Visual Responses in Mice Lacking Critical Components of All Known Retinal Phototransduction Cascades

The mammalian visual system relies upon light detection by outer-retinal rod/cone photoreceptors and melanopsin-expressing retinal ganglion cells. Gnat1(-/-); Cnga3(-/-); Opn4(-/-) mice lack critical elements of each of these photoreceptive mechanisms via targeted disruption of genes encoding rod alpha transducin (Gnat1); the cone-specific alpha 3 cyclic nucleotide gated channel subunit (Cnga3); and melanopsin (Opn4). Although assumed blind, we show here that these mice retain sufficiently widespread retinal photoreception to drive a reproducible flash electroretinogram (ERG). The threshold sensitivity of this ERG is similar to that of cone-based responses, however it is lost under light adapted conditions. Its spectral efficiency is consistent with that of rod opsin, but not cone opsins or melanopsin, indicating that it originates with light absorption by the rod pigment. The TKO light response survives intravitreal injection of U73122 (a phospholipase C antagonist), but is inhibited by a missense mutation of cone alpha transducin (Gnat2(cpfl3)), suggesting Gnat2-dependence. Visual responses in TKO mice extend beyond the retina to encompass the lateral margins of the lateral geniculate nucleus and components of the visual cortex. Our data thus suggest that a Gnat1-independent phototransduction mechanism downstream of rod opsin can support relatively widespread responses in the mammalian visual system. This anomalous rod opsin-based vision should be considered in experiments relying upon Gnat1 knockout to silence rod phototransduction

Fostering learning for capability and assessing authentically: a vision for Enterprise Education

This paper explores how universities working in partnership with employers and students can design, deliver and assess a curriculum that actively encourages student engagement and helps prepare students for future multiple career pathways. After discussing a range of contextual factors impacting on employability, the authors propose an eight stage approach to developing a fit-for-purpose curriculum, with a particular focus on authentic assessment, and conclude by arguing for the necessity of an approach to curriculum design and delivery that is aligned to current and potential future graduate and employer need

Observing solar-like oscillations

We review techniques for measuring stellar oscillations in solar-type stars. Despite great efforts, no unambiguous detections have been made. A new method, based on monitoring the equivalent widths of strong lines, shows promise but is yet to be confirmed. We also discuss several subtleties, such as the need to correct for CCD non-linearities and the importance of data weighting

Acceptability of financial incentives to improve health outcomes in UK and US samples

This study was funded as part of a strategic award from the Wellcome Trust Biomedical Ethics Programme (PI Marteau: 086031/Z/08/Z)

A new method for deriving the stellar birth function of resolved stellar populations

We present a new method for deriving the stellar birth function (SBF) of resolved stellar populations. The SBF (stars born per unit mass, time, and metallicity) is the combination of the initial mass function (IMF), the star formation history (SFH), and the metallicity distribution function (MDF). The framework of our analysis is that of Poisson Point Processes (PPPs), a class of statistical models suitable when dealing with points (stars) in a multidimensional space (the measurement space of multiple photometric bands). The theory of PPPs easily accommodates the modeling of measurement errors as well as that of incompleteness. Our method avoids binning stars in the color-magnitude diagram and uses the whole likelihood function for each data point; combining the individual likelihoods allows the computation of the posterior probability for the population's SBF. Within the proposed framework it is possible to include nuisance parameters, such as distance and extinction, by specifying their prior distributions and marginalizing over them. The aim of this paper is to assess the validity of this new approach under a range of assumptions, using only simulated data. Forthcoming work will show applications to real data. Although it has a broad scope of possible applications, we have developed this method to study multi-band Hubble Space Telescope observations of the Milky Way Bulge. Therefore we will focus on simulations with characteristics similar to those of the Galactic Bulge

Efficacy of a progressive walking program and glucosamine sulphate supplementation on osteoarthritic symptoms of the hip and knee: a feasibility trial

Introduction: Management of osteoarthritis (OA) includes the use of non-pharmacological and pharmacological therapies. Although walking is commonly recommended for reducing pain and increasing physical function in people with OA, glucosamine sulphate has also been used to alleviate pain and slow the progression of OA. This study evaluated the effects of a progressive walking program and glucosamine sulphate intake on OA symptoms and physical activity participation in people with mild to moderate hip or knee OA. Methods: Thirty-six low active participants (aged 42 to 73 years) were provided with 1500 mg glucosamine sulphate per day for 6 weeks, after which they began a 12-week progressive walking program, while continuing to take glucosamine. They were randomized to walk 3 or 5 days per week and given a pedometer to monitor step counts. For both groups, step level of walking was gradually increased to 3000 steps/day during the first 6 weeks of walking, and to 6000 steps/day for the next 6 weeks. Primary outcomes included physical activity levels, physical function (self-paced step test), and the WOMAC Osteoarthritis Index for pain, stiffness and physical function. Assessments were conducted at baseline and at 6-, 12-, 18-, and 24-week follow-ups. The Mann Whitney Test was used to examine differences in outcome measures between groups at each assessment, and the Wilcoxon Signed Ranks Test was used to examine differences in outcome measures between assessments. Results: During the first 6 weeks of the study (glucosamine supplementation only), physical activity levels, physical function, and total WOMAC scores improved (P<0.05). Between the start of the walking program (Week 6) and the final follow-up (Week 24), further improvements were seen in these outcomes (P<0.05) although most improvements were seen between Weeks 6 and 12. No significant differences were found between walking groups. Conclusions: In people with hip or knee OA, walking a minimum of 3000 steps (~30 minutes), at least 3 days/week, in combination with glucosamine sulphate, may reduce OA symptoms. A more robust study with a larger sample is needed to support these preliminary findings. Trial Registration: Australian Clinical Trials Registry ACTRN012607000159459

Inverted organic photovoltaics with a solution-processed ZnO/MgO electron transport bilayer

Electron transport layers (ETLs) have been instrumental in breaking the efficiency boundaries of solution-processed photovoltaics. In particular, bilayer ETLs with an MgO top component have afforded tremendous success in various solution-processed systems, such as perovskite photovoltaics, however, their application in the promising technology of organic photovoltaics is limited. In this work, we fabricate organic photovoltaic devices incorporating a “bilayer” ZnO/MgO ETL instead of a single ZnO ETL, so as to reduce the leakage current and boost the power conversion efficiency. The ZnO/MgO ETL is shown to have a more uniform top surface and a lower work function compared to the single ZnO ETL which is expected to be beneficial to electron extraction. Furthermore, we demonstrate that insertion of the thin (≲ 10 nm) MgO interlayer in devices leads to a reduced leakage current and an increase in the shunt resistance. Application of the MgO interlayer boosts the short circuit current density and fill factor, and enhances the power conversion efficiency by ∼10% (relative increase) thereby demonstrating a facile approach to push the efficiency of organic photovoltaics to higher levels