field near the shore. Other residual errors may be largely the result of neglected spatial variations in the offshore wave conditions and, to a lesser extent, insufficient knowledge of the sediment properties. [PUBLICATION ABSTRACT]

State-of-the-art parameterizations of the interactions of waves with a sandy bottom are evaluated using extensive field observations of swell evolution across the North Carolina continental shelf and hindcasts performed with the spectral wave prediction model CREST. The spectral energy balance equation, including bottom friction and wave-bottom scattering source terms, was integrated numerically for selected time periods with swell-dominated conditions. Incident wave spectra at the model boundary were estimated from buoy measurements near the shelf break, assuming weak spatial variations in the offshore wave field. The observed strong and variable decay of the significant wave height across the shelf is predicted accurately with an overall scatter index of 0.15. Predicted wave directional properties at the peak frequency also agree well with observations, with a 5 degree root-mean-square error on the mean direction at the peak frequency and a 0.22 scatter index for the directional spread. Slight modifications are proposed for the laboratory-based empirical constants in the movable bed bottom friction source term, reducing the wave height scatter index to 0.13. A significant negative bias in the predicted directional spread (about -20%) suggests that other wave scattering processes not included in the energy balance equation broaden the wave field near the shore. Other residual errors may be largely the result of neglected spatial variations in the offshore wave conditions and, to a lesser extent, insufficient knowledge of the sediment properties.

Extensive wave measurements were collected on the North Carolina-Virginia continental shelf in the autumn of 1999. Comparisons of observations and spectral refraction computations reveal strong cross-shelf decay of energetic remotely generated swell with, for one particular event, a maximum reduction in wave energy of 93% near the Virginia coastline, where the shelf is widest. These dramatic energy losses were observed in light-wind conditions when dissipation in the surface boundary layer caused by wave breaking (whitecaps) was weak and wave propagation directions were onshore with little directional spreading. These observations suggest that strong dissipation of wave energy takes place in the bottom boundary layer. The inferred dissipation is weaker for smaller-amplitude swells. For the three swell events described here, observations are reproduced well by numerical model hindcasts using a parameterization of wave friction over a movable sandy bed. Directional spectra that are narrow off the shelf are observed to broaden significantly as waves propagate over the inner shelf, although refraction theory predicts a narrowing. This broadening generally agrees with predictions of Bragg scattering of random waves by the irregular seafloor topography.

Background The environmental presence of airborne micro- and nanoplastics (MNPs) raises concerns about their impact on the development and progression of respiratory diseases, including chronic obstructive pulmonary disease (COPD). In this study, we investigated the potential toxicity of amorphous, environmentally relevant MNPs in primary bronchial epithelial cells (PBEC) exposed at the air-liquid interface (ALI). Methods Differentiated PBEC cultures from COPD donors ( n  = 3) and non-COPD donors ( n  = 3) were exposed for 24 h to polyvinylchloride (PVC), polypropylene (PP), or polyamide-6,6 (PA) MNPs (> 75% of particles < 1 μm) via small droplet application. Cytotoxicity, inflammation, cellular composition, morphology and integrity of the epithelial barrier as well as antioxidant and autophagy-related processes were assessed by a combination of lactate dehydrogenase leakage, IL-8 secretion, transmission electron microscopy and gene expression analyses. Results All PBEC cultures formed an intact epithelial barrier. However, transepithelial electrical resistance (TEER) and transcript levels of tight junction protein Claudin 4 were lower (FC = 0.36, p  = 0.02) in COPD-PBEC versus non-COPD PBEC. Although with some inter-donor variability, MNPs did not induce profound cytotoxicity or inflammation. However, PA MNPs (3 µg/cm 2 ), decreased expression of Zonula Occludens-1 (FC = 0.76, p  = 0.01), Occludin (FC = 0.75, p  = 0.03) and modulated cell-type specific genes in COPD-PBEC, suggesting (early) epithelial barrier disruption. Additionally, differential regulation of transcript levels of antioxidant, apoptotic and autophagy genes was observed between COPD and non-COPD in response to PVC and PA. Conclusion These results indicate that MNP exposure, especially PA, can induce (sub)toxic effects in PBEC, with substantial inter-donor variability. Whether this impacts COPD development remains to be studied.

Obesity, diabetes, hypertension, and hyperlipidemia constitute risk factors for morbidity and premature mortality. Based on animal and in vitro studies, resveratrol reverts these risk factors via stimulation of silent mating type information regulation 2 homolog 1 (SIRT1), but data in human subjects are scarce. The objective of this study was to examine the metabolic effects of high-dose resveratrol in obese human subjects. In a randomized, placebo-controlled, double-blinded, and parallel-group design, 24 obese but otherwise healthy men were randomly assigned to 4 weeks of resveratrol or placebo treatment. Extensive metabolic examinations including assessment of glucose turnover and insulin sensitivity (hyperinsulinemic euglycemic clamp) were performed before and after the treatment. Insulin sensitivity, the primary outcome measure, deteriorated insignificantly in both groups. Endogenous glucose production and the turnover and oxidation rates of glucose remained unchanged. Resveratrol supplementation also had no effect on blood pressure; resting energy expenditure; oxidation rates of lipid; ectopic or visceral fat content; or inflammatory and metabolic biomarkers. The lack of effect disagrees with persuasive data obtained from rodent models and raises doubt about the justification of resveratrol as a human nutritional supplement in metabolic disorders.

The global genetic diversity of cassava and related Manihot species is revealed by sequencing of 53 cultivated and wild accessions and genotyping of 268 African cassavas, providing a vital resource for breeding. Cassava ( Manihot esculenta ) provides calories and nutrition for more than half a billion people. It was domesticated by native Amazonian peoples through cultivation of the wild progenitor M. esculenta ssp. flabellifolia and is now grown in tropical regions worldwide. Here we provide a high-quality genome assembly for cassava with improved contiguity, linkage, and completeness; almost 97% of genes are anchored to chromosomes. We find that paleotetraploidy in cassava is shared with the related rubber tree Hevea , providing a resource for comparative studies. We also sequence a global collection of 58 Manihot accessions, including cultivated and wild cassava accessions and related species such as Ceará or India rubber ( M. glaziovii ), and genotype 268 African cassava varieties. We find widespread interspecific admixture, and detect the genetic signature of past cassava breeding programs. As a clonally propagated crop, cassava is especially vulnerable to pathogens and abiotic stresses. This genomic resource will inform future genome-enabled breeding efforts to improve this staple crop.

Tenofovir alafenamide shows high antiviral efficacy and improved renal and bone safety compared with tenofovir disoproxil fumarate when used for HIV treatment. Here, we report primary results from a blinded phase 3 study evaluating the efficacy and safety of pre-exposure prophylaxis (PrEP) with emtricitabine and tenofovir alafenamide versus emtricitabine and tenofovir disoproxil fumarate for HIV prevention. This study is an ongoing, randomised, double-blind, multicentre, active-controlled, phase 3, non-inferiority trial done at 94 community, public health, and hospital-associated clinics located in regions of Europe and North America, where there is a high incidence of HIV or prevalence of people living with HIV, or both. We enrolled adult cisgender men who have sex with men and transgender women who have sex with men, both with a high risk of acquiring HIV on the basis of their self-reported sexual behaviour in the past 12 weeks or their recent history (within 24 weeks of enrolment) of bacterial sexually transmitted infections. Participants with current or previous use of PrEP with emtricitabine and tenofovir disoproxil fumarate were not excluded. We used a computer-generated random allocation sequence to randomly assign (1:1) participants to receive either emtricitabine (200 mg) and tenofovir alafenamide (25 mg) tablets daily, with matched placebo tablets (emtricitabine and tenofovir alafenamide group), or emtricitabine (200 mg) and tenofovir disoproxil fumarate (300 mg) tablets daily, with matched placebo tablets (emtricitabine and tenofovir disoproxil fumarate group). As such, all participants were given two tablets. The trial sponsor, investigators, participants, and the study staff who provided the study drugs, assessed the outcomes, and collected the data were masked to group assignment. The primary efficacy outcome was incident HIV infection, which was assessed when all participants had completed 48 weeks of follow-up and half of all participants had completed 96 weeks of follow-up. This full analysis set included all randomly assigned participants who had received at least one dose of the assigned study drug and had at least one post-baseline HIV test. Non-inferiority of emtricitabine and tenofovir alafenamide to emtricitabine and tenofovir disoproxil fumarate was established if the upper bound of the 95·003% CI of the HIV incidence rate ratio (IRR) was less than the prespecified non-inferiority margin of 1·62. We prespecified six secondary bone mineral density and renal biomarker safety endpoints to evaluate using the safety analysis set. This analysis set included all randomly assigned participants who had received at least one dose of the assigned study drug. This trial is registered with ClinicalTrials.gov, NCT02842086, and is no longer recruiting. Between Sept 13, 2016, and June 30, 2017, 5387 (92%) of 5857 participants were randomly assigned and received emtricitabine and tenofovir alafenamide (n=2694) or emtricitabine and tenofovir disoproxil fumarate (n=2693). At the time of the primary efficacy analysis (ie, when all participants had completed 48 weeks and 50% had completed 96 weeks) emtricitabine and tenofovir alafenamide was non-inferior to emtricitabine and tenofovir disoproxil fumarate for HIV prevention, as the upper limit of the 95% CI of the IRR, was less than the prespecified non-inferiority margin of 1·62 (IRR 0·47 [95% CI 0·19–1·15]). After 8756 person-years of follow-up, 22 participants were diagnosed with HIV, seven participants in the emtricitabine and tenofovir alafenamide group (0·16 infections per 100 person-years [95% CI 0·06–0·33]), and 15 participants in the emtricitabine and tenofovir disoproxil fumarate group (0·34 infections per 100 person-years [0·19–0·56]). Both regimens were well tolerated, with a low number of participants reporting adverse events that led to discontinuation of the study drug (36 [1%] of 2694 participants in the emtricitabine and tenofovir alafenamide group vs 49 [2%] of 2693 participants in the emtricitabine and tenofovir disoproxil fumarate group). Emtricitabine and tenofovir alafenamide was superior to emtricitabine and tenofovir disoproxil fumarate in all six prespecified bone mineral density and renal biomarker safety endpoints. Daily emtricitabine and tenofovir alafenamide shows non-inferior efficacy to daily emtricitabine and tenofovir disoproxil fumarate for HIV prevention, and the number of adverse events for both regimens was low. Emtricitabine and tenofovir alafenamide had more favourable effects on bone mineral density and biomarkers of renal safety than emtricitabine and tenofovir disoproxil fumarate. Gilead Sciences.

Inorganic polyphosphate is a ubiquitous, linear biopolymer built of up to thousands of phosphate residues that are linked by energy-rich phosphoanhydride bonds. Polyphosphate kinases of the family 2 (PPK2) use polyphosphate to catalyze the reversible phosphorylation of nucleotide phosphates and are highly relevant as targets for new pharmaceutical compounds and as biocatalysts for cofactor regeneration. PPK2s can be classified based on their preference for nucleoside mono- or diphosphates or both. The detailedmechanism of PPK2s and the molecular basis for their substrate preference is unclear, which is mainly due to the lack of high-resolution structures with substrates or substrate analogs. Here, we report the structural analysis and comparison of a class I PPK2 (ADP-phosphorylating) and a class III PPK2 (AMP- and ADP-phosphorylating), both complexed with polyphosphate and/or nucleotide substrates. Together with complementary biochemical analyses, these define the molecular basis of nucleotide specificity and are consistent with a Mg2+ catalyzed in-line phosphoryl transfer mechanism. This mechanistic insight will guide the development of PPK2 inhibitors as potential antibacterials or genetically modified PPK2s that phosphorylate alternative substrates.