Diphenyl-Methane Based Thyromimetic Inhibitors for Transthyretin Amyloidosis

Thyromimetics, whose physicochemical characteristics are analog to thyroid hormones (THs) and their derivatives, are promising candidates as novel therapeutics for neurodegenerative and metabolic pathologies. In particular, sobetirome (GC-1), one of the initial halogen-free thyromimetics, and newly synthesized IS25 and TG68, with optimized ADME-Tox profile, have recently attracted attention owing to their superior therapeutic benefits, selectivity, and enhanced permeability. Here, we further explored the functional capabilities of these thyromimetics to inhibit transthyretin (TTR) amyloidosis. TTR is a homotetrameric transporter protein for THs, yet it is also responsible for severe amyloid fibril formation, which is facilitated by tetramer dissociation into non-native monomers. By combining nuclear magnetic resonance (NMR) spectroscopy, computational simulation, and biochemical assays, we found that GC-1 and newly designed diphenyl-methane-based thyromimetics, namely IS25 and TG68, are TTR stabilizers and efficient suppressors of TTR aggregation. Based on these observations, we propose the novel potential of thyromimetics as a multi-functional therapeutic molecule for TTR-related pathologies, including neurodegenerative diseases.     

Properties and applications of β‐glycosidase from Bacteroides thetaiotaomicron that specifically hydrolyses isoflavone glycosides

To modify the glycan part of glycosides, the gene encoding β‐glycosidase was cloned from Bacteroides thetaiotaomicron VPI‐5482. The cloned gene, bt_1780, was expressed in Escherichia coli MC1061 and the expressed enzyme was purified using Ni‐NTA affinity chromatography. The purified enzyme, BTBG, showed optimal activity at 50 °C and pH 5.5. Interestingly, this enzyme did not have any hydrolysing activity on ordinary β‐linkage–containing substrates such as xylobiose, lactose and cello‐oligosaccharide, but specifically hydrolysed isoflavone glycosides such as daidzin, genistin and glycitin. Compared to a commercial beta glucosidase, BTBG selectively hydrolysed isoflavone glycosides in soybean extract mixture solution. These results suggest that BTBG may be a specialized enzyme for the hydrolysis of glycosides and that the substrate specificity of BTBG is applicable for the bioconversion of isoflavone glycosides in the food industry.     

Effects of extended dislocations on charge distribution in GaN epilayer

We have investigated the effect of extended dislocations (0.5-3 μm) on charge distribution in GaN epilayer grown by metalorganic chemical vapor deposition on (0001) sapphire using atomic force microscopy (AFM) and scanning surface potential microscopy (SSPM). It has been observed for the surface at the extended dislocations present in undoped GaN film to be negatively charged showing 0.04-0.2 V higher potential relative to regions that contain no dislocations. In addition to the higher potential at the dislocation core, the surrounding surfaces, including the edge of the dislocations, are also negatively charged in a symmetric way around the dislocations revealing crater-shaped higher potential regions (∼0.04 V) relative to surrounding dislocation-free area. The experimental results show that the protrusion-type of dislocation is also negatively charged and its potential is dependent on the size of dislocation.     

A Critique of the ANSI Standard on Role-Based Access Control

In 2004, the American National Standards Institute approved the Role-Based Access Control standard to fulfill "a need among government and industry purchasers of information technology products for a consistent and uniform definition of role based access control (RBAC) features". Such uniform definitions give IT product vendors and customers a common and unambiguous terminology for RBAC features, which can lead to wider adoption of RBAC and increased productivity. However, the current ANSI RBAC Standard has several limitations, design flaws, and technical errors that, it unaddressed, could lead to confusions among IT product vendors and customers and to RBAC implementations with different semantics, thus defeating the standard's purpose.     

Strong Diffie-Hellman-DSA Key Exchange

To provide authentication to the Diffie-Hellman key exchange, a few integrated key exchange schemes which provide authentication using the DSA signature have been proposed in the literature. In this letter we point out that all of the previous Diffie-Hellman-DSA schemes do not provide security against session state reveal attacks. We also suggest a strong Diffie-Hellman-DSA scheme providing security against session state reveal attacks as well as forward secrecy and key independence     

A four-channel 3.125-Gb/s/ch CMOS serial-link transceiver with a mixed-mode adaptive equalizer

This work presents a quad-channel serial-link transceiver providing a maximum full duplex raw data rate of 12.5Gb/s for a single 10-Gbit eXtended Attachment Unit Interface (XAUI) in a standard 0.18-/spl mu/m CMOS technology. To achieve low bit-error rate (BER) and high-speed operation, a mixed-mode least-mean-square (LMS) adaptive equalizer and a low-jitter delay-immune clock data recovery (CDR) circuit are used. The transceiver achieves BER lower than <4.5/spl times/10/sup -15/ while its transmitted data and recovered clock have a low jitter of 46 and 64 ps in peak-to-peak, respectively. The chip consumes 178 mW per each channel at 3.125-Gb/s/ch full duplex (TX/RX simultaneous) data rate from 1.8-V power supply.     

Radiation-laminar free convection in a square duct with specular reflection by absorbing-emitting medium

The purpose of this work is to study the effects of specularly reflecting wall under the combined radiative and laminar free convective heat transfer in an infinite square duct. An absorbing and emitting gray medium is enclosed by the opaque and diffusely emitting walls. The walls may reflect diffusely or specularly. Boussinesq approximation is used for the buoyancy term. The radiative heat transfer is evaluated using the direct discrete ordinates method. The parameters under considerations are Rayleigh number, conduction to radiation parameter, optical thickness, wall emissivity and reflection mode. The differences caused by the reflection mode on the stream line, and temperature distribution and wall heat fluxes are studied. Some differences are observed for the categories mentioned above if the order of the conduction to radiation parameter is less than order of 10^-3 for the range of Rayleigh number studied. The differences at the side wall heat flux distributions are observed as long as the medium is optically thin. As the top wall emissivity decreases, the differences between these two modes are increased. As the optical thickness decreases at the fixed wall emissivity, the differences also increase. The difference of the streamlines or the temperature contours is not as distinct as the side wall heat flux distributions. The specular reflection may alter the fluid motion.     

New approach to enhance adhesions between carbon nanotube emitters and substrate by the combination of electrophoresis and successive electroplating

Complementary electroplating combined with electrophoresis enhanced the field emission characteristics of emitters by improving the adhesions between CNT emitters and substrate. The emitting current of the CNT emitters prepared by our combined method increased nine times higher than that of CNT emitters prepared by electrophoresis only, since electroplating improved the adhesion of CNT emitters. During the life-time measurement for 10 h, the emitting current of CNT emitters fabricated by electrophoresis only was drastically decreased to 13% of the initial current, while that prepared by the combination of electrophoresis and successive electroplating decreased to 64% of the initial current. We suggest that our method is a promising approach for the efficient fabrication of reliable CNT emitters.