Mixture effects at very low doses with combinations of anti-androgenic pesticides, antioxidants, industrial pollutant and chemicals used in personal care products

This article has been made available through the Brunel Open Access Publishing Fund.Many xenobiotics have been identified as in vitro androgen receptor (AR) antagonists, but information about their ability to produce combined effects at low concentrations ismissing. Such data can reveal whether joint effects at the receptor are induced at low levels andmay support the prioritisation of in vivo evaluations and provide orientations for the grouping of anti-androgens in cumulative risk assessment. Combinations of 30 AR antagonists from a wide range of sources and exposure routes (pesticides, antioxidants, parabens, UV-filters, synthetic musks, bisphenol-A, benzo(a)pyrene, perfluorooctane sulfonate and pentabromodiphenyl ether) were tested using a reporter gene assay (MDA-kb2). Chemicalswere combined at threemixture ratios, equivalent to single components' effect concentrations that inhibit the action of dihydrotesterone by 1%, 10% or 20%. Concentration addition (CA) and independent action were used to calculate additivity expectations. We observed complete suppression of dihydrotestosterone effects when chemicals were combined at individual concentrations eliciting 1%, 10% or 20% AR antagonistic effect. Due to the large number of mixture components, the combined AR antagonistic effects occurred at very low concentrations of individual mixture components. CA slightly underestimated the combined effects at all mixture ratios. In conclusion, large numbers of AR antagonists froma wide variety of sources and exposure routes have the ability of acting together at the receptor to produce joint effects at very low concentrations. Significant mixture effects are observed when chemicals are combined at concentrations that individually do not induce observable AR antagonistic effects. Cumulative risk assessment for AR antagonists should apply grouping criteria based on effects where data are available, rather than on criteria of chemical similarity

A dispersive wave pattern on Jupiter's fastest retrograde jet at 20∘20^\circS

A compact wave pattern has been identified on Jupiter's fastest retrograding jet at 20S (the SEBs) on the southern edge of the South Equatorial Belt. The wave has been identified in both reflected sunlight from amateur observations between 2010 and 2015, thermal infrared imaging from the Very Large Telescope and near infrared imaging from the Infrared Telescope Facility. The wave pattern is present when the SEB is relatively quiescent and lacking large-scale disturbances, and is particularly notable when the belt has undergone a fade (whitening). It is generally not present when the SEB exhibits its usual large-scale convective activity ('rifts'). Tracking of the wave pattern and associated white ovals on its southern edge over several epochs have permitted a measure of the dispersion relationship, showing a strong correlation between the phase speed (-43.2 to -21.2 m/s) and the longitudinal wavelength, which varied from 4.4-10.0 deg. longitude over the course of the observations. Infrared imaging sensing low pressures in the upper troposphere suggest that the wave is confined to near the cloud tops. The wave is moving westward at a phase speed slower (i.e., less negative) than the peak retrograde wind speed (-62 m/s), and is therefore moving east with respect to the SEBs jet peak. Unlike the retrograde NEBn jet near 17N, which is a location of strong vertical wind shear that sometimes hosts Rossby wave activity, the SEBs jet remains retrograde throughout the upper troposphere, suggesting the SEBs pattern cannot be interpreted as a classical Rossby wave. Cassini-derived windspeeds and temperatures reveal that the vorticity gradient is dominated by the baroclinic term and becomes negative (changes sign) in a region near the cloud-top level (400-700 mbar) associated with the SEBs, suggesting a baroclinic origin for this meandering wave pattern. [Abr]Comment: 19 pages, 11 figures, article accepted for publication in Icaru

Bioinformatics tools for analysing viral genomic data

The field of viral genomics and bioinformatics is experiencing a strong resurgence due to high-throughput sequencing (HTS) technology, which enables the rapid and cost-effective sequencing and subsequent assembly of large numbers of viral genomes. In addition, the unprecedented power of HTS technologies has enabled the analysis of intra-host viral diversity and quasispecies dynamics in relation to important biological questions on viral transmission, vaccine resistance and host jumping. HTS also enables the rapid identification of both known and potentially new viruses from field and clinical samples, thus adding new tools to the fields of viral discovery and metagenomics. Bioinformatics has been central to the rise of HTS applications because new algorithms and software tools are continually needed to process and analyse the large, complex datasets generated in this rapidly evolving area. In this paper, the authors give a brief overview of the main bioinformatics tools available for viral genomic research, with a particular emphasis on HTS technologies and their main applications. They summarise the major steps in various HTS analyses, starting with quality control of raw reads and encompassing activities ranging from consensus and de novo genome assembly to variant calling and metagenomics, as well as RNA sequencing

Maser Oscillation in a Whispering-Gallery-Mode Microwave Resonator

We report the first observation of above-threshold maser oscillation in a whispering-gallery(WG)-mode resonator, whose quasi-transverse-magnetic, 17th azimuthal-order WG mode, at a frequency of approx. 12.038 GHz, with a loaded Q of several hundred million, is supported on a cylinder of mono-crystalline sapphire. An electron spin resonance (ESR) associated with Fe3+ ions, that are substitutively included within the sapphire at a concentration of a few parts per billion, coincides in frequency with that of the (considerably narrower) WG mode. By applying a c.w. `pump' to the resonator at a frequency of approx. 31.34 GHz, with no applied d.c. magnetic field, the WG (`signal') mode is energized through a three-level maser scheme. Preliminary measurements demonstrate a frequency stability (Allan deviation) of a few times 1e-14 for sampling intervals up to 100 s.Comment: REVTeX v.4, 3 pages, with a separate .bbl file and 3 .eps figure

Barrier-controlled carrier transport in microcrystalline semiconducting materials: Description within a unified model

A recently developed model that unifies the ballistic and diffusive transport mechanisms is applied in a theoretical study of carrier transport across potential barriers at grain boundaries in microcrystalline semiconducting materials. In the unified model, the conductance depends on the detailed structure of the band edge profile and in a nonlinear way on the carrier mean free path. Equilibrium band edge profiles are calculated within the trapping model for samples made up of a linear chain of identical grains. Quantum corrections allowing for tunneling are included in the calculation of electron mobilities. The dependence of the mobilities on carrier mean free path, grain length, number of grains, and temperature is examined, and appreciable departures from the results of the thermionic-field-emission model are found. Specifically, the unified model is applied in an analysis of Hall mobility data for n-type microcrystalline Si thin films in the range of thermally activated transport. Owing mainly to the effect of tunneling, potential barrier heights derived from the data are substantially larger than the activation energies of the Hall mobilities. The specific features of the unified model, however, cannot be resolved within the rather large uncertainties of the analysis.Comment: REVTex, 19 pages, 9 figures; to appear in J. Appl. Phy

Addressing and Overcoming Barriers to E-Cigarette Use for Smoking Cessation in Pregnancy: A Qualitative Study.

E-cigarettes may have a role in supporting pregnant women who would otherwise smoke to stop smoking. The study aimed to understand pregnant women's vaping experiences, in particular how vaping to stop smoking is facilitated and how barriers to this are overcome. We conducted semi structured telephone interviews (n = 15) with pregnant or postpartum women who vaped during pregnancy, either exclusively (n = 10) or dual-used (n = 5) (smoked and vaped). Thematic analysis was used to analyse the interviews. Two themes emerged. First, 'facilitating beliefs': inherent beliefs that helped women overcome barriers to vaping. These included understanding the relative safety of vaping and economic gains compared with smoking and pregnancy being a motivator to stop smoking. Second, 'becoming a confident vaper': accumulating sufficient skill and confidence to comfortably vape. This included experimentation with e-cigarettes to ensure nicotine dependence and sensory needs were met. Seeking social support and employing strategies to address social stigma were also important. Positive beliefs about vaping and becoming proficient at vaping were viewed as ways to overcome barriers to vaping. The theoretical domain framework informed intervention recommendations to assist pregnant smokers who have tried but cannot stop smoking to switch to vaping

The Effect of Harbor Developments on Future High-Tide Flooding in Miami, Florida

Little is known about the effect of tidal changes on minor flooding in most lagoonal estuaries, often due to a paucity of historical records that predate landscape changes. In this contribution, we recover and apply archival tidal range data to show that the mean tidal range in Miami, Florida, has almost doubled since 1900, from 0.32 to 0.61 m today. A likely cause is the dredging of a ∼15 m deep, 150 m wide harbor entrance channel beginning in the early 20th century, which changed northern Biscayne Bay from a choked inlet system to one with a tidal range close to coastal conditions. To investigate the implications for high-tide flooding, we develop and validate a tidal-inference based methodology that leverages estimates of pre-1900 tidal range to obtain historical tidal predictions and constituents. Next, water level predictions that represent historical and modern water level variations are projected forward in time using different sea level rise scenarios. Results show that the historical increase in tidal range hastened the occurrence of present-day flooding, and that the total integrated number of days with high-tide floods in the 2020–2100 period will be approximately O(103) more under present day tides compared to pre-development conditions. These results suggest that tidal change may be a previously under-appreciated factor in the increasing prevalence of high-tide flooding in lagoonal estuaries, and our methods open the door to improving our understanding of other heavily-altered systems

Group-based microfinance for collective empowerment: a systematic review of health impacts

$\textbf{Objective}$ To assess the impact on health-related outcomes, of group microfinance schemes based on collective empowerment. $\textbf{Methods}$ We searched the databases Social Sciences Citation Index, Embase, MEDLINE, MEDLINE In-Process, PsycINFO, Social Policy & Practice and Conference Proceedings Citation Index for articles published between 1 January 1980 and 29 February 2016. Articles reporting on health impacts associated with group-based microfinance were included in a narrative synthesis. $\textbf{Findings}$ We identified one cluster-randomized control trial and 22 quasi-experimental studies. All of the included interventions targeted poor women living in low- or middle-income countries. Some included a health-promotion component. The results of the higher quality studies indicated an association between membership of a microfinance scheme and improvements in the health of women and their children. The observed improvements included reduced maternal and infant mortality, better sexual health and, in some cases, lower levels of interpersonal violence. According to the results of the few studies in which changes in empowerment were measured, membership of the relatively large and well-established microfinance schemes generally led to increased empowerment but this did not necessarily translate into improved health outcomes. Qualitative evidence suggested that increased empowerment may have contributed to observed improvements in contraceptive use and mental well-being and reductions in the risk of violence from an intimate partner. $\textbf{Conclusion}$ Membership of the larger, well-established group-based microfinance schemes is associated with improvements in some health outcomes. Future studies need to be designed to cope better with bias and to assess negative as well as positive social and health impacts.The systematic review was funded by the United Kingdom Department of Health through the Public Health Research Consortium

Computational modelling of cancerous mutations in the EGFR/ERK signalling pathway

This article has been made available through the Brunel Open Access Publishing Fund - Copyright @ 2009 Orton et al.BACKGROUND: The Epidermal Growth Factor Receptor (EGFR) activated Extracellular-signal Regulated Kinase (ERK) pathway is a critical cell signalling pathway that relays the signal for a cell to proliferate from the plasma membrane to the nucleus. Deregulation of the EGFR/ERK pathway due to alterations affecting the expression or function of a number of pathway components has long been associated with numerous forms of cancer. Under normal conditions, Epidermal Growth Factor (EGF) stimulates a rapid but transient activation of ERK as the signal is rapidly shutdown. Whereas, under cancerous mutation conditions the ERK signal cannot be shutdown and is sustained resulting in the constitutive activation of ERK and continual cell proliferation. In this study, we have used computational modelling techniques to investigate what effects various cancerous alterations have on the signalling flow through the ERK pathway. RESULTS: We have generated a new model of the EGFR activated ERK pathway, which was verified by our own experimental data. We then altered our model to represent various cancerous situations such as Ras, B-Raf and EGFR mutations, as well as EGFR overexpression. Analysis of the models showed that different cancerous situations resulted in different signalling patterns through the ERK pathway, especially when compared to the normal EGF signal pattern. Our model predicts that cancerous EGFR mutation and overexpression signals almost exclusively via the Rap1 pathway, predicting that this pathway is the best target for drugs. Furthermore, our model also highlights the importance of receptor degradation in normal and cancerous EGFR signalling, and suggests that receptor degradation is a key difference between the signalling from the EGF and Nerve Growth Factor (NGF) receptors. CONCLUSION: Our results suggest that different routes to ERK activation are being utilised in different cancerous situations which therefore has interesting implications for drug selection strategies. We also conducted a comparison of the critical differences between signalling from different growth factor receptors (namely EGFR, mutated EGFR, NGF, and Insulin) with our results suggesting the difference between the systems are large scale and can be attributed to the presence/absence of entire pathways rather than subtle difference in individual rate constants between the systems.This work was funded by the Department of Trade and Industry (DTI), under their Bioscience Beacon project programme. AG was funded by an industrial PhD studentship from Scottish Enterprise and Cyclacel

EVOLUTION OF THE STRATOSPHERIC TEMPERATURE AND CHEMICAL COMPOSITION OVER ONE TITANIAN YEAR

Since the Voyager 1 (V1) flyby in 1980, Titans exploration from space and the ground has been ongoing for more than a full revolution of Saturn around the Sun (one Titan year or 29.5 Earth years was completed in May 2010). In this study we search for temporal variations affecting Titans atmospheric thermal and chemical structure within that year. We process Cassini CIRS data taken during the Titan flybys from 2006-2013 and compare them to the 1980 V1IRIS spectra (re-analyzed here). We also consider data from Earth-based and -orbiting observatories (such as from the ISO, re-visited). When we compare the CIRS 2010 and the IRIS data we find limited inter-annual variations, below the 25 or35 levels for the lower and middle, or the high latitudes, respectively. A return to the 1980 stratospheric temperatures and abundances is generally achieved from 50degN to 50degS, indicative of the solar radiation being the dominating energy source at 10 AU, as for the Earth, as predicted by GCM and photochemical models. However, some exceptions exist among the most complex hydrocarbons (C4H2 and C3H4), especially in the North. In the Southern latitudes, since 2012, we see a trend for an increase of several trace gases, possibly indicative of a seasonal atmospheric reversal. At the Northern latitudes we found enhanced abundances around the period of the northern spring equinox in mid-2009 (as in Bampasidis et al. 2012), which subsequently decreased (from 2010-2012) returning to values similar to those found in the V1 epoch a Titanian year before