Cholinergic neural activity directs retinal layer-specific angiogenesis and blood retinal barrier formation.

Blood vessels in the central nervous system (CNS) develop unique features, but the contribution of CNS neurons to regulating those features is not fully understood. We report that inhibiting spontaneous cholinergic activity or reducing starburst amacrine cell numbers prevents invasion of endothelial cells into the deep layers of the retina and causes blood-retinal-barrier (BRB) dysfunction in mice. Vascular endothelial growth factor (VEGF), which drives angiogenesis, and Norrin, a Wnt ligand that induces BRB properties, are decreased after activity blockade. Exogenous VEGF restores vessel growth but not BRB function, whereas stabilizing beta-catenin in endothelial cells rescues BRB dysfunction but not vessel formation. We further identify that inhibiting cholinergic activity reduces angiogenesis during oxygen-induced retinopathy. Our findings demonstrate that neural activity lies upstream of VEGF and Norrin, coordinating angiogenesis and BRB formation. Neural activity originating from specific neural circuits may be a general mechanism for driving regional angiogenesis and barrier formation across CNS development

Autoantibodies against retinal proteins in paraneoplastic and autoimmune retinopathy

BACKGROUND: Autoimmune retinal degeneration may occur in patients who present with sudden or, less commonly, subacute loss of vision of retinal origin, associated with an abnormal ERG, through the action of autoantibodies against retinal proteins. Often the patients are initially diagnosed with or suspected of having a paraneoplastic retinopathy (PR), such as cancer-associated retinopathy (CAR). However, there is limited information on the occurrence, the specificity of autoantibodies in these patients, and their association with clinical symptoms. METHODS: Sera were obtained from 193 retinopathy patients who presented with clinical symptoms resembling PR or autoimmune retinopathy (AR), including sudden painless loss of vision, typically associated with visual field defects and photopsias, and abnormal rod and/or cone responses on the electroretinogram (ERG). Sera were tested for the presence of anti-retinal autoantibodies by Western blot analysis using proteins extracted from human retina and by immunohistochemistry. Autoantibody titers against recoverin and enolase were measured by ELISA. RESULTS: We identified a higher prevalence of anti-retinal autoantibodies in retinopathy patients. Ninety-one patients' sera (47.1%) showed autoantibodies of various specificities with a higher incidence of antibodies present in retinopathy patients diagnosed with cancer (33/52; 63.5%; p = 0.009) than in retinopathy patients without cancer (58/141; 41.1%). The average age of PR patients was 62.0 years, and that of AR patients was 55.9 years. Autoantibodies against recoverin (p23) were only present in the sera of PR patients, autoantibodies against unknown p35 were more common in patients with AR, while anti-enolase (anti-p46) autoantibodies were nearly equally distributed in the sera of patients with PR and those with AR. In the seropositive patients, the autoantibodies persisted over a long period of time – from months to years. A rebound in anti-recoverin autoantibody titer was found to be associated with exacerbations in visual symptoms but not in the recurrence of cancer. When compared to sera from healthy subjects, autoantibodies against retinal proteins from both groups of patients were cytotoxic to retinal cells, indicating their pathogenic potential. CONCLUSIONS: These studies showed that patients with sudden or subacute, unexplained loss of vision of retinal origin have anti-retinal antibodies in a broad range of specificity and indicate the need for autoantibody screening. Follow-up tests of antibody levels may be useful as a biomarker of disease activity associated with worsening of vision. Moreover, the heterogeneity in autoantibody specificity may explain the variation and complexity of clinical symptoms in retinopathy patients

Pseudorehearsal in value function approximation

Catastrophic forgetting is of special importance in reinforcement learning, as the data distribution is generally non-stationary over time. We study and compare several pseudorehearsal approaches for Q-learning with function approximation in a pole balancing task. We have found that pseudorehearsal seems to assist learning even in such very simple problems, given proper initialization of the rehearsal parameters

On the implications of aerosol liquid water and phase separation for modeled organic aerosol mass

Water is an important component of PM2.5 Many traditional SOA species are highly soluble and thus can be considered extractable Water can influence the partitioning of compounds traditionally considered insoluble in models Organic aerosol takes up water according to RH Organic aerosol interacts with inorganic water Deviations in ideality (solubility) must be considered

A review of physical supply and EROI of fossil fuels in China

This paper reviews China’s future fossil fuel supply from the perspectives of physical output and net energy output. Comprehensive analyses of physical output of fossil fuels suggest that China’s total oil production will likely reach its peak, at about 230 Mt/year (or 9.6 EJ/year), in 2018; its total gas production will peak at around 350 Bcm/year (or 13.6 EJ/year) in 2040, while coal production will peak at about 4400 Mt/year (or 91.9 EJ/year) around 2020 or so. In terms of the forecast production of these fuels, there are significant differences among current studies. These differences can be mainly explained by different ultimately recoverable resources assumptions, the nature of the models used, and differences in the historical production data. Due to the future constraints on fossil fuels production, a large gap is projected to grow between domestic supply and demand, which will need to be met by increasing imports. Net energy analyses show that both coal and oil and gas production show a steady declining trend of EROI (energy return on investment) due to the depletion of shallow-buried coal resources and conventional oil and gas resources, which is generally consistent with the approaching peaks of physical production of fossil fuels. The peaks of fossil fuels production, coupled with the decline in EROI ratios, are likely to challenge the sustainable development of Chinese society unless new abundant energy resources with high EROI values can be found

The Star Formation in Radio Survey: Jansky Very Large Array 33 GHz Observations of Nearby Galaxy Nuclei and Extranuclear Star-Forming Regions

We present 33 GHz imaging for 112 pointings towards galaxy nuclei and extranuclear star-forming regions at $\approx$2" resolution using the Karl G. Jansky Very Large Array (VLA) as part of the Star Formation in Radio Survey. A comparison with 33 GHz Robert C. Byrd Green Bank Telescope single-dish observations indicates that the interferometric VLA observations recover $78\pm4$ of the total flux density over 25" regions ($\approx$ kpc-scales) among all fields. On these scales, the emission being resolved out is most likely diffuse non-thermal synchrotron emission. Consequently, on the $\approx30-300$ pc scales sampled by our VLA observations, the bulk of the 33 GHz emission is recovered and primarily powered by free-free emission from discrete HII regions, making it an excellent tracer of massive star formation. Of the 225 discrete regions used for aperture photometry, 162 are extranuclear (i.e., having galactocentric radii $r_{\rm G} \geq 250$ pc) and detected at $>3\sigma$ significance at 33 GHz and in H$\alpha$. Assuming a typical 33 GHz thermal fraction of 90 %, the ratio of optically-thin 33 GHz-to-uncorrected H$\alpha$ star formation rates indicate a median extinction value on $\approx30-300$ pc scales of $A_{\rm H\alpha} \approx 1.26\pm0.09$ mag with an associated median absolute deviation of 0.87 mag. We find that 10 % of these sources are "highly embedded" (i.e., $A_{\rm H\alpha}\gtrsim3.3$ mag), suggesting that on average HII regions remain embedded for $\lesssim1$ Myr. Finally, we find the median 33 GHz continuum-to-H$\alpha$ line flux ratio to be statistically larger within $r_{\rm G}<250$ pc relative the outer-disk regions by a factor of $1.82\pm0.39$, while the ratio of 33 GHz-to-24 $\mu$m flux densities are lower by a factor of $0.45\pm0.08$, which may suggest increased extinction in the central regions.E.J.M. acknowledges the hospitality of the Aspen Center for Physics, which is supported by National Science Foundation grant No. PHY-1066293. The National Radio Astronomy Observatory is a facility of the National Science Foundation operated under cooperative agreement by Associated Universities, Inc. This research made use of APLpy, an open-source plotting package for Python hosted at http://aplpy.github.com

Should red cell transfusion be individualized? Yes

SCOPUS: ed.jinfo:eu-repo/semantics/publishe

Dotted crystallisation: nucleation accelerated, regulated, and guided by carbon dots

Crystallisation from solution is an important process in pharmaceutical industries and is commonly used to purify active pharmaceutical ingredients. Crystallisation involves phase change and the mechanisms involved are random which makes the process stochastic. This creates a variation in the time required to reach a fixed percentage of yield from batch to batch. It is essential to regulate the batch crystallisation process and make it more predictable for industrial applications for the ease of process chain scheduling of upstream and downstream unit operations. In this work, we propose a new technique called dotted crystallisation, where carbon dots are used to dictate and regulate events associated with nucleation and crystallisation processes. Following the rules of two-step nucleation theory, the carbon dots intentionally added to a supersaturated solution of curcumin anchors the crystallising compound to form prenucleation clusters that evolve into stable nuclei. Using curcumin as a model compound, we showed that the nucleation of this compound in isopropanol can be regulated, and the nucleation rate can be improved via addition of small quantities of carbon dots to the supersaturated solution. Our results confirmed that the nucleation rate of curcumin by dotted crystallisation was roughly four times higher than the nucleation rate by conventional cooling crystallisation and produced smaller sized crystals with a narrow size distribution

Naked mole-rats have distinctive cardiometabolic and genetic adaptations to their underground low-oxygen lifestyles.

The naked mole-rat Heterocephalus glaber is a eusocial mammal exhibiting extreme longevity (37-year lifespan), extraordinary resistance to hypoxia and absence of cardiovascular disease. To identify the mechanisms behind these exceptional traits, metabolomics and RNAseq of cardiac tissue from naked mole-rats was compared to other African mole-rat genera (Cape, Cape dune, Common, Natal, Mahali, Highveld and Damaraland mole-rats) and evolutionarily divergent mammals (Hottentot golden mole and C57/BL6 mouse). We identify metabolic and genetic adaptations unique to naked mole-rats including elevated glycogen, thus enabling glycolytic ATP generation during cardiac ischemia. Elevated normoxic expression of HIF-1α is observed while downstream hypoxia responsive-genes are down-regulated, suggesting adaptation to low oxygen environments. Naked mole-rat hearts show reduced succinate levels during ischemia compared to C57/BL6 mouse and negligible tissue damage following ischemia-reperfusion injury. These evolutionary traits reflect adaptation to a unique hypoxic and eusocial lifestyle that collectively may contribute to their longevity and health span

A constitutive model for cytoskeletal contractility of smooth muscle cells

The constitutive model presented in this article aims to describe the main bio-chemo-mechanical features involved in the contractile response of smooth muscle cells, in which the biochemical response is modelled by extending the four-state Hai–Murphy model to isotonic contraction of the cells and the mechanical response is mainly modelled based on the phosphorylation-dependent hyperbolic relation between isotonic shortening strain rate and tension. The one-dimensional version of the model is used to simulate shortening-induced deactivation with good agreement with selected experimental measurements. The results suggest that the Hai–Murphy biochemical model neglects the strain rate effect on the kinetics of cross-bridge interactions with actin filaments in the isotonic contractions. The two-dimensional version and three-dimensional versions of the model are developed using the homogenization method under finite strain continuum mechanics framework. The two-dimensional constitutive model is used to simulate swine carotid media strips under electrical field stimulation, experimentally investigated by Singer and Murphy, and contraction of a hollow airway and a hollow arteriole buried in a soft matrix subjected to multiple calcium ion stimulations. It is found that the transverse deformation may have significant influence on the response of the swine carotid medium. In both cases, the orientation of the maximal value of attached myosin is aligned with the orientation of maximum principal stress