Capturing the Direct Binding of CFTR Correctors to CFTR by Using Click Chemistry

Cystic fibrosis (CF) is a lethal genetic disease caused by the loss or dysfunction of the CF transmembrane conductance regulator (CFTR) channel. F508del is the most prevalent mutation of the CFTR gene and encodes a protein defective in folding and processing. VX‐809 has been reported to facilitate the folding and trafficking of F508del‐CFTR and augment its channel function. The mechanism of action of VX‐809 has been poorly understood. In this study, we sought to answer a fundamental question underlying the mechanism of VX‐809: does it bind CFTR directly in order to exert its action? We synthesized two VX‐809 derivatives, ALK‐809 and SUL‐809, that possess an alkyne group and retain the rescue capacity of VX‐809. By using Cu^I‐catalyzed click chemistry, we provide evidence that the VX‐809 derivatives bind CFTR directly in vitro and in cells. Our findings will contribute to the elucidation of the mechanism of action of CFTR correctors and the design of more potent therapeutics to combat CF.     

Comparison of hydrogen isotope retention and irradiation damage behaviors in tungsten and SS-316 with simultaneous C+–D2+ implantation

Behaviors of hydrogen isotope retention and damages in tungsten and SS-316 with simultaneous C⁺–D₂⁺ implantation were compared to those with only D₂⁺ implantation using X-ray photoelectron spectroscopy (XPS), Thermal desorption spectroscopy (TDS), glow discharge-optical emission spectroscopy (GD-OES) and Transmission electron microscopy (TEM).The total D retention for SS-316 with only D₂⁺ implantation was about 45% as large as that for tungsten. The D retention for simultaneous C⁺–D₂⁺ implanted tungsten and SS-316 clearly increased as a factor of 1.7, which is almost the same among these samples. The density of dislocation loops was enhanced by the simultaneous C⁺–D₂⁺ implantation, indicating the D trapping site would be produced by C⁺ implantation. As for the D desorption temperature, small shift toward lower temperature side was found for SS-316 compared to tungsten, indicating the D trapping energy by dislocation loops and grain boundary for SS-316 is lower than that for tungsten.     

Properties of gas (CO2) microbubbles made by hand agitation and it's contrast enhancing effect

The property of gas (CO2) microbubbles made by hand agitation and it's contrast enhancing effect of abdominal organs on gray scale ultrasound are here described. The size of microbubbles of CO2 gas adequately prepared with 5% human serum albumin was nearly 23 microns in mean diameter. However, the size and the density of gas microbubbles are affected with many factors, including mixing times, volume ratio of gas and liquid and the species of gas and liquid. On the other hand, contrast enhancing effect is determined by the size and the density of gas microbubbles. For the adequate evaluation of contrast enhancing effect of abdominal tumors by enhanced ultrasonography, the property of gas microbubbles described as above should be carefully considered.     

A high-speed-retry banyan switch architecture for giga-bit-rate BISDN networks

This paper proposes a high-speed ATM switch architecture for handling cell rates of several Gb/s in a broadband communication switching system or cross-connect system. The proposed switch architecture, named the high-speed-retry banyan switch, employs a bufferless banyan network between input and output buffers; a cell is repeatedly transmitted from an input buffer until it can be successfully transmitted to the desired output buffer. A simple cell-retransmission algorithm, is employed as is a ring-arbitration algorithm for cell conflict. They are suitable for FIFO type buffers and bufferless highspeed devices. Good traffic characteristics which are independent of switch size are achieved for an internal speed ratio of only four times the input line speed. A prototype system with the internal speed of 1·2 Gb/s is constructed in order to confirm the basic operation of the high-speed-retry banyan switch. The prototype system, even in its present state, could be used to realize a giga-bit-rate BISDN switching system.     

Hydrothermal synthesis and electrochemical behavior of orthorhombic LiMnO2

The most highlighted point of this work to emphasize is that it is the first trial to use Mn₃O₄ oxide as a precursor to synthesize orthorhombic LiMnO₂ by the hydrothermal method. A well-ordered orthorhombic LiMnO₂ phase was formed by the hydrothermal treatment of Mn₃O₄ with excess LiOH aqueous solution at 170 °C. According to TEM observation, the as-synthesized powder was single crystalline particle oxide. Comparing with other orthorhombic LiMnO₂ prepared by low temperature synthetic route and by high temperature calcination, the orthorhombic LiMnO₂ prepared by the hydrothermal route showed enhanced battery performance as a lithium battery cathode material. We believe that the new hydrothermal synthesis is expected as an excellent alternative of powder preparation method of high capacity cathode material to be used for Li-ion secondary battery.     

Enumeration and identification of Campylobacter species in the liver and bile of slaughtered cattle

Healthy cattle are considered as reservoirs for a variety of Campylobacter species. To control the bacterial contamination in meat products, quantitative assessment of campylobacters in liver and gallbladder was carried out at an abattoir. Liver and bile samples were collected from 108 healthy beef cattle after evisceration and viable counts of campylobacters were determined by a direct-plating technique using modified Cefoperazone Charcoal Deoxycholate agar (mCCDA). The suspected colonies on the highest dilution plates were subjected to biochemical tests and PCR for identification. Campylobacter species were isolated from 49 (45%) bile and 6 (5%) liver specimens examined. Numbers of campylobacters in bile and liver ranged from log(10)3 to 7 (median 5) and log(10) 1 to 2 (median 1) cfu per ml and per g, respectively. These Campylobacter species were identified as C. fetus, C. jejuni, and C. coli. Multiple infections involving two species were observed in 16 cattle. C. fetus and C. jejuni were the predominant species in bile. Growth of C. fetus, C. jejuni, and C. coli in spiked bile samples revealed an initial exponential growth phase followed by a period with no apparent increase in colony count for 28 days. It appeared that these campylobacters can survive in bile for a long period. To determine transfer route of bacterial cells to the gallbladder, C. jejuni, C. fetus, or C. coli was inoculated intravenously in mice. The inoculated cells were recovered from bile, suggesting that the organism was transferred from the blood stream to bile duct in the liver. From these results, bile in cattle is considered to be an important contamination source of Campylobacter species in processing plants.     

Synthesis and electrochemical properties of lithium non-stoichiometric Li1+x(Ni1/3Co1/3Mn1/3)O2+δ prepared by a spray drying method

Lithium non-stoichiometric Li[Li_x(Ni_1/3Co_1/3Mn_1/3)_1−x]O₂ materials (0 ≤ x ≤ 0.17) were synthesized using a spray drying method. The electrochemical properties and structural stabilities of the synthesized materials were investigated. The synthesized materials exhibited a hexagonal structure in all the x-value and the lattice parameters of the materials were gradually decreased with increasing x-value due to an increasing amount of Ni³⁺ ions for charge compensation. The capacity retention ability and rate capability of the stoichiometric Li(Ni_1/3Co_1/3Mn_1/3)O₂ material were improved by increasing x-value, the so-called overlithiation. We found that the overlithiated materials could keep more structural integrity than the stoichiometric one during electrochemical cyclings, which could be one of reasons for a better electrochemical properties of the overlithiated materials.     

Rural–urban migration and multinational firms

In this paper, we re-examine the analysis on multinational firms and the theory of international trade and investment in the set-up with urban unemployment. A great majority of the recipient (host) countries are developing economies that are characterized by rural–urban migration in the face of urban unemployment. Thus, they have relatively developed urban sectors and less developed rural sectors. In this context we explore the implications of tariffs and taxes on the urban unemployment rate and national income.     

Power packet dispatching with second‐order clock synchronization

Aiming to distinguish sources and loads for the rapid scaling of renewable power sources, a novel power packet dispatching system has been proposed with a structure similar to those of communication systems. Accurate clock synchronization is necessary to achieve the exchange of information attached in a power packet. At the same time, the clock synchronization is an interesting topic for developing power packet dispatching between multi‐sender and a receiver. This work outlines the implementation of second‐order autonomously controlled clock synchronization into the power packet dispatching system. At first, we derive the second‐order controlled model of a digital clock synchronization method and analyze the stability of the developed model. Secondly, through experiments, it is shown that the information of power packets can be recognized correctly and the power can be distributed to directed loads. This paper demonstrates the validity of the asynchronous power packet dispatching based on our derived model. Copyright © 2015 John Wiley & Sons, Ltd.