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Glaucoma is the leading cause of irreversible blindness. Currently, most therapeutic strategies aim to reduce elevated intraocular pressure (EIOP), but this does not always halt disease progression. Evidence suggests a role for T cells in glaucoma pathogenesis, but the underlying mechanisms remain largely unknown. Here, we found that the percentage of circulating CD4+ T cells expressing a gut-homing integrin β7 was increased in patients with glaucoma and was associated with disease stage. In an EIOP-triggered glaucoma mouse model, β7+ CD4+ T cells infiltrated the retina in the progressive phase of glaucoma via eliciting retinal endothelial cell expression of mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1). MAdCAM-1 was minimally detected in retinas of healthy mice, and neutralization with an MAdCAM-1 antibody ameliorated retinal ganglion cell (RGC) loss and glial activity in mice with glaucoma. We furthermore found that EIOP-induced β7+ CD4+ T cells homed to the gut during the acute phase of glaucoma, which was essential for progressive RGC damage in diseased mice. Gut-homing β7+ CD4+ T cells underwent transcriptional reprogramming, showing up-regulated pathways enriched in autoimmune diseases, bacteria responses, mucosal immunity, and glial activity. Gut-homing β7+ CD4+ T cells gained the competence to induce retinal MAdCAM-1 expression and to cross the blood-retina barrier. Together, our study reveals a role of gut-licensed β7+ CD4+ T cells and MAdCAM-1 in RGC degeneration and emphasizes the importance of the "gut-retina" axis in glaucoma. Editor's summary: T cells are likely involved in glaucoma pathogenesis, but how they gain retinal access remains elusive. He and colleagues discovered an association of CD4+ T cells that express the gut homing integrin β7 with glaucoma disease severity in patients. Experiments with a glaucoma mouse model showed that β7+ CD4+ T cells need a detour to the gut, where they undergo genetic reprogramming to gain retinal access. Blocking mucosal addressin cell adhesion molecule 1 prevented retinal infiltration of β7+ CD4+ T cells and ameliorated the loss of retinal ganglion cells. These findings highlight the importance of the gut-retina axis for glaucoma disease progression. Daniela Neuhofer [ABSTRACT FROM AUTHOR]

In this paper, a polycarboxylic water reducing agent was synthesized by using Methylallyl polyethylene glycol (HPEG) with molecular weight of 1200, 2400, 2800 and 3400 under the same conditions, C80 concrete tests were performed on these four molecular weight superplasticizers, verify the effect of different molecular weight polycarboxylic acid water reducer in C80 pumping concrete, finally, a kind of low molecular weight polycarboxylic acid water reducer with viscosity reducing effect in high-grade concrete is obtained, which can promote pumping of high-grade concrete.

We simulate the formation and collapse of pre-stellar cores at few-au resolution in a set of radiation-magnetohydrodynamic simulations of giant molecular clouds (GMCs) using the grid-based code RAMSES-RT. We adopt, for the first time to our best knowledge, realistic initial/boundary conditions by zooming in on to individual massive pre-stellar cores within the GMC. We identify two distinct modes of fragmentation: 'quasi-spherical' and 'filamentary'. In both modes, the fragments eventually become embedded in a quasi-steady accretion disc or toroid with radii ∼500–5000 au and opening angles H / R ∼ 0.5 − 1. The discs/toroids are Toomre stable but the accreted pre-existing fragments are found orbiting the outer disc, appearing as disc fragmentation. Each core converts nearly 100 per cent of the gas mass into a few massive stars forming near the disc centre. Large and massive discs around high-mass stars are supported by magnetic pressure in the outer disc, at radii >200–1000 au, and turbulent pressure in the inner disc. The most massive core accretes several times more mass than its initial mass, forming a cluster of 8 massive (proto)stars enshrouded by a toroid, suggesting a competitive accretion scenario for the formation of stars above ∼30 M⊙. We also find that the H  ii regions produced by a single massive star remain trapped in the dense circumstellar discs for a few hundred kiloyears, while the dynamic motions of massive stars in wide binaries or multiple systems displace the stars from the densest parts of the disc, allowing UV radiation to escape producing steady or pulsating bipolar H  ii regions. [ABSTRACT FROM AUTHOR]

Relevance Vector Machine (RVM) is a supervised learning algorithm extended from Support Vector Machine based on the Bayesian sparsity model. Relevance Vector Machine classification suffers from theoretical limitations and computational inefficiency mainly because there is no closed‐form solution for the posterior of the weight parameters. We propose two advanced Bayesian approaches for RVM classification, namely the Enhanced RVM and the Reinforced RVM, to perfect the theoretic framework of RVM and extend the algorithm to the imbalanced data problem, which has an arresting skew in data size between classes. First, the Enhanced RVM conducts a strict Bayesian sampling process instead of the approximation method in the original one to remedy its theoretic limitations, especially the non‐convergence of the iterations. Secondly, we conjecture that the hierarchical prior makes the Reinforced RVM achieve consistent estimations of the quantities of interest compared with the non‐consistent estimations of the original RVM. Consistency is necessary for RVM classification since it makes the model more stable and localises the relevant vectors more accurately in the imbalanced data problem. The two‐level prior also renders the Reinforced one competitive in the imbalanced data problem by building the inner connection of parameter dimensions and alloting a more vital relevance to the small class data weight parameter. The theoretic proofs and several numeric studies demonstrate the merits of our two proposed algorithms. [ABSTRACT FROM AUTHOR]