Soluble Guanylate Cyclase α1–Deficient Mice: A Novel Murine Model for Primary Open Angle Glaucoma

Primary open angle glaucoma (POAG) is a leading cause of blindness worldwide. The molecular signaling involved in the pathogenesis of POAG remains unknown. Here, we report that mice lacking the $α_1$ subunit of the nitric oxide receptor soluble guanylate cyclase represent a novel and translatable animal model of POAG, characterized by thinning of the retinal nerve fiber layer and loss of optic nerve axons in the context of an open iridocorneal angle. The optic neuropathy associated with soluble guanylate cyclase $α_1$–deficiency was accompanied by modestly increased intraocular pressure and retinal vascular dysfunction. Moreover, data from a candidate gene association study suggests that a variant in the locus containing the genes encoding for the $α_1$ and $β_1$ subunits of soluble guanylate cyclase is associated with POAG in patients presenting with initial paracentral vision loss, a disease subtype thought to be associated with vascular dysregulation. These findings provide new insights into the pathogenesis and genetics of POAG and suggest new therapeutic strategies for POAG

Sequence-defined multifunctional polyethers via liquid-phase synthesis with molecular sieving

Synthetic chemists have devoted tremendous effort towards the production of precision synthetic polymers with defined sequences and specific functions. However, the creation of a general technology that enables precise control over monomer sequence, with efficient isolation of the target polymers, is highly challenging. Here, we report a robust strategy for the production of sequence-defined synthetic polymers through a combination of liquid-phase synthesis and selective molecular sieving. The polymer is assembled in solution with real-time monitoring to ensure couplings proceed to completion, on a three-armed star-shaped macromolecule to maximize efficiency during the molecular sieving process. This approach is applied to the construction of sequence-defined polyethers, with side-arms at precisely defined locations that can undergo site-selective modification after polymerization. Using this versatile strategy, we have introduced structural and functional diversity into sequence-defined polyethers, unlocking their potential for real-life applications in nanotechnology, healthcare and information storage

Nano-Architecture of nitrogen-doped graphene films synthesized from a solid CN source

New synthesis routes to tailor graphene properties by controlling the concentration and chemical configuration of dopants show great promise. Herein we report the direct reproducible synthesis of 2-3% nitrogen-doped ‘few-layer’ graphene from a solid state nitrogen carbide a-C:N source synthesized by femtosecond pulsed laser ablation. Analytical investigations, including synchrotron facilities, made it possible to identify the configuration and chemistry of the nitrogen-doped graphene films. Auger mapping successfully quantified the 2D distribution of the number of graphene layers over the surface, and hence offers a new original way to probe the architecture of graphene sheets. The films mainly consist in a Bernal ABA stacking three-layer architecture, with a layer number distribution ranging from 2 to 6. Nitrogen doping affects the charge carrier distribution but has no significant effects on the number of lattice defects or disorders, compared to undoped graphene synthetized in similar conditions. Pyridinic, quaternary and pyrrolic nitrogen are the dominant chemical configurations, pyridinic N being preponderant at the scale of the film architecture. This work opens highly promising perspectives for the development of self-organized nitrogen-doped graphene materials, as synthetized from solid carbon nitride, with various functionalities, and for the characterization of 2D materials using a significant new methodology

Consensus Recommendation for Mouse Models of Ocular Hypertension to Study Aqueous Humor Outflow and Its Mechanisms.

Due to their similarities in anatomy, physiology, and pharmacology to humans, mice are a valuable model system to study the generation and mechanisms modulating conventional outflow resistance and thus intraocular pressure. In addition, mouse models are critical for understanding the complex nature of conventional outflow homeostasis and dysfunction that results in ocular hypertension. In this review, we describe a set of minimum acceptable standards for developing, characterizing, and utilizing mouse models of open-angle ocular hypertension. We expect that this set of standard practices will increase scientific rigor when using mouse models and will better enable researchers to replicate and build upon previous findings

Exclusive electrical determination of high-resistance grain-boundaries in poly-graphene

Single layer graphene (SLG), with high optical transparency and electrical conductivity, may potentially be used as flexible transparent electrode in photovoltaics, photo detectors, and flat panel displays. While its optical transmittance exceeds 95% (significantly better than most traditional materials), its sheet resistance (?? poly-G) must be reduced below 10-20??/??? for viable replacement of present Transparent Conducting Oxides (TCOs) like Indium doped Tin Oxide (ITO). However, large scale CVD SLG is typically polycrystalline, consisting of many grains, with neighboring grains separated by high- and low-resistance grain boundaries (HGB and LGB), see Fig. 1 and 7. The HGBs severely limit the (percolating) electronic transport, so that ?? poly-G> 1000??/???. It is therefore important to determine the electronic nature and fraction of HGB to improve transport in polycrystalline SLG

Copercolating Networks: An Approach for Realizing High-Performance Transparent Conductors using Multicomponent Nanostructured Networks

Although transparent conductive oxides such as indium tin oxide (ITO) are widely employed as transparent conducting electrodes (TCEs) for applications such as touch screens and displays, new nanostructured TCEs are of interest for future applications, including emerging transparent and flexible electronics. A number of twodimensional networks of nanostructured elements have been reported, including metallic nanowire networks consisting of silver nanowires, metallic carbon nanotubes (m-CNTs), copper nanowires or gold nanowires, and metallic mesh structures. In these single-component systems, it has generally been difficult to achieve sheet resistances that are comparable to ITO at a given broadband optical transparency. A relatively new third category of TCEs consisting of networks of 1D-1D and 1D-2D nanocomposites (such as silver nanowires and CNTs, silver nanowires and polycrystalline graphene, silver nanowires and reduced graphene oxide) have demonstrated TCE performance comparable to, or better than, ITO. In such hybrid networks, copercolation between the two components can lead to relatively low sheet resistances at nanowire densities corresponding to high optical transmittance. This review provides an overview of reported hybrid networks, including a comparison of the performance regimes achievable with those of ITO and single-component nanostructured networks. The performance is compared to that expected from bulk thin films and analyzed in terms of the copercolation model. In addition, performance characteristics relevant for flexible and transparent applications are discussed. The new TCEs are promising, but significant work must be done to ensure earth abundance, stability, and reliability so that they can eventually replace traditional ITO-based transparent conductors