Identification of molecular markers of delayed graft function based on the regulation of biological ageing

Introduction: Delayed graft function is a prevalent clinical problem in renal transplantation for which there is no objective system to predict occurrence in advance. It can result in a significant increase in the necessity for hospitalisation post-transplant and is a significant risk factor for other post-transplant complications. Methodology: The importance of microRNAs (miRNAs), a specific subclass of small RNA, have been clearly demonstrated to influence many pathways in health and disease. To investigate the influence of miRNAs on renal allograft performance post-transplant, the expression of a panel of miRNAs in pre-transplant renal biopsies was measured using qPCR. Expression was then related to clinical parameters and outcomes in two independent renal transplant cohorts. Results: Here we demonstrate, in two independent cohorts of pre-implantation human renal allograft biopsies, that a novel pre-transplant renal performance scoring system (GRPSS), can determine the occurrence of DGF with a high sensitivity (>90%) and specificity (>60%) for donor allografts pre-transplant, using just three senescence associated microRNAs combined with donor age and type of organ donation. Conclusion: These results demonstrate a relationship between pre-transplant microRNA expression levels, cellular biological ageing pathways and clinical outcomes for renal transplantation. They provide for a simple, rapid quantitative molecular pre-transplant assay to determine post-transplant allograft function and scope for future intervention. Furthermore, these results demonstrate the involvement of senescence pathways in ischaemic injury during the organ transplantation process and an indication of accelerated bio-ageing as a consequence of both warm and cold ischaemia

MSG Instant Messenger: Social Presence and Location for the "Ad Hoc Learning Experience"

"Elearning2.0" promises to harness the power of three of today's most disruptive technologies: social software, elearning, and Web2.0. Our own work in this disruptive space takes as a starting premise that social networking is critical for learning: finding the right person can be more important than 'scouring the web for an answer', particularly when hand-holding or other explanatory services are required. Moreover, it 'feels good' to know that others are around! With this in mind, we have taken our older BuddySpace tool, and created a new tool we call MSG, which is simpler, available as Open Source, and integrates cleanly with a number of other services, including Moodle and Google Maps.Editor: Patrick McAndrew (Open University, UK).Reviewers: Robert Schuwer (Open University, NL) and Patrick McAndrew (Open University, UK)

From Classical Four-Wave Mixing to Parametric Fluorescence in Silicon micro-ring resonators

Four-wave mixing can be stimulated or occur spontaneously. The first process is intrinsically much stronger, and well understood through classical nonlinear optics. The latter, also known as parametric fluorescence, can be explained only in the framework of a quantum theory of light. We experimentally demonstrate that, in a micro-ring resonator, there exists a simple relation between the efficiencies of these two processes, which is independent of the nonlinearity and size of the ring. In particular we show that the average power generated by parametric fluorescence can be immediately estimated from a classical FWM experiment. These results suggest that classical nonlinear characterization of a photonic integrated structure can provide accurate information on its nonlinear quantum properties.Comment: 4 pages, 3 figure

Computational modelling of solvent effects in a prolific solvatomorphic porous organic cage

Crystal structure prediction methods can enable the in silico design of functional molecular crystals, but solvent effects can have a major influence on relative lattice energies sometimes thwarting predictions. This is particularly true for porous solids, where solvent included in the pores can have an important energetic contribution. Here we present a Monte Carlo solvent insertion procedure for predicting the solvent filling of porous structures from crystal structure prediction landscapes, tested using a highly solvatomorphic porous organic cage molecule, CC1. We use this method to rationalise the fact that the predicted global energy minimum structure for CC1 is never observed from solvent crystallisation. We also explain the formation of three different solvatomorphs of CC1 from three structurally-similar chlorinated solvents. Calculated solvent stabilisation energies are found to correlate with experimental results from thermogravimetric analysis, suggesting a future computational framework for a priori materials design that includes solvation effects

Mining predicted crystal structure landscapes with high throughput crystallisation: old molecules, new insights

Organic molecules tend to close pack to form dense structures when they are crystallized from organic solvents. Porous molecular crystals defy this rule: they typically crystallize with lattice solvent in the interconnected pores. However, the design and discovery of such structures is often challenging and time consuming, in part because it is difficult to predict solvent effects on crystallization. Here, we combine crystal structure prediction (CSP) with a high-throughput crystallization screening method to accelerate the discovery of stable hydrogen-bonded frameworks. We exemplify this strategy by finding new phases of two well-studied molecules in a computationally targeted way. Specifically, we find a new porous polymorph of trimesic acid, δ-TMA, that has a guest free hexagonal pore structure, as well as three new solvent-stabilized diamondoid frameworks of adamantane-1,3,5,7-tetracarboxylic acid (ADTA)

The DEEP2 Galaxy Redshift Survey: The Evolution of Void Statistics from z~1 to z~0

We present measurements of the void probability function (VPF) at z~1 using data from the DEEP2 Redshift Survey and its evolution to z~0 using data from the Sloan Digital Sky Survey (SDSS). We measure the VPF as a function of galaxy color and luminosity in both surveys and find that it mimics trends displayed in the two-point correlation function, $\xi$; namely that samples of brighter, red galaxies have larger voids (i.e. are more strongly clustered) than fainter, blue galaxies. We also clearly detect evolution in the VPF with cosmic time, with voids being larger in comoving units at z~0. We find that the reduced VPF matches the predictions of a `negative binomial' model for galaxies of all colors, luminosities, and redshifts studied. This model lacks a physical motivation, but produces a simple analytic prediction for sources of any number density and integrated two-point correlation function, \bar{\xi}. This implies that differences in the VPF across different galaxy populations are consistent with being due entirely to differences in the population number density and \bar{\xi}. The robust result that all galaxy populations follow the negative binomial model appears to be due to primarily to the clustering of dark matter halos. The reduced VPF is insensitive to changes in the parameters of the halo occupation distribution, in the sense that halo models with the same \bar{\xi} will produce the same VPF. For the wide range of galaxies studied, the VPF therefore does not appear to provide useful constraints on galaxy evolution models that cannot be gleaned from studies of \bar{\xi} alone. (abridged)Comment: 17 pages, 15 figures, ApJ accepte

Porous organic cages for sulfur hexafluoride separation

A series of porous organic cages is examined for the selective adsorption of sulfur hexafluoride (SF6) over nitrogen. Despite lacking any metal sites, a porous cage, CC3, shows the highest SF6/N2 selectivity reported for any material at ambient temperature and pressure, which translates to real separations in a gas breakthrough column. The SF6 uptake of these materials is considerably higher than would be expected from the static pore structures. The location of SF6 within these materials is elucidated by X-ray crystallography, and it is shown that cooperative diffusion and structural rearrangements in these molecular crystals can rationalize their superior SF6/N2 selectivity

Acute effects of adaptive Deep Brain Stimulation in Parkinson's disease

Background: Beta-based adaptive Deep Brain Stimulation (aDBS) is effective in Parkinson's disease (PD), when assessed in the immediate post-implantation phase. However, the potential benefits of aDBS in patients with electrodes chronically implanted, in whom changes due to the microlesion effect have disappeared, are yet to be assessed. Methods: To determine the acute effectiveness and side-effect profile of aDBS in PD compared to conventional continuous DBS (cDBS) and no stimulation (NoStim), years after DBS implantation, 13 PD patients undergoing battery replacement were pseudo-randomised in a crossover fashion, into three conditions (NoStim, aDBS or cDBS), with a 2-min interval between them. Patient videos were blindly evaluated using a short version of the Unified Parkinson's Disease Rating Scale (subUPDRS), and the Speech Intelligibility Test (SIT). Results: Mean disease duration was 16 years, and the mean time since DBS-implantation was 6.9 years. subUPDRS scores (11 patients tested) were significantly lower both in aDBS (p=<.001), and cDBS (p = .001), when compared to NoStim. Bradykinesia subscores were significantly lower in aDBS (p = .002), and did not achieve significance during cDBS (p = .08), when compared to NoStim. Two patients demonstrated re-emerging tremor during aDBS. SIT scores of patients who presented stimulation-induced dysarthria significantly worsened in cDBS (p = .009), but not in aDBS (p = .407), when compared to NoStim. Overall, stimulation was applied 48.8% of the time during aDBS. Conclusion: Beta-based aDBS is effective in PD patients with bradykinetic phenotypes, delivers less stimulation than cDBS, and potentially has a more favourable speech side-effect profile. Patients with prominent tremor may require a modified adaptive strategy

Experimental Confirmation of a Predicted Porous Hydrogen‐Bonded Organic Framework

AbstractHydrogen‐bonded organic frameworks (HOFs) with low densities and high porosities are rare and challenging to design because most molecules have a strong energetic preference for close packing. Crystal structure prediction (CSP) can rank the crystal packings available to an organic molecule based on their relative lattice energies. This has become a powerful tool for the a priori design of porous molecular crystals. Previously, we combined CSP with structure‐property predictions to generate energy‐structure‐function (ESF) maps for a series of triptycene‐based molecules with quinoxaline groups. From these ESF maps, triptycene trisquinoxalinedione (TH5) was predicted to form a previously unknown low‐energy HOF (TH5‐A) with a remarkably low density of 0.374 g cm−3 and three‐dimensional (3D) pores. Here, we demonstrate the reliability of those ESF maps by discovering this TH5‐A polymorph experimentally. This material has a high accessible surface area of 3,284 m2 g−1, as measured by nitrogen adsorption, making it one of the most porous HOFs reported to date.</jats:p

Sulfone-containing covalent organic frameworks for photocatalytic hydrogen evolution from water

Nature uses organic molecules for light harvesting and photosynthesis, but most man-made water splitting catalysts are inorganic semiconductors. Organic photocatalysts, while attractive because of their synthetic tunability, tend to have low quantum efficiencies for water splitting. Here we present a crystalline covalent organic framework (COF) based on a benzo-bis(benzothiophene sulfone) moiety that shows a much higher activity for photochemical hydrogen evolution than its amorphous or semicrystalline counterparts. The COF is stable under long-term visible irradiation and shows steady photochemical hydrogen evolution with a sacrificial electron donor for at least 50 hours. We attribute the high quantum efficiency of fused-sulfone-COF to its crystallinity, its strong visible light absorption, and its wettable, hydrophilic 3.2 nm mesopores. These pores allow the framework to be dye-sensitized, leading to a further 61% enhancement in the hydrogen evolution rate up to 16.3 mmol g −1 h −1 . The COF also retained its photocatalytic activity when cast as a thin film onto a support