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Retinal function beyond foveal vision is not routinely examined in the clinical screening and management of diabetic retinopathy although growing evidence suggests it may precede structural changes. In this study we compare optical coherence tomography (OCT) based macular structure with function measured objectively with the ObjectiveFIELD Analyzer (OFA), and with Matrix perimetry. We did that longitudinally in Type 2 diabetes (T2D) patients with mild Diabetic Macular Oedema (DMO) with good vision and a similar number of T2D patients without DMO, to evaluate changes in retinal function more peripherally over the natural course of retinopathy. Both eyes of 16 T2D patients (65.0 ± 10.1, 10 females), 10 with baseline DMO, were followed for up longitudinally for 27 months providing 94 data sets. Vasculopathy was assessed by fundus photography. Retinopathy was graded using to Early Treatment of Diabetic Retinopathy Study (ETDRS) guidelines. Posterior-pole OCT quantified a 64-region/eye thickness grid. Retinal function was measured with 10-2 Matrix perimetry, and the FDA-cleared OFA. Two multifocal pupillographic objective perimetry (mfPOP) variants presented 44 stimuli/eye within either the central 30° or 60° of the visual field, providing sensitivities and delays for each test-region. OCT, Matrix and 30° OFA data were mapped to a common 44 region/eye grid allowing change over time to be compared at the same retinal regions. In eyes that presented with DMO at baseline, mean retinal thickness reduced from 237 ± 25 μm to 234.2 ± 26.7 μm, while the initially non-DMO eyes significantly increased their mean thickness from 250.7 ± 24.4 μm to 255.7 ± 20.6 μm (both p<0.05). Eyes that reduced in retinal thickness over time recovered to more normal OFA sensitivities and delays (all p<0.021). Matrix perimetry quantified fewer regions that changed significantly over the 27 months, mostly presenting in the central 8 degrees. Changes in retinal function measured by OFA possibly offer greater power to monitor DMO over time than Matrix perimetry data.

Compressive sensing is a simultaneous data acquisition and compression technique, which can significantly reduce data bandwidth, data storage volume, and power. We apply this technique for transient photometric events. In this work, we analyze the effect of noise on the detection of these events using compressive sensing (CS). We show numerical results on the impact of source and measurement noise on the reconstruction of transient photometric curves, generated due to gravitational microlensing events. In our work, we define source noise as background noise, or any inherent noise present in the sampling region of interest. For our models, measurement noise is defined as the noise present during data acquisition. These results can be generalized for any transient photometric CS measurements with source noise and CS data acquisition measurement noise. Our results show that the CS measurement matrix properties have an effect on CS reconstruction in the presence of source noise and measurement noise. We provide potential solutions for improving the performance by tuning some of the properties of the measurement matrices. For source noise applications, we show that choosing a measurement matrix with low mutual coherence can lower the amount of error caused due to CS reconstruction. Similarly, for measurement noise addition, we show that by choosing a lower expected value of the binomial measurement matrix, we can lower the amount of error due to CS reconstruction.

'The International Handbook of Public Financial Management' is essential reading for governmental policy-makers, and practitioners and consultants working in this field, whose importance has been highlighted by the global financial crisis. It is a primary source for academics and students of economics, public finance, accountancy and public policy.

The essential process of protein secretion is achieved by the ubiquitous Sec machinery. In prokaryotes, the drive for translocation comes from ATP hydrolysis by the cytosolic motor-protein SecA, in concert with the proton motive force (PMF). However, the mechanism through which ATP hydrolysis by SecA is coupled to directional movement through SecYEG is unclear. Here, we combine all-atom molecular dynamics (MD) simulations with single molecule FRET and biochemical assays. We show that ATP binding by SecA causes opening of the SecY-channel at long range, while substrates at the SecY-channel entrance feed back to regulate nucleotide exchange by SecA. This two-way communication suggests a new, unifying 'Brownian ratchet' mechanism, whereby ATP binding and hydrolysis bias the direction of polypeptide diffusion. The model represents a solution to the problem of transporting inherently variable substrates such as polypeptides, and may underlie mechanisms of other motors that translocate proteins and nucleic acids. A protective membrane surrounds all cells, and controls what goes in and out of the cell. Many proteins that are made inside the cell need to be exported in order to do their job. In most organisms, a specialised transport motor that sits inside the membrane, known as 'Sec', carries out this export process. Sec recognises proteins that need to be exported and pushes them across the membrane and out of the cell. The energy required to do this comes from the cell's universal power source, a molecule called ATP. Previous studies have shown what Sec looks like, but not how it pushes proteins from one side of the membrane to the other. Currently, the most popular theory for how Sec works is that it grabs hold of part of the protein and pushes it through a gate in the membrane. It then lets go and goes back to grab and push the next bit of the protein. Allen, Corey, Oatley et al. have now used a combination of experimental and computational methods to look at how the different parts of Sec move around as it uses ATP. The reasoning behind using these methods was that it's easier to understand how a motor works by watching it in action rather than just looking at a still picture. Using these methods, Allen, Corey, Oatley et al. show that the biggest movement in Sec as it uses ATP is in the membrane gate itself, which opens and closes. This suggests that Sec acts like a turnstile: proteins can freely move one way across the membrane, but are prevented from moving back in again. This mechanism has not been described before and may apply to other transport systems. Further investigations will be needed to understand exactly how Sec recognises cargo and starts the transport process, and to explore the specific features of a protein that activate the turnstile. It also remains to be discovered how this transport process differs in other, non-bacterial cells. This could potentially help us develop new drugs that specifically block the bacterial Sec system without affecting human cells.

In this work, we provide a compressive sensing architecture for implementing on a space based observatory for detecting transient photometric parallax caused by gravitational microlensing events. Compressive sensing (CS) is a simultaneous data acquisition and compression technique, which can greatly reduce on-board resources required for space flight data storage and ground transmission. We simulate microlensing parallax observations using a space observatory constellation, based on CS detectors. Our results show that average CS error is less than 0.5% using 25% Nyquist rate samples. The error at peak magnification time is significantly lower than the error for distinguishing any two microlensing parallax curves at their peak magnification. Thus, CS is an enabling technology for detecting microlensing parallax, without causing any loss in detection accuracy.

Purpose To compare diagnostic power for different severities of age-related macular degeneration (AMD) of two-dimensional macular pigment optical densities (2D-MPOD) and spatially matched objective perimetry, with standard perimetry and best-corrected visual acuity (BCVA). Methods The ObjectiveField Analyser (OFA) provided objective perimetry, and a Heidelberg Spectralis optical coherence tomography (OCT) measured 2D-MPOD in AMD patients, both completed twice over 0.99 ± 0.16 years. From each 2D-MPOD image, we extracted 20 regions/macula, matched to the 20 OFA stimuli/macula. For each region, we calculated 7 measures from the 2D-MPOD pixel values and correlated those with OFA sensitivities and delays. We quantified 2D-MPOD changes, the ability of 2D-MPOD and OFA to discriminate AMD stages, and the discriminatory power of Matrix perimetry and BCVA using percentage area under receiver operator characteristic plots (%AUROC). Results In 58 eyes of 29 subjects (71.6 ± 6.3 years, 22 females), we found significant correlations between 2D-MPOD and OFA sensitivities for Age-Related Eye Disease Studies (AREDS)-3 and AREDS-4 severities. Delays showed significant correlations with AREDS-2. For AREDS-4, correlations extended across all eccentricities. Regression associated with the Bland–Altman plots showed significant changes in 2D-MPOD over the study period, especially variability measures . MPOD per-region medians discriminated AREDS-1 from AREDS-3 eyes at a %AUROC of 80.0 ± 6.3%, outperforming OFA, Matrix perimetry, and BCVA. Conclusions MPOD changes correlated with central functional changes and significant correlations extended peripherally in later-stage AMD. Good diagnostic power for earlier-stage AMD and significant change over the study suggest that 2D-MPOD and OFA may provide effective biomarkers.