Oblongifolin C (OC) was identified as a potent apoptosis inducer from an herbal plant, Garcinia yunnanensis, during our previous bioassay-guided drug screening. In this study, we investigated the signaling pathways through which OC activated apoptosis in HeLa cells. We also compared the IC 50 values of OC with that of etoposide, paclitaxel and vinblastine in multiple cancer cell lines including HER2 and P-glycoprotein overexpressing cells. In addition, the in vivo antitumor effect of OC was studied in nude mice model. Our results showed that OC induced a caspase-dependent apoptosis by triggering a series of events in HeLa cells including Bax translocation, cytochrome c release, caspase-3 activation, chromosome fragmentation followed by caspase-8 activation, Bid cleavage and eventually cell death. Addition of a pan-caspase inhibitor or overexpression of an anti-apoptotic protein, Bcl-xL, prevented OC-induced cell death. Moreover, OC exhibited a wide anticancer spectrum in multiple cancer cell lines with comparable IC 50 values, regardless of the expression levels of HER2 and P-glycoprotein. In contrast, the IC 50 values of three clinical anticancer drugs, etoposide, paclitaxel and vinblastine were significantly elevated in HER2 and/or P-glycoprotein overexpressing cells. Furthermore, OC showed a similar antitumor effect but lower general toxicity than etoposide against xenografted human tumors in nude mice model. All these data suggested that OC is a promising apoptosis inducer with the potential to be developed into a clinical anticancer drug.

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We investigate the behavior of spiral waves in a quasi-two-dimensional spatial open reactor using Belousov-Zhabotinsky reaction. The goal of this study is to answer two questions raised recently: Can a system sustain a stable long-wavelength modulated spiral? What causes the transition from spiral to defect-mediated turbulence? Our experimental results show that in a certain range of control parameters, a sustained long-wavelength modulated spiral is stable. The amplitude and the wavelength of modulations increase with the control parameter. As the latter is increased to across a threshold, defects are generated far away from the spiral center as a result of the neighboring two wave fronts being too close.

During apoptosis, a key event is the release of Smac/DIABLO (an inhibitor of XIAP) and cytochrome c (Cyt-c, an activator of caspase-9) from mitochondria to cytosol. It was not clear, however, whether the releasing mechanisms of these two proteins are the same. Using a combination of single living-cell analysis and immunostaining techniques, we investigated the dynamic process of Smac and Cyt-c release during UV-induced apoptosis in HeLa cells. We found that YFP-labeled Smac and GFP-labeled Cyt-c were released from mitochondria in the same time window, which coincided with the mitochondrial membrane potential depolarization. Furthermore, using immunostaining, we found that the endogenous Smac and Cyt-c were always released together within an individual cell. Finally, when cells were pre-treated with caspase inhibitor (z-VAD-fmk) to block caspase activation, the process of Smac release, like that of Cyt-c, was not affected. This was true for both YFPlabeled Smac and endogenous Smac. These results suggest that in HeLa cells, both Smac and Cyt-c are released from mitochondria during UV-induced apoptosis through the same permeability transition mechanism, which we believe is triggered by the aggregation of Bax in the outer mitochondrial membrane to form lipid-protein complex.

Piezoelectric actuator (PEA) is an ideal microscale and nanoscale actuator because of its ultra-precision positioning resolution. However, the inherent hysteretic nonlinearity significantly degrades the PEA’s accuracy. The measured hysteresis of PEA exhibits strong rate-dependence and saturation phenomena, increasing the difficulty in the hysteresis modeling and identification. In this paper, a modified Prandtl-Ishlinskii (PI) hysteresis model is proposed. The weights of the backlash operators are updated according to the input rates so as to account for the rate-dependence property. Subsequently, the saturation property is realized by cascading a polynomial operator with only odd powers. In order to improve the efficiency of the parameter identification, a special control input consisting of a superimposition of multiple sinusoidal signals is utilized. Because the input rate of such a control input covers a wide range, all the parameters of the hysteresis model can be identified through only one set of experimental data, and no additional curve-fitting is required. The effectiveness of the hysteresis modeling and identification methodology is verified on a PEA-driven flexure mechanism. Experimental results show that the modeling accuracy is on the same order of the noise level of the overall system.

Using the ferroin-catalyzed Belosov-Zhabotinsky (BZ) reaction with the addition of an activating reactant in a reaction-diffusion system, we experimentally studied the competition between target waves and spiral waves when the system was in an oscillatory state. We found that when the period of background oscillation is smaller than that of spiral waves, target waves automatically appear in the reaction medium despite of the presence of spiral waves. The target waves compete with spiral waves and eventually win over the spirals, driving them out of the reaction medium. We also carried out numerical simulations using a modified Oregonator model. Our simulation results qualitatively agree with the experimental observations.

To tune the magnetic properties of hexagonal ferrites, a family of magnetoelectric multiferroic materials, by atomic-scale structural engineering, we studied the effect of structural distortion on the magnetic ordering temperature (TN). Using the symmetry analysis, we show that unlike most antiferromagnetic rareearth transition-metal perovskites, a larger structural distortion leads to a higher TN in hexagonal ferrites and manganites, because the K3 structural distortion induces the three-dimensional magnetic ordering, which is forbidden in the undistorted structure by symmetry. We also revealed a near-linear relation between TN and the tolerance factor and a power-law relation between TN and the K3 distortion amplitude. Following the analysis, a record-high TN (185 K) among hexagonal ferrites was predicted in hexagonal ScFeO3 and experimentally verified in epitaxially stabilized films. These results add to the paradigm of spin-lattice coupling in antiferromagnetic oxides and suggests further tunability of hexagonal ferrites if more lattice distortion can be achieved.

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