Silicon-Nanotube-Mediated Intracellular Delivery Enables Ex Vivo Gene Editing

Engineered nano–bio cellular interfaces driven by vertical nanostructured materials are set to spur transformative progress in modulating cellular processes and interrogations. In particular, the intracellular delivery—a core concept in fundamental and translational biomedical research—holds great promise for developing novel cell therapies based on gene modification. This study demonstrates the development of a mechanotransfection platform comprising vertically aligned silicon nanotube (VA-SiNT) arrays for ex vivo gene editing. The internal hollow structure of SiNTs allows effective loading of various biomolecule cargoes; and SiNTs mediate delivery of those cargoes into GPE86 mouse embryonic fibroblasts without compromising their viability. Focused ion beam scanning electron microscopy (FIB-SEM) and confocal microscopy results demonstrate localized membrane invaginations and accumulation of caveolin-1 at the cell–NT interface, suggesting the presence of endocytic pits. Small-molecule inhibition of endocytosis suggests that active endocytic process plays a role in the intracellular delivery of cargo from SiNTs. SiNT-mediated siRNA intracellular delivery shows the capacity to reduce expression levels of F-actin binding protein (Triobp) and alter the cellular morphology of GPE86. Finally, the successful delivery of Cas9 ribonucleoprotein (RNP) to specifically target mouse Hprt gene is achieved. This NT-enhanced molecular delivery platform has strong potential to support gene editing technologies.     

The life evaluation by linear cumulative damage rule for cold dwell fatigue of Ti-6Al-4V alloy

Low cycle fatigue (LCF) life at ambient temperature of Ti alloys is well known to decrease with stress dwell. This phenomenon, called cold dwell fatigue (CDF), is influenced by the peak stress, dwell time, and microstructure. For this study, the CDF life was evaluated by the linear cumulative damage rule. The influence of test conditions and microstructure on the linear cumulative damage rule was also verified. By the linear cumulative damage rule, when creep damage is calculated using the time exhaustion rule, theCDF damage was evaluated by the inequality of D_Total = (D_F, D_C) ≤ (0.01, 10^?6). However, the CDF damage can be evaluated in the range of D_Total = 0.6–1.2 when creep damage was calculated using the ductile exhaustion rule. Results indicate that the evaluation was almost independent of the dwell time, peak stress, and microstructure, so it is also a versatile method for evaluating CDF responses.     

Application of ER gel with variable friction surface to the clamp system of aerostatic slider

An electro-rheological fluid (ERF) is a functional fluid whose viscoelastic properties vary according to the intensity of the applied electric field. ERFs are mixtures of nonconductive silicone oil and inorganic/organic composite electro-rheological particles. The properties of ERFs have been exploited to control the performance of machine elements. ERFs have been applied to machine elements such as variable dampers and clutches. However, ERFs have disadvantages, namely the sedimentation of ER particles and the requirement of a seal mechanism. The sedimentation of ER particles reduces the ER effects and results in low stability of ER devices. In order to suppress the sedimentation, and thereby improve the performance of ERF devices, a new functional material called the gel-structured ERF (ERG) is developed, whose basic properties are analyzed in this study. The ER particles are suspended in the gel component, and thus will not precipitate out. This suppresses the decrease in the ER effect caused by precipitation. The ERG developed shows a large shear stress variation in response to the applied electric field. This high performance of ERG originates in a mechanism different from the ER effects of ERF. In order to elucidate the mechanism in ERG, the behavior of ER particles was observed under an electric field. The results show that the contact conditions at the interface between electrode and ERG change rapidly in response to the applied electric field, which result in a variation in shear force. On the basis of the results of a preliminary analysis, ERG was applied to the precision clamp system of an aerostatic slider, and its performance was assessed experimentally.     

形状记忆合金的动态加热控制方法研究

由于环境温度、热对流和热辐射条件以及输入的加热电流强度的不同，致使嵌在复合材料中的形状记忆合金的温度难以确定。为了在最短时间促成形状记忆合金的相变并防止因过热而烧毁复合材料或形状记忆合金驱动元件，提出了一种基于电阻变化率反馈的动态自传感加热方法，它可以实时监测相变的起始点和结束点，有效地防止过热。试验结果与理论分析吻合良好。     

Real-Time Determination of Absolute Frequency in Continuous-Wave Terahertz Radiation with a Photocarrier Terahertz Frequency Comb Induced by an Unstabilized Femtosecond Laser

A practical method for the absolute frequency measurement of continuous-wave terahertz (CW-THz) radiation uses a photocarrier terahertz frequency comb (PC-THz comb) because of its ability to realize real-time, precise measurement without the need for cryogenic cooling. However, the requirement for precise stabilization of the repetition frequency (f _rep) and/or use of dual femtosecond lasers hinders its practical use. In this article, based on the fact that an equal interval between PC-THz comb modes is always maintained regardless of the fluctuation in f _rep, the PC-THz comb induced by an unstabilized laser was used to determine the absolute frequency f _THz of CW-THz radiation. Using an f _rep-free-running PC-THz comb, the f _THz of the frequency-fixed or frequency-fluctuated active frequency multiplier chain CW-THz source was determined at a measurement rate of 10 Hz with a relative accuracy of 8.2?×?10^?13 and a relative precision of 8.8?×?10^?12 to a rubidium frequency standard. Furthermore, f _THz was correctly determined even when fluctuating over a range of 20 GHz. The proposed method enables the use of any commercial femtosecond laser for the absolute frequency measurement of CW-THz radiation.     

Review Paper: Multi‐primary‐color displays: The latest technologies and their benefits

Abstract— Multi‐primary‐color (MPC) display technology is one of the fastest emerging research areas in recent years. Wide‐color‐gamut display devices have been required for visually sufficient and/or accurate color reproduction. It is well known that MPC displays can reproduce accurate colors with high efficiency. In addition, not only the image‐quality improvement but some other performance of display devices is also required for display devices. This paper reviews achievements in MPC display technologies and focuses on the benefits of MPC displays: power‐savings and high resolution.     

Intravital dual-colored visualization of colorectal liver metastasis in living mice using two photon laser scanning microscopy

A major challenge of cancer biology is to visualize the dynamics of the metastatic process in secondary organs at high optical resolution in vivo real-time. Here, we presented intravital, dual-colored imaging of liver metastasis formation from a single cancer cell to metastatic colonies in the living liver of living mice using two photon laser scanning microscopy (TPLSM). Red fluorescent protein expressing murine (SL4) or human (HT29) colorectal cancer cell lines were inoculated to the spleen of green fluorescent protein expressing mice. Intravital TPLSM was performed by exteriorizing and fixing the liver lobe of living mice. This was repeated several times for the long-term imaging of the same mouse. Viable cancer cells in the living liver of living mice were visualized intravitally at a magnification of over 600×. Single cancer cells were arrested within hepatic sinusoids 2 h after injection. Platelet aggregation surrounding a cancer cell was observed, indicating a phenomenon of tumor-cell induced platelet aggregation. Cancer cells were extravasated from hepatic sinusoids to the space of Disse. Protrusions of Kupffer cells surrounding a cancer cell were observed, indicating that Kupffer cells appear to phagocytose cancer cells. SL4 cells formed liver metastatic colonies with extensive stromal reaction. Liver metastases by HT29 cells were observed as a cluster of micrometastatic nodules. High-resolution, dual-colored, real-time visualization of cancer metastasis using intravital TLPSM can help to understand spatiotemporal tumor-host interactions during metastatic processes in the living organs of living animals.     

Optimized Stoneley wave device by proper choice of glass overcoat

The characteristics of a Stoneley wave propagated along an interface between a piezoelectric material and an isotropic material were investigated both theoretically and experimentally. First, the condition for the existence of Stoneley waves was shown for various piezoelectric materials. A rule of thumb for selecting the combination of the two materials was obtained. Then, LiTaO₃ was selected as the piezoelectric material and SiO₂ was selected the isotropic material. After the calculation of the Stoneley wave characteristics, actual devices were fabricated and measured. The experimental results were found to be in good agreement with the theory; zero slope temperature and high electromechanical coupling coefficient ( K²=1.5%) were obtained for Stoneley wave propagation between SiO₂/X-148° LiTaO₃. As a result, future surface-acoustic-wave (SAW) devices can be made without any package     

Field performance of an energy pile system for space heating

This paper describes the field performance of air conditioning with an energy pile system, which was applied to the pile foundations of an actual building for the purpose of reducing the cost of the underground heat exchanger. First, the building for both office and residential use, for which a space heating and cooling system using friction piles was installed, was built in Sapporo in December 2000. Second, three tests were carried out to specify the design of a heat exchanger inside the pile, and a U-tube type underground heat exchanger was adopted from the viewpoint of energy efficiency and installation costs. Long-term space heating operation measurements indicated that the seasonal average temperatures of brine returning from the underground and pile surfaces were 2.4 and 6.7 °C, respectively. The average coefficient of performance for space heating was quite high at 3.9, and the seasonal primary energy reduction rate compared with a typical air conditioning system reached 23.2%.     

The effect of crystal textures on the anodic oxidization of zirconium in a boiling nitric acid solution

The effects of crystal textures and the potentials in the anodic oxidation of zirconium in a boiling nitric acid solution were investigated to study the stress corrosion cracking of zirconium in nitric acid solutions. The test specimen was machined such that the specimen surface was parallel to the rolling surface, arranged with a (0002) crystal texture. The potentials applied for the anodic oxidation of zirconium were set at 1.2, 1.4, and 1.5 V against a saturated KCl–Ag/AgCl electrode (SSE) in boiling 6 M HNO₃. The growth of the zirconium oxide film dramatically changed depending on the applied potential at a closed depassivation potential (1.47 V vs. SSE in this study). At 1.5 V, the zirconium oxide film rapidly grows, and its growth exhibits cyclic oxidation kinetics in accordance with a nearly cubic rate law. The zirconium oxide film grows according to the quantity of electric charge and the growth rate does not depend on the crystal texture in the pretransition region before the cyclic oxidation kinetics. However, the growth and cracking under the thick oxide film depend on the crystal texture in the transition region. On the normal direction side, the oxide film thickness decreases on average since some areas of the thick oxide film are separated from the specimen surface owing to the cracks in the thick oxide. On the rolling direction (RD) side, no cracks in the thick oxide film are observed, but cracks are found under the thick oxide film, which deeply propagate in metal matrix along the RD without an external stress. The cracks under the thick oxide film propagate to the center of the oxide layer. The crystal orientation relationship between the oxide layer and the zirconium matrix is (0002)_Zr//(111)_ZrO2, and the cracks in the oxide layer propagate in the (0002)_Zr plane in the zirconium matrix. The oxide layer consists of string-like zirconium oxide and zirconium hydride. The string-like zirconium oxide contains orthorhombic ZrO₂ in addition to monoclinic ZrO₂. It is not well known why the cracks propagate along the (0002)_Zr plane under the thick oxide film. As one assumption for the mechanism of crack initiation and propagation without an external stress, it is considered that the oxidizing zirconium hydrides precipitated in the (0002)_Zr plane near the interface of the thick oxide film and the matrix. Then, the phase transformation from orthorhombic ZrO₂ to monoclinic ZrO₂ in the oxide layer causes the crack propagation in the (0002) plane.