Glaucoma, a progressive optic neuropathy due to retinal ganglion cell (RGC) degeneration, is one of the leading causes of irreversible blindness. Although glaucoma is often associated with elevated intraocular pressure (IOP), IOP elevation is not detected in a significant subset of glaucomas, such as normal tension glaucoma (NTG). Moreover, in some glaucoma patients, significant IOP reduction does not prevent progression of the disease. Thus, understanding IOP-independent mechanisms of RGC loss is important. Here, we show that mice deficient in the glutamate transporters GLAST or EAAC1 demonstrate spontaneous RGC and optic nerve degeneration without elevated IOP. In GLAST-deficient mice, the glutathione level in Müller glia was decreased; administration of glutamate receptor blocker prevented RGC loss. In EAAC1-deficient mice, RGCs were more vulnerable to oxidative stress. These findings suggest that glutamate transporters are necessary both to prevent excitotoxic retinal damage and to synthesize glutathione, a major cellular antioxidant and tripeptide of glutamate, cysteine, and glycine. We believe these mice are the first animal models of NTG that offer a powerful system for investigating mechanisms of neurodegeneration in NTG and developing therapies directed at IOP-independent mechanisms of RGC loss.

Lamellae-forming polystyrene-block-poly(methyl methacrylate) (PS-b-PMMA) films, with bulk period L 0, were directed to assemble on lithographically nanopatterned surfaces. The chemical pattern was comprised of “guiding” stripes of cross-linked polystyrene (X-PS) or poly(methyl methacrylate) (X-PMMA) mats, with width W, and interspatial “background” regions of a random copolymer brush of styrene and methyl methacrylate (P(S-r-MMA)). The fraction of styrene (f) in the brush was varied to control the chemistry of the background regions. The period of the pattern was L s. After assembly, the density of the features (domains) in the block copolymer film was an integer multiple (n) of the density of features of the chemical pattern, where n = L s/L 0. The quality of the assembled PS-b-PMMA films into patterns of dense lines as a function of n, W/L 0, and f was analyzed with top-down scanning electron microscopy. The most effective background chemistry for directed assembly with density multiplication corresponded to a brush chemistry (f) that minimized the interfacial energy between the background regions and the composition of the film overlying the background regions. The three-dimensional structure of the domains within the film was investigated using cross-sectional SEM and Monte Carlo simulations of a coarse-grained model and was found most closely to resemble perpendicularly oriented lamellae when W/L 0 ∼ 0.5–0.6. Directed self-assembly with density multiplication (n = 4) and W/L 0 = 1 or 1.5 yields pattern of high quality, parallel linear structures on the top surface of the assembled films, but complex, three-dimensional structures within the film.

A search for the rare decay K L → π 0 νν was performed. With the data collected in 2015, corresponding to 2.2 × 10 19 protons on target, a single event sensitivity of ð1.30 AE 0.01 stat AE 0.14 syst Þ × 10 −9 was achieved and no candidate events were observed. We set an upper limit of 3.0 × 10 −9 for the branching fraction of K L → π 0 νν at the 90% confidence level (C.L.), which improved the previous limit by almost an order of magnitude. An upper limit for K L → π 0 X 0 was also set as 2.4 × 10 −9 at the 90% C.L., where X 0 is an invisible boson with a mass of 135 MeV=c 2 .

The time evolution of void structures in highly purified polymer latex dispersions was studied with a confocal laser scanning microscope. In such dispersions, which were initially homogeneous, the voids grew with time when the dispersions were kept standing and formed more quickly in the internal material than in material close to the glass-dispersion interface. Void formation is thus not an artifact arising from the presence of the interface. A similar structural inhomogeneity, in apparently homogeneous systems, is discussed for simple ionic solutions, ionic polymer solutions, and Langmuir-Blodgett films.

Cancer gene therapy requires a safe and effective gene delivery system. Polymer- and lipid-coated magnetic nanocrystals have been used to deliver silencing RNA, but synthesizing these magnetic vectors is difficult. Here, we show that a new nanoparticle formulation can be magnetically guided to deliver and silence genes in cells and tumours in mice. This formulation, termed LipoMag, consists of an oleic acid-coated magnetic nanocrystal core and a cationic lipid shell. When compared with the commercially available PolyMag formulation, LipoMag displayed more efficient gene silencing in 9 of 13 cell lines, and better anti-tumour effects when systemically administered to mice bearing gastric tumours. By delivering an optimized sequence of a silencing RNA that targets the epidermal growth factor receptor of tumour vessels, the intended therapeutic benefit was achieved with no evident adverse immune reaction or untoward side effects.