Defying Disaster

The tremendous growth in the serious games market presents the opportunity to help people learn through playing games. Defying Disaster is a 2D side scroller serious game designed to teach people how to prepare for and handle an earthquake. Players do a series of mini games that provide earthquake survival tips while interacting with a larger world after an earthquake disaster. An evaluation with thirty people compared learning disaster knowledge through reading materials versus playing games. The results show people learn better through playing Defying Disaster than reading materials

RAGE Mediates Accelerated Diabetic Vein Graft Atherosclerosis Induced by Combined Mechanical Stress and AGEs via Synergistic ERK Activation

Aims/Hypothesis: Diabetes with hypertension rapidly accelerates vascular disease, but the underlying mechanism remains unclear. We evaluated the hypothesis that the receptor of advanced glycation end products (RAGE) might mediate combined signals initiated by diabetes-related AGEs and hypertension-induced mechanical stress as a common molecular sensor. Methods: In vivo surgical vein grafts created by grafting vena cava segments from C57BL/6J mice into the common carotid arteries of streptozotocin (STZ)-treated and untreated isogenic mice for 4 and 8 weeks were analyzed using morphometric and immunohistochemical techniques. In vitro quiescent mouse vascular smooth muscle cells (VSMCs) with either knockdown or overexpression of RAGE were subjected to cyclic stretching with or without AGEs. Extracellular signalregulated kinase (ERK) phosphorylation and Ki-67 expression were investigated. Results: Significant increases in neointimal formation, AGE deposition, Ki-67 expression, and RAGE were observed in the vein grafts of STZ-induced diabetic mice. The highest levels of ERK phosphorylation and Ki-67 expression in VSMCs were induced by simultaneous stretch stress and AGE exposure. The synergistic activation of ERKs and Ki-67 in VSMCs was significantly inhibited by siRNA-RAGE treatment and enhanced by over-expression of RAGE. Conclusion: RAGE may mediate synergistically increased ERK activation and VSMC proliferation induced by mechanica

Propagative Exfoliation of High Quality Graphene

通讯作者地址: Deng, SL (通讯作者) Xiamen Univ, Dept Chem, Coll Chem & Chem Engn, Xiamen 361005, Peoples R China. [email protected]; [email protected] quality graphene materials that readily disperse in water or organic solvents are needed to achieve some of the most ambitious applications. However, current synthetic approaches are typically limited by irreversible structural damages, little solubility, or low scalability. Here, we describe a fundamental study of graphene chemistry and covalent functionalization patterns on sp(2) carbon lattices, from which a facile, scalable synthesis of high quality graphene sheets was developed. Graphite materials were efficiently exfoliated by reductive, propagative alkylation. The exfoliated, propagatively alkylated graphene sheets (PAGenes) not only exhibited high solubility in common solvents such as chloroform, water, and N-methyl-pyrrolidone, but also showed electrical conductivity as high as 4.1 X 10(3) S/m, which is 5 orders of magnitude greater than those of graphene oxides. Bright blue photoluminescence, unattainable in graphene, was also observed. We attribute the rise of blue photoluminescence in PAGenes to small on-graphene sp(2) domains created by the propagative covalent chemistry, which may expand from graphene edges or existing defect sites leaving sp(2)-hybridized patches interlaced with sp(3)-hybridized regions. The intact sp(2) domains enable effective electrical percolation among different graphene layers affording the observed high electrical conductivity in PAGene films.National Key Basic Research Program of China 2013CB933901 National Natural Science Foundation of China 21171140 21021061 21031004 U1205111 Natural Science Foundation of Fujian Province of China 2013J01056 Fundamental Research Funds for the Central Universities University of Maryland U.S. National Science Foundation CAREER CHE-105551

Propagative Exfoliation of High Quality Graphene

High quality graphene materials that readily disperse in water or organic solvents are needed to achieve some of the most ambitious applications. However, current synthetic approaches are typically limited by irreversible structural damages, little solubility, or low scalability. Here, we describe a fundamental study of graphene chemistry and covalent functionalization patterns on sp² carbon lattices, from which a facile, scalable synthesis of high quality graphene sheets was developed. Graphite materials were efficiently exfoliated by reductive, propagative alkylation. The exfoliated, propagatively alkylated graphene sheets (PAGenes) not only exhibited high solubility in common solvents such as chloroform, water, and <i>N</i>-methyl-pyrrolidone, but also showed electrical conductivity as high as 4.1 × 10³ S/m, which is 5 orders of magnitude greater than those of graphene oxides. Bright blue photoluminescence, unattainable in graphene, was also observed. We attribute the rise of blue photoluminescence in PAGenes to small on-graphene sp² domains created by the propagative covalent chemistry, which may expand from graphene edges or existing defect sites leaving sp²-hybridized patches interlaced with sp³-hybridized regions. The intact sp² domains enable effective electrical percolation among different graphene layers affording the observed high electrical conductivity in PAGene films

Effect of RAGE on VSMC proliferation (Ki-67 expression) induced by treatment of cyclic strain stress and/or AGEs.

<p>Cultured VSMCs were transfected by siRNA-RAGE (SiR) (Figures 6A-c, f, i, and l), siRNA control (SiC) (Figures 6A-b, e, h, and k) or Lipofectamine 2000 (LIP) (Figures 6A-a, d, g, and j) for 24 hours. They were then serum-starved for an additional 48 hours and treated with AGEs (Figures 6A-d, e, and f), cyclic stretch stress (SS) (Figures 6A-g, h, and i), or both (Figures 6A-j, k, and l) for 1 hour and cultured for another 24 hours. Figures 6A-a, b, and c show the negative control (NC). The cells were stained with primary Ki-67 antibody and TRITC-conjugated (red) secondary antibody and counterstained with DAPI (blue). The red symbols indicate Ki-67 antigens, while the blue symbols indicate the nuclei of the VSMCs. Bar = 50 µm. Figure 6B shows a statistical graph of ratio of Ki-67-positive cells from three independent experiments. *P<0.05 <i>versus</i> individual NC without stimulation of AGE and/or SS; #P<0.05 <i>versus</i> individual treatment in AGE or SS groups; a, b, and c P<0.05 <i>versus</i> SiC within a given group.</p

Identification of AGEs in serum (spectroscopic analysis) and vein grafts.

<p>Blood from the left atria of nondiabetic (Figure 3A-3) and diabetic (Figure 3A-4) mice was collected and the sera were separated for analysis of the characteristic fluorescence intensity pike of AGEs via spectroscopy. Dialyzed AGE-BSA came from bovine serum albumin (BSA) via incubation with high concentrations of glucose (0.5 M) for 8 weeks was used as a positive control (Figure 3A-5). PBS (Figure 3A-1) and BSA (Figure 3A-2) were used as negative controls. The characteristic fluorescence intensity pikes of AGEs in the diabetic serum were more than 2-fold relative to those observed in nondiabetic serum. Paraffin-embedded sections of the vein grafts from non-diabetic (Figures 3B-ND4w and 3D-ND8w) and diabetic (Figures 3C-D4w and 3E-D8w) mice killed 4 (Figures 3B-ND4w and 3C-D4w) and 8 (Figures 3D-ND8w and 3E-D8w) weeks after surgery were stained with primary AGE antibody and HRP-conjugated (brown) secondary antibody and counterstained with hematoxylin (blue). Significant AGE deposits (brown) were observed in the vein grafts of diabetic mice (Figures 3C-D4w and 3E-D8w). There were few brown deposits in the vein grafts of nondiabetic mice (Figures 3B-ND4w and 3D-ND8w). Bar = 50 µm.</p

Effects of siRNA-RAGE and RAGE overexpression on the activation of ERK1/2 in VSMCs induced by stretch stress and AGE incubation.

<p>Panel A: Cultured VSMCs transfected by siRNA-RAGE (SiR) for 24 hours and then serum-starved for additional 48 hours were harvested. A siRNA-control (SiC) was used as a negative control. Graph E shows statistical results of RAGE expression from three independent experiments. *P<0.05 <i>versus</i> SiC. The siRNA-pretreated VSMCs were treated with AGE (Panel B) or cyclic stretch stress (SS) (Panel C) or both (Panel D) for 10 minutes. They were then harvested for detection of ERK phosphorylation levels. Graphs F, G, and H show the statistical results of phosphorylated-ERK (pERK) levels from three independent experiments. (I) Cells stably overexpressing RAGE were subjected to the same treatment and corresponding pERK was detected (Panel K). Graph L shows the statistical results of pERK levels of Panel K from three independent experiments.. *P<0.05 versus individual negative control (NC) without stimulation by AGE and/or SS; #P<0.05 versus SiC or vector within a given group. LIP represents Lipofectamine 2000. V represents cells transfected with empty vectors. R-F represents cells stably overexpressing full-length RAGE.</p

Representative photomicrograph of HE-stained sections of mouse control veins and vein grafts.

<p>Under anesthesia, the vena cava segments of mice were grafted into the carotid arteries of (A, C, E) nondiabetic and (B, D, F) diabetic mice. Animals were killed (A, B) 0, (C, D) 4, and (E, F) 8 weeks after surgery, and the grafted veins were fixed in 4% phosphate-buffered (pH 7.2) formaldehyde, embedded in paraffin, sectioned, and stained with HE. Arrowheads and stars indicate the wall thickness and lumens, respectively, of the (A, B) control vessel and (C–F) vein grafts. G shows statistical graphs of wall thickness of vein grafts of different groups (0, 4, and 8 weeks after operation). *P<0.05 <i>versus</i> normal control of ND mice, #P<0.05 <i>versus</i> time-matched ND groups. Bar = 50 µm.</p

Role of the RAGE signal pathway in the synergistic effects of cyclic stretch stress and AGEs on ERK activation and proliferation in VSMCs.

<p>Increased blood pressure can trigger rapid increases in mechanical stretching on the walls of vein grafts. Stretch stress causes deformation of the vascular cells (VSMCs) and non-specifically activates RAGE and its downstream signal molecules, such as ERK, leading to over-proliferation (Ki-67 expression) of the vascular cells. Hyperglycemia can produce numerous AGEs. These modified proteins are deposited on the vascular wall, where they directly and specifically interact with RAGE and activate intracellular signaling molecules, altering vascular structure and function. Blocking RAGE and its downstream molecules may inhibit the synergistically accelerated vascular remodeling induced by hypertension-stretch stress with and without AGEs. Further investigations may provide new targets for drug development and new strategies for the treatment and prevention of vascular diseases, such as atherosclerosis, in diabetic patients.</p