Activation of AMP-activated protein kinase (AMPK) through inhibiting interaction with prohibitins.

5'-Adenosine monophosphate-activated protein kinase (AMPK) is a potential therapeutic target for various medical conditions. We here identify a small-molecule compound (RX-375) that activates AMPK and inhibits fatty acid synthesis in cultured human hepatocytes. RX-375 does not bind to AMPK but interacts with prohibitins (PHB1 and PHB2), which were found to form a complex with AMPK. RX-375 induced dissociation of this complex, and PHBs knockdown resulted in AMPK activation, in the cultured cells. Administration of RX-375 to obese mice activated AMPK and ameliorated steatosis in the liver. High-throughput screening based on disruption of the AMPK-PHB interaction identified a second small-molecule compound that activates AMPK, confirming the importance of this interaction in the regulation of AMPK. Our results thus indicate that PHBs are previously unrecognized negative regulators of AMPK, and that compounds that prevent the AMPK-PHB interaction constitute a class of AMPK activator.

Room-temperature magnetoresistance in Ni78Fe22/C8-BTBT/Ni78Fe22 nanojunctions fabricated from magnetic thin-film edges using a novel technique.

Molecular spintronic devices are gaining popularity because the organic semiconductors with long spin relaxation times are expected to have long spin diffusion lengths. A typical molecular spintronic device consists of organic molecules sandwiched between two magnetic layers, which exhibits magnetoresistance (MR) effect. Nanosized devices are also expected to have a high spin polarization, leading to a large MR effect owing to effective orbital hybridization. However, most studies on nanosized molecular spintronic devices have investigated the MR effect at low temperatures because of the difficulty in observing the MR effect at room temperature. Here we focus on high-mobility molecules expected to show long spin diffusion lengths, which lead to the observation of the MR effect in nanoscale junctions at room temperature. In this study, we fabricate magnetic nanojunctions consisting of high-mobility molecules, 2,7-dioctyl[1]benzothieno[3,2-b][1]benzothiophene (C8-BTBT), sandwiched between two Ni78Fe22 thin films with crossed edges. Transmission electron microscopy (TEM) images reveal that C8-BTBT molecular layers with smooth and clear interfaces can be deposited on the Ni78Fe22 thin-film edges. Consequently, we observe a clear positive MR effect, that is, R P < R AP, where R P and R AP are the resistances in the parallel (P) and antiparallel (AP) configurations, respectively, of two magnetic electrodes in the Ni78Fe22/C8-BTBT/Ni78Fe22 nanojunctions at room temperature. The obtained results indicate that the spin signal through the C8-BTBT molecules can be successfully observed. The study presented herein provides a novel nanofabrication technique and opens up new opportunities for research in high-mobility molecular nano-spintronics.

A Novel Technique for Controlling Anisotropic Ion Diffusion: Bulk Single-Crystalline Metallic Silicon Clathrate.

Na-free Si clathrates consisting only of Si cages are an allotrope of diamond-structured Si. This material is promising for various device applications, such as next-generation photovoltaics. The probable technique for synthesizing Na-free Si clathrates is to extract Na+ from the Si cages of Na24 Si136 . Vacuum annealing is presently a well-known conventional and effective approach for extracting Na. However, this study demonstrates that Na+ cannot be extracted from the surface of a single-crystalline type-II metallic Si clathrate (Na24 Si136 ) in areas deeper than 150 µm. Therefore, a novel method is developed to control anisotropic ion diffusion: this is effective for various compounds with a large difference in the bonding strength between their constituent elements, such as Na24 Si136 composed of covalent Si cages and weakly trapped Na+ . By skillfully exploiting the difference in the chemical potentials as a driving force, Na+ is homogeneously extracted regardless of the size of the single crystal while maintaining high crystallinity. Additionally, the proposed point defect model is evaluated via density functional theory, and the migration of Na+ between the Si cages is explained. It is expected that the developed experimental and computational techniques would significantly advance material design for synthesizing thermodynamically metastable materials.

Robustness of Voltage-induced Magnetocapacitance.

One of the most important achievements in the field of spintronics is the development of magnetic tunnel junctions (MTJs). MTJs exhibit a large tunneling magnetoresistance (TMR). However, TMR is strongly dependent on biasing voltage, generally, decreasing with applying bias. The rapid decay of TMR was a major deficiency of MTJs. Here we report a new phenomenon at room temperature, in which the tunneling magnetocapacitance (TMC) increases with biasing voltage in an MTJ system based on Co40Fe40B20/MgO/Co40Fe40B20. We have observed a maximum TMC value of 102% under appropriate biasing, which is the largest voltage-induced TMC effect ever reported for MTJs. We have found excellent agreement between theory and experiment for the bipolar biasing regions using Debye-Fröhlich model combined with quartic barrier approximation and spin-dependent drift-diffusion model. Based on our calculation, we predict that the voltage-induced TMC ratio could reach 1100% in MTJs with a corresponding TMR value of 604%. Our work has provided a new understanding on the voltage-induced AC spin-dependent transport in MTJs. The results reported here may open a novel pathway for spintronics applications, e.g., non-volatile memories and spin logic circuits.

Experimental and Theoretical Evaluations of the Galvanomagnetic Effect in an Individual Bismuth Nanowire.

The galvanomagnetic effect is evaluated experimentally and theoretically in an individual bismuth nanowire encapsulated within a quartz template. A small section of the side surface of the encapsulated bismuth nanowire is exposed using focused ion beam processing, and a total of six carbon film electrodes are fabricated on the exposed nanowire surface by in situ deposition in order to be able to perform electrical measurements on the nanowire. The results show that the galvanomagnetic effect in the nanowire is affected by carrier collisions at the nanowire boundary; this is particularly the case at low temperatures. The Hall mobilities of electrons and holes are determined based on the measured Hall coefficient and magnetoresistivity values. It is found that the carrier mobility in the bismuth nanowire is lower than that in bulk bismuth and that it plateaus at low temperatures, as predicted by the calculation model used in the study, which takes into account the carrier mean free path limitation imposed by the small diameter of the nanowire.

Effect of a pinning field on the critical current density for current-induced domain wall motion in perpendicular magnetic anisotropy nanowires.

In this study, the effect of a pinning field on the critical current density for current-induced domain wall motion in nanowires with perpendicular magnetic anisotropy was investigated using micromagnetic simulations. In order to estimate the pinning field in notched nanowires, we conducted wall energy calculations for nanowires with various saturation magnetizations. The pinning field increased as the notch size increased. The pinning field decreased as the saturation magnetization decreased. As a result, the decreased in the pinning field causes the reduction of the critical current density. Therefore, a significant reduction of the critical current density can be obtained by decreasing the saturation magnetization, even if wall pinning occurs.

Preparation of bismuth nanowire encased in quartz template for Hall measurements using focused ion beam processing.

Forming electrodes on opposite sides of an individual bismuth nanowire was attempted to prepare for Hall measurements. Although a 1-mm-long bismuth nanowire which is completely covered with a quartz template has been successfully fabricated to prevent oxidation, it is very difficult to attach Hall electrodes on the opposite sides of the nanowire due to the quartz covering. One side of the cylindrical quartz template was removed by polishing without exposure of the nanowire to the atmosphere; the thickness between the polished template surface and the nanowire was estimated to be several micrometers. Focused ion beam processing was successfully employed to expose both surfaces of the nanowire under high vacuum by removing part of the quartz template. A carbon thin film was then deposited in situ on the wire surface to fabricate an electrical contact on the bismuth nanowire sample. Furthermore, the energy dispersive X-ray analysis was performed to the area processed by focused ion beam, and the bismuth component of the nanowire was successfully detected. It was confirmed that the focused ion beam processing was applicable to attach electrodes to bismuth nanowire for Hall measurement.

Reduction of temperature fluctuation within low temperature region using a cryocooler.

Modeling and experiments are performed to decrease temperature fluctuation generated by the periodic motion of the displacer in a Gifford-McMahon (GM) type cryocooler within the low-temperature region. The one-dimensional heat equation allows us to show that thermal diffusivity is an essential factor to achieve much smaller temperature fluctuation, and fiber-reinforced plastic (FRP) with low thermal diffusivity makes it possible to reduce the temperature fluctuation dramatically. Based on the model, experiments are performed to vary the thickness of two FRP dampers, on the cryohead of the cryocooler and on the sample stage. As a result, the FRP dampers enable us to achieve the temperature fluctuations of only 0.7 mK, corresponding to a standard deviation of 0.25 mK, when the sample stage is maintained at 4.2000 K, even if a GM cryocooler is utilized for cooling the temperature, which introduces an initial temperature fluctuation of 282 mK at the cryohead.

Novel dihydrothieno[2,3-e]indazole derivatives as IκB kinase inhibitors.

Synthesis, and structure-activity relationship (SAR) studies of the novel IKK-ß inhibitors 2 and 3 characterized by a dihydrothieno[2,3-e]indazole core are presented. Compound 2t was efficacious in a mouse model of LPS-stimulated TNF-α production.

High-precision temperature control and stabilization using a cryocooler.

We describe a method for precisely controlling temperature using a Gifford-McMahon (GM) cryocooler that involves inserting fiber-reinforced-plastic dampers into a conventional cryosystem. Temperature fluctuations in a GM cryocooler without a large heat bath or a stainless-steel damper at 4.2 K are typically of the order of 200 mK. It is particularly difficult to control the temperature of a GM cryocooler at low temperatures. The fiber-reinforced-plastic dampers enabled us to dramatically reduce temperature fluctuations at low temperatures. A standard deviation of the temperature fluctuations of 0.21 mK could be achieved when the temperature was controlled at 4.200 0 K using a feedback temperature control system with two heaters. Adding the dampers increased the minimum achievable temperature from 3.2 to 3.3 K. Precise temperature control between 4.200 0 and 300.000 K was attained using the GM cryocooler, and the standard deviation of the temperature fluctuations was less than 1.2 mK even at 300 K. This technique makes it possible to control and stabilize the temperature using a GM cryocooler.

Synthesis and structure-activity relationship studies of highly potent novel oxazolidinone antibacterials.

Novel antibacterial biaryl oxazolidinones bearing an aza-, an oxa-, or a thiabicyclo[3.1.0]hex-6-yl ring system were synthesized, and their in vitro antibacterial activity and structure-activity relationships (SAR) were evaluated. Most of the synthesized biaryl bicyclo[3.1.0]hex-6-yl oxazolidinones showed good antibacterial activity against the Gram-positive and -negative bacteria tested. Regarding SAR trends among the C-ring subtypes, the pyridyl ring was preferable to the phenyl ring. The results showed that the structural variety of the C-ring has a greater impact on antibacterial activity than that of the B-ring. A cyano group at the D-ring C-6 position plays an important role in the highly potent antibacterial activity.