OBJECTIVE Nicotinamide adenine dinucleotides (NAD⁺ and NADH) play a crucial role in cellular energy metabolism, and a dysregulated NAD⁺-to-NADH ratio is implicated in metabolic syndrome. However, it is still unknown whether a modulating intracellular NAD⁺-to-NADH ratio is beneficial in treating metabolic syndrome. We tried to determine whether pharmacological stimulation of NADH oxidation provides therapeutic effects in rodent models of metabolic syndrome. RESEARCH DESIGN AND METHODS We used β-lapachone (βL), a natural substrate of NADH:quinone oxidoreductase 1 (NQO1), to stimulate NADH oxidation. The βL-induced pharmacological effect on cellular energy metabolism was evaluated in cells derived from NQO1-deficient mice. In vivo therapeutic effects of βL on metabolic syndrome were examined in diet-induced obesity (DIO) and ob/ob mice. RESULTS NQO1-dependent NADH oxidation by βL strongly provoked mitochondrial fatty acid oxidation in vitro and in vivo. These effects were accompanied by activation of AMP-activated protein kinase and carnitine palmitoyltransferase and suppression of acetyl-coenzyme A (CoA) carboxylase activity. Consistently, systemic βL administration in rodent models of metabolic syndrome dramatically ameliorated their key symptoms such as increased adiposity, glucose intolerance, dyslipidemia, and fatty liver. The treated mice also showed higher expressions of the genes related to mitochondrial energy metabolism (PPARγ coactivator-1α, nuclear respiratory factor-1) and caloric restriction (Sirt1) consistent with the increased mitochondrial biogenesis and energy expenditure. CONCLUSIONS Pharmacological activation of NADH oxidation by NQO1 resolves obesity and related phenotypes in mice, opening the possibility that it may provide the basis for a new therapy for the treatment of metabolic syndrome.

A K-band CMOS voltage-controlled oscillator (VCO) is implemented with a 0.18- ¿m radio frequency CMOS process. For low supply voltage operation, a transformer-feedback topology using a transformer is proposed. The analysis of the transformer-feedback VCO is presented. This shows that the inductance ratio of the transformer must be optimized, and asymmetric-width transformers allow the easy optimization and the high Q-factor. Based on this analysis, the transformer design consideration of the transformer feedback VCO is presented. The VCO operates at 24.27 GHz with the phase noise of -100.33 dBc/Hz at 1-MHz offset, and it consumes 7.8 mW from a 0.65-V supply voltage.

The BRAF^V600E mutation leading to constitutive signaling of MEK-ERK pathways causes papillary thyroid cancer (PTC). Ras association domain family 1A (RASSF1A), which is an important regulator of MST1 tumor suppressor pathways, is inactivated by hypermethylation of its promoter region in 20 to 32% of PTC. However, in PTC without RASSF1A methylation, the regulatory mechanisms of RASSF1A-MST1 pathways remain to be elucidated, and the functional cooperation or cross regulation between BRAF^V600E and MST1,which activates Foxo3,has not been investigated. The negative regulators of the cell cycle, p21 and p27, are strongly induced by transcriptional activation of FoxO3 in BRAF^V600E positive thyroid cancer cells. The FoxO3 transactivation is augmented by RASSF1A and the MST1 signaling pathway. Interestingly, introduction of BRAF^V600Emarkedly abolished FoxO3 transactivation and resulted in the suppression of p21 and p27 expression. The suppression of FoxO3 transactivation by BRAF^V600Eis strongly increased by coexpression of MST1 but it is not observed in the cells in which MST1, but not MST2,is silenced. Mechanistically, BRAF^V600Ewas able to bind to the C-terminal region of MST1 and resulted in the suppression of MST1 kinase activities. The induction of the G1-checkpoint CDK inhibitors, p21 and p27,by the RASSF1A-MST1-FoxO3 pathway facilitates cellular apoptosis, whereasaddition of BRAF^V600E inhibits the apoptotic processes through the inactivation of MST1. Transgenic induction of BRAF^V600Ein the thyroid gland results in cancers resembling human papillary thyroid cancers. The development of BRAF^V600Etransgenic mice with the MST1 knockout background showed that these mice had abundant foci of poorly differentiated carcinomas and large areas without follicular architecture or colloid formation. The results of this study revealed that the oncogenic effect of BRAF^V600E is associated with the inhibition of MST1 tumor suppressor pathways, and that the activity of RASSF1A-MST1-FoxO3 pathways determines the phenotypes of BRAF^V600E tumors.

This letter proposes an effective output matching technique using drain shunt capacitors with tapered capacitance values for a GaN distributed power amplifier MMIC to simultaneously obtain optimum load impedance for maximum output power of each transistor and phase velocity balance between input and output artificial transmission lines as well as length reduction of the transmission lines. To support its plausibility, a 2-6 GHz 10 W distributed power amplifier MMIC is designed and fabricated using a 0.25 μm GaN HEMT process of WIN Semiconductors. Measurement of the S parameters and CW output power demonstrates successful operation of the proposed technique in the design frequency range.

This paper presents a general intermodulation read-out principle for passive wireless sensors. A sensor utilizes a mixing element, such as a varactor, and it can be equipped with a capacitive, inductive, or resistive sensor element. When the sensor is illuminated with signals with two frequencies, it replies the sensor data at an intermodulation frequency. An analytical expression for the intermodulation response of the sensor is derived and verified by simulations. The concept is demonstrated at 1.2 GHz.

An X-band monolithic microwave integrated circuit (MMIC) power amplifier for Synthetic Aperture Radar (SAR) systems has been implemented using a 0.25 μm AlGaN/GaN HEMT process on a SiC substrate. The MMIC power amplifier has an output power of 45 dBm (30 W) to 46 dBm (40 W) and a power-added efficiency of 38-44 % from 8.8 to 10.4 GHz with an associated power gain of 17 dB under the pulsed bias condition of a 10% duty cycle and 100 μs pulse width. The developed MMIC power amplifier will be applied to the solid-state power amplifier (sSPA) for future satellite SAR systems.