Molecular and phenotypic characterization of a mouse model of oculopharyngeal muscular dystrophy reveals severe muscular atrophy restricted to fast glycolytic fibres

Oculopharyngeal muscular dystrophy (OPMD) is an adult-onset disorder characterized by ptosis, dysphagia and proximal limb weakness. Autosomal-dominant OPMD is caused by a short (GCG)8–13 expansions within the first exon of the poly(A)-binding protein nuclear 1 gene (PABPN1), leading to an expanded polyalanine tract in the mutated protein. Expanded PABPN1 forms insoluble aggregates in the nuclei of skeletal muscle fibres. In order to gain insight into the different physiological processes affected in OPMD muscles, we have used a transgenic mouse model of OPMD (A17.1) and performed transcriptomic studies combined with a detailed phenotypic characterization of this model at three time points. The transcriptomic analysis revealed a massive gene deregulation in the A17.1 mice, among which we identified a significant deregulation of pathways associated with muscle atrophy. Using a mathematical model for progression, we have identified that one-third of the progressive genes were also associated with muscle atrophy. Functional and histological analysis of the skeletal muscle of this mouse model confirmed a severe and progressive muscular atrophy associated with a reduction in muscle strength. Moreover, muscle atrophy in the A17.1 mice was restricted to fast glycolytic fibres, containing a large number of intranuclear inclusions (INIs). The soleus muscle and, in particular, oxidative fibres were spared, even though they contained INIs albeit to a lesser degree. These results demonstrate a fibre-type specificity of muscle atrophy in this OPMD model. This study improves our understanding of the biological pathways modified in OPMD to identify potential biomarkers and new therapeutic targets.

The formation of ice in a long-lived supercooled layer cloud

This article focuses on the characteristics of persistent thin single-layer mixed-phase clouds. We seek to answer two important questions: (i) how does ice continually nucleate and precipitate from these clouds, without the available ice nuclei becoming depleted? (ii) how do the supercooled liquid droplets persist in spite of the net flux of water vapour to the growing ice crystals? These questions are answered quantitatively using in situ and radar observations of a long-lived mixed-phase cloud layer over the Chilbolton Observatory. Doppler radar measurements show that the top 500 m of cloud (the top 250 m of which is mixed-phase, with ice virga beneath) is turbulent and well-mixed, and the liquid water content is adiabatic. This well-mixed layer is bounded above and below by stable layers. This inhibits entrainment of fresh ice nuclei into the cloud layer, yet our in situ and radar observations show that a steady flux of ≈100 m−2s−1 ice crystals fell from the cloud over the course of ∼1 day. Comparing this flux to the concentration of conventional ice nuclei expected to be present within the well-mixed layer, we find that these nuclei would be depleted within less than 1 h. We therefore argue that nucleation in these persistent supercooled clouds is strongly time-dependent in nature, with droplets freezing slowly over many hours, significantly longer than the few seconds residence time of an ice nucleus counter. Once nucleated, the ice crystals are observed to grow primarily by vapour deposition, because of the low liquid water path (21 g m−2) yet vapour-rich environment. Evidence for this comes from high differential reflectivity in the radar observations, and in situ imaging of the crystals. The flux of vapour from liquid to ice is quantified from in situ measurements, and we show that this modest flux (3.3 g m−2h−1) can be readily offset by slow radiative cooling of the layer to space.

Potential reduction of concrete deterioration through controlled DEF in hydrated concrete

Delayed ettringite formation (DEF) is a chemical reaction with proven damaging effects on hydrated concrete. Ettringite crystals can cause cracks and their widening due to pressure on cracked walls caused by the positive volume difference in the reaction. Concrete may show improvements in strength at early ages but further growth of cracks causes widening and spreading through the concrete structure. In this study, finely dispersed crystallization nuclei achieved by adding air-entraining agent (AEA) and short vibration of specimens is presented as the main prerequisite for reducing DEF-induced deterioration of hydrated concrete. The study presents the method and mechanism for obtaining the required nucleation. Controlling long-term DEF by providing AEA-induced crystallisation nuclei, prevented excessive and rapid initial strength improvements, and resulted in a slight increase of compressive strength of fine grained concrete with only marginally lower density.

Modelling the effects of gravity waves on stratocumulus clouds observed during VOCALS-UK

During the VOCALS campaign spaceborne satellite observations showed that travelling gravity wave packets, generated by geostrophic adjustment, resulted in perturbations to marine boundary layer (MBL) clouds over the south-east Pacific Ocean (SEP). Often, these perturbations were reversible in that passage of the wave resulted in the clouds becoming brighter (in the wave crest), then darker (in the wave trough) and subsequently recovering their properties after the passage of the wave. However, occasionally the wave packets triggered irreversible changes to the clouds, which transformed from closed mesoscale cellular convection to open form. In this paper we use large eddy simulation (LES) to examine the physical mechanisms that cause this transition. Specifically, we examine whether the clearing of the cloud is due to (i) the wave causing additional cloud-top entrainment of warm, dry air or (ii) whether the additional condensation of liquid water onto the existing drops and the subsequent formation of drizzle are the important mechanisms. We find that, although the wave does cause additional drizzle formation, this is not the reason for the persistent clearing of the cloud; rather it is the additional entrainment of warm, dry air into the cloud followed by a reduction in longwave cooling, although this only has a significant effect when the cloud is starting to decouple from the boundary layer. The result in this case is a change from a stratocumulus to a more patchy cloud regime. For the simulations presented here, cloud condensation nuclei (CCN) scavenging did not play an important role in the clearing of the cloud. The results have implications for understanding transitions between the different cellular regimes in marine boundary layer (MBL) clouds.

Impact of the modal aerosol scheme GLOMAP-mode on aerosol forcing in the Hadley Centre Global Environmental Model

The Hadley Centre Global Environmental Model (HadGEM) includes two aerosol schemes: the Coupled Large-scale Aerosol Simulator for Studies in Climate (CLASSIC), and the new Global Model of Aerosol Processes (GLOMAP-mode). GLOMAP-mode is a modal aerosol microphysics scheme that simulates not only aerosol mass but also aerosol number, represents internally-mixed particles, and includes aerosol microphysical processes such as nucleation. In this study, both schemes provide hindcast simulations of natural and anthropogenic aerosol species for the period 2000–2006. HadGEM simulations of the aerosol optical depth using GLOMAP-mode compare better than CLASSIC against a data-assimilated aerosol re-analysis and aerosol ground-based observations. Because of differences in wet deposition rates, GLOMAP-mode sulphate aerosol residence time is two days longer than CLASSIC sulphate aerosols, whereas black carbon residence time is much shorter. As a result, CLASSIC underestimates aerosol optical depths in continental regions of the Northern Hemisphere and likely overestimates absorption in remote regions. Aerosol direct and first indirect radiative forcings are computed from simulations of aerosols with emissions for the year 1850 and 2000. In 1850, GLOMAP-mode predicts lower aerosol optical depths and higher cloud droplet number concentrations than CLASSIC. Consequently, simulated clouds are much less susceptible to natural and anthropogenic aerosol changes when the microphysical scheme is used. In particular, the response of cloud condensation nuclei to an increase in dimethyl sulphide emissions becomes a factor of four smaller. The combined effect of different 1850 baselines, residence times, and abilities to affect cloud droplet number, leads to substantial differences in the aerosol forcings simulated by the two schemes. GLOMAP-mode finds a presentday direct aerosol forcing of −0.49Wm−2 on a global average, 72% stronger than the corresponding forcing from CLASSIC. This difference is compensated by changes in first indirect aerosol forcing: the forcing of −1.17Wm−2 obtained with GLOMAP-mode is 20% weaker than with CLASSIC. Results suggest that mass-based schemes such as CLASSIC lack the necessary sophistication to provide realistic input to aerosol-cloud interaction schemes. Furthermore, the importance of the 1850 baseline highlights how model skill in predicting present-day aerosol does not guarantee reliable forcing estimates. Those findings suggest that the more complex representation of aerosol processes in microphysical schemes improves the fidelity of simulated aerosol forcings.

A review of measurement-based assessments of the aerosol direct radiative effect and forcing

Aerosols affect the Earth's energy budget directly by scattering and absorbing radiation and indirectly by acting as cloud condensation nuclei and, thereby, affecting cloud properties. However, large uncertainties exist in current estimates of aerosol forcing because of incomplete knowledge concerning the distribution and the physical and chemical properties of aerosols as well as aerosol-cloud interactions. In recent years, a great deal of effort has gone into improving measurements and datasets. It is thus feasible to shift the estimates of aerosol forcing from largely model-based to increasingly measurement-based. Our goal is to assess current observational capabilities and identify uncertainties in the aerosol direct forcing through comparisons of different methods with independent sources of uncertainties. Here we assess the aerosol optical depth (τ), direct radiative effect (DRE) by natural and anthropogenic aerosols, and direct climate forcing (DCF) by anthropogenic aerosols, focusing on satellite and ground-based measurements supplemented by global chemical transport model (CTM) simulations. The multi-spectral MODIS measures global distributions of aerosol optical depth (τ) on a daily scale, with a high accuracy of ±0.03±0.05τ over ocean. The annual average τ is about 0.14 over global ocean, of which about 21%±7% is contributed by human activities, as estimated by MODIS fine-mode fraction. The multi-angle MISR derives an annual average AOD of 0.23 over global land with an uncertainty of ~20% or ±0.05. These high-accuracy aerosol products and broadband flux measurements from CERES make it feasible to obtain observational constraints for the aerosol direct effect, especially over global the ocean. A number of measurement-based approaches estimate the clear-sky DRE (on solar radiation) at the top-of-atmosphere (TOA) to be about -5.5±0.2 Wm-2 (median ± standard error from various methods) over the global ocean. Accounting for thin cirrus contamination of the satellite derived aerosol field will reduce the TOA DRE to -5.0 Wm-2. Because of a lack of measurements of aerosol absorption and difficulty in characterizing land surface reflection, estimates of DRE over land and at the ocean surface are currently realized through a combination of satellite retrievals, surface measurements, and model simulations, and are less constrained. Over the oceans the surface DRE is estimated to be -8.8±0.7 Wm-2. Over land, an integration of satellite retrievals and model simulations derives a DRE of -4.9±0.7 Wm-2 and -11.8±1.9 Wm-2 at the TOA and surface, respectively. CTM simulations derive a wide range of DRE estimates that on average are smaller than the measurement-based DRE by about 30-40%, even after accounting for thin cirrus and cloud contamination. A number of issues remain. Current estimates of the aerosol direct effect over land are poorly constrained. Uncertainties of DRE estimates are also larger on regional scales than on a global scale and large discrepancies exist between different approaches. The characterization of aerosol absorption and vertical distribution remains challenging. The aerosol direct effect in the thermal infrared range and in cloudy conditions remains relatively unexplored and quite uncertain, because of a lack of global systematic aerosol vertical profile measurements. A coordinated research strategy needs to be developed for integration and assimilation of satellite measurements into models to constrain model simulations. Enhanced measurement capabilities in the next few years and high-level scientific cooperation will further advance our knowledge.

A mathematical model of crystallization in an emulsion

A mathematical model incorporating many of the important processes at work in the crystallization of emulsions is presented. The model describes nucleation within the discontinuous domain of an emulsion, precipitation in the continuous domain, transport of monomers between the two domains, and formation and subsequent growth of crystals in both domains. The model is formulated as an autonomous system of nonlinear, coupled ordinary differential equations. The description of nucleation and precipitation is based upon the Becker–Döring equations of classical nucleation theory. A particular feature of the model is that the number of particles of all species present is explicitly conserved; this differs from work that employs Arrhenius descriptions of nucleation rate. Since the model includes many physical effects, it is analyzed in stages so that the role of each process may be understood. When precipitation occurs in the continuous domain, the concentration of monomers falls below the equilibrium concentration at the surface of the drops of the discontinuous domain. This leads to a transport of monomers from the drops into the continuous domain that are then incorporated into crystals and nuclei. Since the formation of crystals is irreversible and their subsequent growth inevitable, crystals forming in the continuous domain effectively act as a sink for monomers “sucking” monomers from the drops. In this case, numerical calculations are presented which are consistent with experimental observations. In the case in which critical crystal formation does not occur, the stationary solution is found and a linear stability analysis is performed. Bifurcation diagrams describing the loci of stationary solutions, which may be multiple, are numerically calculated.

Development of frazil modelling in ice shelf water plumes

Abstract Preliminary results are presented from a modelling study directed at the spatial variation of frazil ice formation and its effects on flow underneath large ice shelves. The chosen plume and frazil models are briefly introduced, and results from two simplified cases are outlined. It is found that growth and melting dominate the frazil model in the short term. Secondary nucleation converts larger crystals into several nuclei due to crystal collisions (microattrition) and fluid shear and therefore governs the ice crystal dynamics after the initial supercooling has been quenched. Frazil formation is found to have a significant depth-dependence in an idealised study of an Ice Shelf Water plume. Finally, plans for more extensive and realistic studies are discussed.

Aerosol impacts on drizzle properties in warm clouds from ARM Mobile Facility maritime and continental deployments

We have extensively evaluated the response of cloud-base drizzle rate (Rcb; mm day–1) in warm clouds to liquid water path (LWP; g m–2) and to cloud condensation nuclei (CCN) number concentration (NCCN; cm–3), an aerosol proxy. This evaluation is based on a 19-month long dataset of Doppler radar, lidar, microwave radiometers and aerosol observing systems from the Atmospheric Radiation Measurement (ARM) Mobile Facility deployments at the Azores and in Germany. Assuming 0.55% supersaturation to calculate NCCN, we found a power law , indicating that Rcb decreases by a factor of 2–3 as NCCN increases from 200 to 1000 cm–3 for fixed LWP. Additionally, the precipitation susceptibility to NCCN ranges between 0.5 and 0.9, in agreement with values from simulations and aircraft measurements. Surprisingly, the susceptibility of the probability of precipitation from our analysis is much higher than that from CloudSat estimates, but agrees well with simulations from a multi-scale high-resolution aerosol-climate model. Although scale issues are not completely resolved in the intercomparisons, our results are encouraging, suggesting that it is possible for multi-scale models to accurately simulate the response of LWP to aerosol perturbations.

Enhancing the crystallization and orientation of electrospinning poly (lactic acid) (PLLA) by combining with additives

PLLA is a thermoplastic biopolymer and can be used in industrial applications for medical and filtration applications. The brittleness of PLLA is attributed to slow crystallization rates and its glass transition temperature (Tg) is high (60 °C); for this reason, its applications are limited. The orientation, morphology, and crystal structure of the electrospun fibers was investigated by SEM, POM, DSC, FTIR, XRD, and SAXS. Combining with additives leads to a large decrease of fiber diameter, viscosity, and changes of fiber morphology and crystal structure compared to pure PLLA. DSC showed that the Tg of PLLA decreased about 15 °C and there was no change in relaxation enthalpy by the addition of plasticizer. FT-IR indicate a strong interaction between PLLA and additives; a new band appears in the PLLA blend at 1,756 cm−1 at room temperature as a crystalline band without any annealing. In addition, WAXD indicated that the intensities of the two peaks at (200/110) and (203) increased for the blend at room temperature without any annealing in comparison with PLLA; this means that PHB crystallizes in the amorphous region of PLLA. The POM experiments agree with the results from DSC, FTIR, and WAXS measurements, confirming that adding PHB results in an increase in the number of nuclei with much smaller spherulites and enhances the crystallization behavior of this material, thereby improving its potential for applications.

What do cosmogenic isotopes tell us about past solar forcing of climate?

In paleoclimate studies, cosmogenic isotopes are frequently used as proxy indicators of past variations in solar irradiance on centennial and millennial timescales. These isotopes are spallation products of galactic cosmic rays (GCRs) impacting Earth’s atmosphere, which are deposited and stored in terrestrial reservoirs such as ice sheets, ocean sediments and tree trunks. On timescales shorter than the variations in the geomagnetic field, they are modulated by the heliosphere and thus they are, strictly speaking, an index of heliospheric variability rather than one of solar variability. Strong evidence of climate variations associated with the production (as opposed to the deposition) of these isotopes is emerging. This raises a vital question: do cosmic rays have a direct influence on climate or are they a good proxy indicator for another factor that does (such as the total or spectral solar irradiance)? The former possibility raises further questions about the possible growth of air ions generated by cosmic rays into cloud condensation nuclei and/or the modulation of the global thunderstorm electric circuit. The latter possibility requires new understanding about the required relationship between the heliospheric magnetic fields that scatter cosmic rays and the photospheric magnetic fields which modulate solar irradiance.

Intercomparison and evaluation of global aerosol microphysical properties among AeroCom models of a range of complexity

Many of the next generation of global climate models will include aerosol schemes which explicitly simulate the microphysical processes that determine the particle size distribution. These models enable aerosol optical properties and cloud condensation nuclei (CCN) concentrations to be determined by fundamental aerosol processes, which should lead to a more physically based simulation of aerosol direct and indirect radiative forcings. This study examines the global variation in particle size distribution simulated by 12 global aerosol microphysics models to quantify model diversity and to identify any common biases against observations. Evaluation against size distribution measurements from a new European network of aerosol supersites shows that the mean model agrees quite well with the observations at many sites on the annual mean, but there are some seasonal biases common to many sites. In particular, at many of these European sites, the accumulation mode number concentration is biased low during winter and Aitken mode concentrations tend to be overestimated in winter and underestimated in summer. At high northern latitudes, the models strongly underpredict Aitken and accumulation particle concentrations compared to the measurements, consistent with previous studies that have highlighted the poor performance of global aerosol models in the Arctic. In the marine boundary layer, the models capture the observed meridional variation in the size distribution, which is dominated by the Aitken mode at high latitudes, with an increasing concentration of accumulation particles with decreasing latitude. Considering vertical profiles, the models reproduce the observed peak in total particle concentrations in the upper troposphere due to new particle formation, although modelled peak concentrations tend to be biased high over Europe. Overall, the multi-model-mean data set simulates the global variation of the particle size distribution with a good degree of skill, suggesting that most of the individual global aerosol microphysics models are performing well, although the large model diversity indicates that some models are in poor agreement with the observations. Further work is required to better constrain size-resolved primary and secondary particle number sources, and an improved understanding of nucleation and growth (e.g. the role of nitrate and secondary organics) will improve the fidelity of simulated particle size distributions.

1H-13C HSQC NMR spectroscopy for estimating procyanidin/prodelphinidin and cis/trans-flavan-3-ol ratios of condensed tannin samples: correlation with thiolysis

Studies with a diverse array of 22 purified condensed tannin (CT) samples from nine plant species demonstrated that procyanidin/prodelphinidin (PC/PD) and cis/trans-flavan-3-ol ratios can be appraised by 1H-13C HSQC NMR spectroscopy. The method was developed from samples containing 44 to ~100% CT, PC/PD ratios ranging from 0/100 to 99/1, and cis/trans ratios from 58/42 to 95/5 as determined by thiolysis with benzyl mercaptan. Integration of cross-peak contours of H/C-6' signals from PC and of H/C-2',6' signals from PD yielded nuclei adjusted estimates that were highly correlated with PC/PD ratios obtained by thiolysis (R2 = 0.99). Cis/trans-flavan-3-ol ratios, obtained by integration of the respective H/C-4 cross-peak contours, were also related to determinations made by thiolysis (R2 = 0.89). Overall, 1H-13C HSQC NMR spectroscopy appears to be a viable alternative to thiolysis for estimating PC/PD and cis/trans ratios of CT, if precautions are taken to avoid integration of cross-peak contours of contaminants.

First Results with the RISING active stopper

This paper outlines some of the physics opportunities available with the GSI RISING active stopper and presents preliminary results from an experiment aimed at performing beta-delayed gamma-ray spectroscopic studies in heavy-neutron-rich nuclei produced following the projectile fragmentation of a 1 GeV per nucleon 208Pb primary beam. The energy response of the silicon active stopping detector for both heavy secondary fragments and beta-particles is demonstrated and preliminary results on the decays of neutron-rich Tantalum (Ta) to Tungsten (W) isotopes are presented as examples of the potential of this technique to allow new structural studies in hitherto experimentally unreachable heavy, neutron-rich nuclei. The resulting spectral information inferred from excited states in the tungsten daughter nuclei are compared with results from axially symmetric Hartree–Fock calculations of the nuclear shape and suggest a change in ground state structure for the N = 116 isotone 190W compared to the lighter isotopes of this element.

Role of the Skyrme tensor force in heavy-ion fusion

We make use of the Skyrme effective nuclear interaction within the time-dependent Hartree-Fock framework to assess the effect of inclusion of the tensor terms of the Skyrme interaction on the fusion window of the 16O–16O reaction. We find that the lower fusion threshold, around the barrier, is quite insensitive to these details of the force, but the higher threshold, above which the nuclei pass through each other, changes by several MeV between different tensor parametrisations. The results suggest that eventually fusion properties may become part of the evaluation or fitting process for effective nuclear interactions.