589 research outputs found

    Variability of Internally Generated Turbulence in an Estuary, from 100 Days of Continuous Observations

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    We present detailed observations of internally generated turbulence in a sheared, stratified natural flow, as well as an analysis of the external factors leading to its generation and temporal variability. Multi-month time series of vertical profiles of velocity, acoustic backscatter (0.5 Hz), and turbulence parameters were collected with two moored acoustic Doppler current profilers (ADCPs) in the Hudson River estuary, and estuary-long transects of water density were collected 30 times. ADCP backscatter is used for visualization of coherent turbulent structures and evaluation of surface wave biases to the turbulence measurements. Benefits of the continuous long-term turbulence record include our capturing: (1) the seasonality of turbulence due to changing riverflow, (2) hysteresis in stratification and turbulence over the fortnightly cycle of tidal range, and (3) intermittent events such as breaking internal waves. Internal mixing layers (IMLs) are defined as turbulent regions above the logarithmic velocity layer, and the bottom boundary layer (BBL) is defined as the continuously turbulent range of heights above the bed. A cross-correlation analysis reveals how IML and BBL turbulence vary with stratification and external forcing from tidal range, river flow, and winds. Turbulence in both layers is maximal at spring tide and minimal when most stratified, with one exception IML turbulence at a site with changing channel depth and width is maximal at times of maximum stratification and freshwater input

    Competitive androgen receptor antagonism as a factor determining the predictability of cumulative antiandrogenic effects of widely used pesticides

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    Copyright @ 2012 National Institute of Environmental Health Sciences.This article has been made available through the Brunel Open Access Publishing Fund.Background: Many pesticides in current use have recently been revealed as in vitro androgen receptor (AR) antagonists, but information about their combined effects is lacking.
Objective: We investigated the combined effects and the competitive AR antagonism of pesticide mixtures.
Methods: We used the MDA-kb2 assay to test a combination of eight AR antagonists that did not also possess AR agonist properties (“pure” antagonists; 8 mix: fludioxonil, fenhexamid, ortho-­phenylphenol, imazalil, tebuconazole, dimetho­morph, methiocarb, pirimiphos-methyl), a combina­tion of five AR antagonists that also showed agonist activity (5 mix: cyprodinil, pyrimethanil, vinclozolin, chlor­propham, linuron), and all pesticides combined (13 mix). We used concentration addition (CA) and independent action (IA) to formu­late additivity expectations, and Schild plot analyses to investigate competitive AR antagonism.
Results: A good agreement between the effects of the mixture of eight “pure” AR antagonists and the responses predicted by CA was observed. Schild plot analysis revealed that the 8 mix acted by competi­tive AR antagonism. However, the observed responses of the 5 mix and the 13 mix fell within the “prediction window” boundaries defined by the predicted regression curves of CA and IA. Schild plot analysis with these mixtures yielded anomalous responses incompatible with competitive receptor antagonism.
Conclusions: A mixture of widely used pesticides can, in a predictable manner, produce combined AR antagonist effects that exceed the responses elicited by the most potent component alone. Inasmuch as large populations are regularly exposed to mixtures of anti­androgenic pesticides, our results underline the need for considering combination effects for these substances in regulatory practice.
This article is made available through the Brunel Open Access Publishing Fund. This work was funded by the European Commission, FP7 programme (CONTAMED, grant 212502).

    Widely Used Pesticides with Previously Unknown Endocrine Activity Revealed as in Vitro Antiandrogens

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    Background: Evidence suggests that there is widespread decline in male reproductive health and that antiandrogenic pollutants may play a significant role. There is also a clear disparity between pes¬ticide exposure and data on endocrine disruption, with most of the published literature focused on pesticides that are no longer registered for use in developed countries. Objective: We used estimated human exposure data to select pesticides to test for antiandrogenic activity, focusing on highest use pesticides. Methods: We used European databases to select 134 candidate pesticides based on highest expo-sure, followed by a filtering step according to known or predicted receptor-mediated antiandrogenic potency, based on a previously published quantitative structure–activity relationship (QSAR) model. In total, 37 pesticides were tested for in vitro androgen receptor (AR) antagonism. Of these, 14 were previously reported to be AR antagonists (“active”), 4 were predicted AR antagonists using the QSAR, 6 were predicted to not be AR antagonists (“inactive”), and 13 had unknown activity, which were “out of domain” and therefore could not be classified with the QSAR (“unknown”). Results: All 14 pesticides with previous evidence of AR antagonism were confirmed as antiandrogenic in our assay, and 9 previously untested pesticides were identified as antiandrogenic (dimethomorph, fenhexamid, quinoxyfen, cyprodinil, λ-cyhalothrin, pyrimethanil, fludioxonil, azinphos-methyl, pirimiphos-methyl). In addition, we classified 7 compounds as androgenic. Conclusions: Due to estimated antiandrogenic potency, current use, estimated exposure, and lack of previous data, we strongly recommend that dimethomorph, fludioxonil, fenhexamid, imazalil, ortho-phenylphenol, and pirimiphos-methyl be tested for antiandrogenic effects in vivo. The lack of human biomonitoring data for environmentally relevant pesticides presents a barrier to current risk assessment of pesticides on humans.European Commission (grant 21250

    Creation of functional viruses from non-functional cDNA clones obtained from an RNA virus population by the use of ancestral reconstruction

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    RNA viruses have the highest known mutation rates. Consequently it is likely that a high proportion of individual RNA virus genomes, isolated from an infected host, will contain lethal mutations and be non-functional. This is problematic if the aim is to clone and investigate high-fitness, functional cDNAs and may also pose problems for sequence-based analysis of viral evolution. To address these challenges we have performed a study of the evolution of classical swine fever virus (CSFV) using deep sequencing and analysis of 84 full-length cDNA clones, each representing individual genomes from a moderately virulent isolate. In addition to here being used as a model for RNA viruses generally, CSFV has high socioeconomic importance and remains a threat to animal welfare and pig production. We find that the majority of the investigated genomes are non-functional and only 12% produced infectious RNA transcripts. Full length sequencing of cDNA clones and deep sequencing of the parental population identified substitutions important for the observed phenotypes. The investigated cDNA clones were furthermore used as the basis for inferring the sequence of functional viruses. Since each unique clone must necessarily be the descendant of a functional ancestor, we hypothesized that it should be possible to produce functional clones by reconstructing ancestral sequences. To test this we used phylogenetic methods to infer two ancestral sequences, which were then reconstructed as cDNA clones. Viruses rescued from the reconstructed cDNAs were tested in cell culture and pigs. Both reconstructed ancestral genomes proved functional, and displayed distinct phenotypes in vitro and in vivo. We suggest that reconstruction of ancestral viruses is a useful tool for experimental and computational investigations of virulence and viral evolution. Importantly, ancestral reconstruction can be done even on the basis of a set of sequences that all correspond to non-functional variants

    Mid-Infrared Spectroscopy of Uranus from the Spitzer Infrared Spectrometer: 2. Determination of the Mean Composition of the Upper Troposphere and Stratosphere

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    Mid-infrared spectral observations Uranus acquired with the Infrared Spectrometer (IRS) on the Spitzer Space Telescope are used to determine the abundances of C2H2, C2H6, CH3C2H, C4H2, CO2, and tentatively CH3 on Uranus at the time of the 2007 equinox. For vertically uniform eddy diffusion coefficients in the range 2200-2600 cm2 s-1, photochemical models that reproduce the observed methane emission also predict C2H6 profiles that compare well with emission in the 11.6-12.5 micron wavelength region, where the nu9 band of C2H6 is prominent. Our nominal model with a uniform eddy diffusion coefficient Kzz = 2430 cm2 sec-1 and a CH4 tropopause mole fraction of 1.6x10-5 provides a good fit to other hydrocarbon emission features, such as those of C2H2 and C4H2, but the model profile for CH3C2H must be scaled by a factor of 0.43, suggesting that improvements are needed in the chemical reaction mechanism for C3Hx species. The nominal model is consistent with a CH3D/CH4 ratio of 3.0+-0.2x10-4. From the best-fit scaling of these photochemical-model profiles, we derive column abundances above the 10-mbar level of 4.5+01.1/-0.8 x 10+19 molecule-cm-2 for CH4, 6.2 +- 1.0 x 10+16 molecule-cm-2 for C2H2 (with a value 24% higher from a different longitudinal sampling), 3.1 +- 0.3 x 10+16 molecule-cm-2 for C2H6, 8.6 +- 2.6 x 10+13 molecule-cm-2 for CH3C2H, 1.8 +- 0.3 x 10+13 molecule-cm-2 for C4H2, and 1.7 +- 0.4 x 10+13 molecule-cm-2 for CO2 on Uranus. Our results have implications with respect to the influx rate of exogenic oxygen species and the production rate of stratospheric hazes on Uranus, as well as the C4H2 vapor pressure over C4H2 ice at low temperatures

    Evaluation of modelling approaches for predicting the spatial distribution of soil organic carbon stocks at the national scale

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    Soil organic carbon (SOC) plays a major role in the global carbon budget. It can act as a source or a sink of atmospheric carbon, thereby possibly influencing the course of climate change. Improving the tools that model the spatial distributions of SOC stocks at national scales is a priority, both for monitoring changes in SOC and as an input for global carbon cycles studies. In this paper, we compare and evaluate two recent and promising modelling approaches. First, we considered several increasingly complex boosted regression trees (BRT), a convenient and efficient multiple regression model from the statistical learning field. Further, we considered a robust geostatistical approach coupled to the BRT models. Testing the different approaches was performed on the dataset from the French Soil Monitoring Network, with a consistent cross-validation procedure. We showed that when a limited number of predictors were included in the BRT model, the standalone BRT predictions were significantly improved by robust geostatistical modelling of the residuals. However, when data for several SOC drivers were included, the standalone BRT model predictions were not significantly improved by geostatistical modelling. Therefore, in this latter situation, the BRT predictions might be considered adequate without the need for geostatistical modelling, provided that i) care is exercised in model fitting and validating, and ii) the dataset does not allow for modelling of local spatial autocorrelations, as is the case for many national systematic sampling schemes

    Mind the gap: Can we explain declining male reproductive health with known antiandrogens?

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    This article has been made available through the Brunel Open Access Publishing Fund.Several countries have experienced rises in cryptorchidisms, hypospadias and testicular germ cell cancer. The reasons for these trends are largely unknown, but Skakkebaek has proposed that these disorders form a testicular dysgenesis syndrome and can be traced to androgen insufficiency in foetal life. This suggests that antiandrogenic chemicals might contribute to risks, but few chemicals have been linked to these diseases in epidemiological studies. In animal studies with p,p0-dichlorodiphenyldichloroethylene, effects typical of disruptions of male sexual differentiation became apparent when the foetal levels of this androgen receptor (AR) antagonist approached values associated with responses in in vitro assays. This prompted us to analyse whether the 22 chemicals with AR antagonistic properties would produce mixture effects in an in vitro AR antagonism assay when combined at concentrations found in human serum. Other antiandrogenic modalities could not be considered. Two scenarios were investigated, one representative of average serum levels reported in European countries, the other in line with levels towards the high exposures. In both situations, the in vitro potency of the 22 selected AR antagonists was too low to produce combined AR antagonistic effects at the concentrations found in human serum, although the high exposure scenario came quite close to measurable effects. Nevertheless, our analysis exposes an explanation gap which can only be bridged by conjuring up as yet undiscovered high potency AR antagonists or, alternatively, high exposures to unknown agents of average potency

    The health impacts of women's low control in their living environment: A theory-based systematic review of observational studies in societies with profound gender discrimination.

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    We conducted a systematic review of observational evidence on the health impacts of women's low control/autonomy in the living environment in societies with profound gender discrimination and gender bias. Thirty observational studies of varying methodological quality were included. Overall, the evidence suggests that women's lower control or autonomy (for example lack of freedom of movement outside the home, lack of authority to access healthcare for sick children) was associated with poorer mental and physical health for women and higher morbidity and mortality for their children, after adjusting for their socioeconomic circumstances. Further studies are needed to disentangle and understand the pathways between low control and health outcomes in contexts of profound gender discrimination. This systematic review has highlighted the general low quality of the evidence base on this research question. It identifies the pressing need for high quality, longitudinal studies in the future
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