Antisense Oligonucleotide Modified with Disulfide Units Induces Efficient Exon Skipping in mdx Myotubes through Enhanced Membrane Permeability and Nucleus Internalization

We have found that antisense oligonucleotides and siRNA molecules modified with repeat structures of disulfide units can be directly introduced into the cytoplasm and exhibit a suppressive effect on gene expression. In this study, we analyzed the mechanism of cellular uptake of these membrane-permeable oligonucleotides (MPONs). Time-course analysis by confocal microscopy showed that the uptake of MPONs from the plasma membrane to the cytoplasm reached 50 % of the total uptake in about 5 min. In addition, analysis of the plasma membrane proteins to which MPONs bind, identified several proteins, including voltage-dependent anion channel. Next, we analyzed the behavior of MPONs in the cell and found them to be abundant in the nucleus as early as 24 h after addition with the amount increasing further after 48 and 72 h. The amount of MPONs was 2.5-fold higher than that of unmodified oligonucleotides in the nucleus after 72 h. We also designed antisense oligonucleotides and evaluated the effect of MPONs on mRNA exon skipping using DMD model cells; MPONs caused exon skipping with 69 % efficiency after 72 h, which was three times higher than the rate of the control. In summary, the high capacity for intracytoplasmic and nuclear translocation of MPONs is expected to be useful for therapeutic strategies targeting exon skipping.     

Completely Chemically Synthesized Long DNA Can be Transcribed in Human Cells

Chemical ligation reaction of DNA is useful for the construction of long functional DNA using oligonucleotide fragments that are prepared by solid phase chemical synthesis. However, the unnatural linkage structure formed by the ligation reaction generally impairs the biological function of the resulting ligated DNA. We achieved the complete chemical synthesis of 78 and 258 bp synthetic DNAs via multiple chemical ligation reactions with phosphorothioate and haloacyl-modified DNA fragments. The latter synthetic DNA, coding shRNA for luciferase genes with a designed truncated SV promoter sequence, successfully induced the expected gene silencing effect in HeLa cells.     

A method for estimating the errors in many-light rendering with supersampling

Computational Visual Media - In many-light rendering, a variety of visual and illumination effects, including anti-aliasing, depth of field, volumetric scattering, and subsurface scattering, are...     

Virtual Society: Collaboration in 3D Spaces on the Internet

The Virtual Society (VS) project is a long term research initiativethat is investigating the evolution of the futureelectronic society. Our vision for this electronic societyis a shared 3D virtual world where users, from homes and offices, canexplore, interact and work. Our first implementation of aninfrastructure to support our investigation is known asCommunityPlace and has been developed to support large-scale shared 3D spaces onthe Internet using the Virtual Reality Modeling Language (VRML). Obviously, such an ambitious project cutsacross many different domains. In this paper we outline thegoals of the Virtual Society project, discuss the architecture andimplementation of CommunityPlace with particular emphasis on Internetrelated technologies such as VRML and present our views on the role ofVRML and the Internet to support large-scale shared 3D spaces.     

Crowdsourced idea generation: The effect of exposure to an original idea

Crowdsourcing is an increasingly important approach to pursuing innovation. In crowdsourcing ideation websites, crowd members are often exposed to some stimulus ideas, such as examples provided by companies or peers' ideas. Understanding the effect of being exposed to original stimulus ideas in this context may inform the design of the crowdsourcing process. To test this effect, an experiment was conducted where crowd workers were asked to design a public service advertisement. Depending on the experimental condition, the participants were exposed to an original idea, or a common idea, or no idea. As compared to the absence of exposure, exposure to an original idea decreased fluency, defined as the number of ideas generated by each person, and increased the average originality of ideas generated by each person. By contrast, exposure to a common idea had no effect on either idea originality or fluency. The semantic similarity between the stimulus idea and the first idea generated was higher when the stimulus was common versus original as measured by latent semantic analysis. The implications of these results for research and practice are discussed.     

A novel low‐power gate driver architecture for large 8 K 120 Hz liquid crystal display employing IGZO technology

A novel low‐power gate driver architecture was developed for large 8 K 120 Hz liquid crystal display panel. For this application, not only high‐speed driving but also low power consumption is required. We employed a high mobility In‐Ga‐Zn‐O, dual V_GL level driving method, and gate driver circuit driven by DC supply. The simulation results show that our proposals meet 8 K 120 Hz driving requirements. Also, we have fabricated a prototype panel and confirmed both high‐speed driving and low power consumption.     

Effect of silicate incorporation on in vivo responses of α-tricalcium phosphate ceramics

In addition to calcium phosphate-based ceramics, glass-based materials have been utilized as bone substitutes, and silicate in these materials has been suggested to contribute to their ability to stimulate bone repair. In this study, a silicate-containing α-tricalcium phosphate (α-TCP) ceramic was prepared using a wet chemical process. Porous granules composed of silicate-containing α-TCP, for which the starting composition had a molar ratio of 0.05 for Si/(P + Si), and silicate-free α-TCP were prepared and evaluated in vivo. When implanted into bone defects that were created in rat femurs, α-TCP ceramics either with or without silicate were biodegraded, generating a hybrid tissue composed of residual ceramic granules and newly formed bone, which had a tissue architecture similar to physiological trabecular structures, and aided regeneration of the bone defects. Supplementation with silicate significantly promoted osteogenesis and delayed biodegradation of α-TCP. These results suggest that silicate-containing α-TCP is advantageous for initial skeletal fixation and wound regeneration in bone repair.     

A character art generator using the local exhaustive search,with GPU acceleration

An ASCII art is a matrix of ASCII code characters that reproduces an original grey-scale image. A JIS art is an ASCII art that uses JIS Kanji code characters instead of ASCII code characters. They are commonly used to represent pseudo grey-scale images in text -based messages. Since automatic generation of high quality ASCII/JIS art images is very hard, they are usually produced by hand. The main contribution of this paper is to propose a new technique to generate an ASCII/JIS art that reproduces the original tone and the details of an input grey-scale image. Our new technique is inspired by the local exhaustive search (LES) to optimise binary images for printing based on the characteristic of the human visual system. Although it can generate high quality ASCII/JIS art images, a lot of computing time is necessary for the LES. Hence, we have implemented our new technique in a graphics processing unit (GPU) to accelerate the computation. The experimental results show that the GPU implementation can achieve a speedup factor up to 89.56 over the conventional CPU implementation.     

Segregation Behavior Found in Poly(2-ethylhexyl acrylate)/Poly-(vinylidenefluoride-co-hexafluoro acetone) Blends

The surface and bottom compositions of poly(2-ethylhexyl acrylate) (P2EHA)/poly-(vinylidene fluoride-co-hexafluoro acetone) [P(VDF-HFA)] blends were investigated by XPS analysis. In these blends, the enriched P(VDF-HFA) layer was observed from the top surface to a few nm depth, while the P2EHA component segregated at the bottom (the surface in contact with release liner). The probe tack values of the bottom side were remarkably larger than those of the surface side for the P2EHA/P(VDF-HFA) blends because the characteristic segregation structure was formed. We expected that the P2EHA/P(VDF-HFA) blends could be utilized as a non-backing pressure sensitive adhesive (PSA) tape. The effects of the film thickness of the blends and the molecular weights of P2EHA on the segregation structure were also examined. We thought that segregation behavior found in P2EHA/P(VDF-HFA) blends was caused by several factors, such as surface tension, miscibility, density, and rate of solvent casting.