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Am J Physiol Heart Circ Physiol 298: H33-H44, 2010. First published October 23, 2009; doi: 10.1152/ajpheart.00232.2009.--Timothy syndrome (TS) is a malignant form of congenital long QT syndrome with a mode of arrhythmia onset often triggered by enhanced sympathetic tone. We sought to explore mechanisms by which [beta]-adrenergic stimulation (BAS) modulates arrhythmogenesis and to identify potential targeted sites of antiarrhythmic therapy in TS. Using a dynamic Luo-Rudy ventricular myocyte model incorporated with detailed intracellular [Ca.sup.2+] cycling, along with its one-dimensional multicellular strand, we simulated various clinical scenarios of TS, with stepwise increase in the percentage of G406R [Ca.sub.v]l.2 channels from 0 to 11.5 and 23%, and to 38.5 and 77%, respectively, for heterozygous and homozygous states of TS1 and TS2. Progressive prolongation of action potential duration (APD) and QT interval, accompanied by amplification of transmural dispersion of repolarization, steepening of APD restitution, induction of delayed afterdepolariztions (DADs), and both DAD and phase 3 early afterdepolariztion-mediated triggered activities, correlated well with the extent of G406R [Ca.sub.v]l.2 channel mutation. BAS amplified transmural dispersion of repolarization, steepened APD restitution, and facilitated inducibility of DAD-mediated triggered activity. Systematic analysis of intracellular [Ca.sup.2+] cycling revealed that sarcoplasmic reticulum [Ca.sup.2+] ATPase (uptake current) played an essential role in BAS-induced facilitation of DAD-mediated triggered activity and, in addition to L-type calcium current, it could be an effective site of antiarrhythmic therapy under the influence of BAS. Thus G406R [Ca.sub.v]1.2 channel mutation confers not only a trigger, but also a substrate for lethal ventricular arrhythmias, which can be exaggerated by BAS. It is suggested that, besides [beta]-adrenergic blockers and L-type calcium current channel blockers, an agent aimed at reduction of sarcoplasmic reticulum [Ca.sup.2+] ATPase uptake current may provide additional antiarrhythmic effect in patients with TS. congenital long QT syndrome; computational biology; sudden cardiac death; ventricular arrhythmias

A novel rectifying antenna (rectenna) using a compact circularly polarized (CP) patch antenna with RF-to-DC power conversion part at 2.45 GHz is introduced, in which the unbalanced slots structure is adopted for size reduction and 2nd harmonic rejection. To contribute a rectenna for RF power conversion, the back side of the CP antenna is the doubler rectifier circuit with 3rd order harmonic rejection radial stub for efficiency optimization and harmonic power re-radiation elimination. The adopted CP antenna built on low cost FR-4 substrate has measured bandwidth of 137 MHz (10 dB return loss) as well as 30 MHz CP bandwidth (3 dB axial ratio). By up to 3rd order harmonic rejection, the RF-to-DC conversion efficiency would reach 53% and 75% with 1 K [omega] resistor load under ANSI/IEEE uncontrolled and controlled RF human exposure limit respectively. Index Terms--Circular polarization, patch antenna, rectifiers, rectifying antenna (rectenna), wireless power transmission (WPT).

Patients with Andersen-Tawil syndrome (ATS) mostly have mutations on the KCNJ2 gene, producing loss of function or dominant-negative suppression of the inward rectifier [K.sup.+] channel Kir2.1. However, clinical manifestations of ATS including dysmorphic features, periodic paralysis (hypo-, hyper-, or normokalemic), long QT, and ventricular arrhythmias (VAs) are considerably variable. Using a modified dynamic Luo-Rudy simulation model of cardiac ventricular myocytes, we attempted to elucidate mechanisms of VA in ATS by analyzing effects of the inward rectifier [K.sup.+] channel current ([I.sub.K1]) on the action potential (AP). During pacing at 1.0 Hz with extracellular [K.sup.+] concentration ([[[K.sup.+]].sub.o]) at 4.5 mM, a stepwise 10% reduction of Kit2.1 channel conductance progressively prolonged the terminal repolarization phase of the AP along with gradual depolarization of the resting membrane potential (RMP). At 90% reduction, early afterdepolarizations (EADs) became inducible and RMP was depolarized to -52.0 mV (control: -89.8 mV), followed by emergence of spontaneous APs. Both EADs and spontaneous APs were facilitated by a decrease in [[[K.sup.+]].sub.o] and suppressed by an increase in [[[K.sup.+]].sub.o]. Simulated [beta]-adrenergic stimulation enhanced delayed afterdepolarizations (DADs) and could also facilitate EADs as well as spontaneous APs in the setting of low [[[K.sup.+]].sub.o] and reduced Kir2.1 channel conductance. In conclusion, the spectrum of VAs in ATS may include 1) triggered activity mediated by EADs and/or DADs and 2) abnormal automaticity manifested as spontaneous APs. These VAs can be aggravated by a decrease in [[[K.sup.+]].sub.o] and [beta]-adrenergic stimulation and may potentially induce torsade de pointes and cause sudden death. In patients with ATS, the hypokalemic form of periodic paralysis should have the highest propensity to VAs, especially during physical activity. Andersen syndrome; long QT