Background-Obesity is a major risk factor for the development of cardiovascular disease. Emerging evidence indicates that leptin, a protein encoded by the obesity gene, is linked with cardiac hypertrophy in obese humans and directly induces cardiomyocyte hypertrophy in vitro. However, the mechanisms by which leptin induces cardiomyocyte hypertrophy are poorly understood. Methods and Results-This study investigated how leptin contributes to cardiomyocyte hypertrophy. Cultured neonatal rat cardiomyocytes were used to evaluate the effects of leptin on hypertrophy. Both endothelin-1 (ET-1) and reactive oxygen species (ROS) levels were elevated in a concentration-dependent manner in cardiomyocytes treated with leptin for 4 hours compared with those cells without leptin treatment. ET-1 stimulated ROS production in a concentrationdependent manner in cardiomyocytes. The augmentation of ROS levels in cardiomyocytes treated with both leptin and ET-1 was reversed by a selective ET A receptor antagonist, ABT-627, and catalase, a hydrogen peroxide-decomposing enzyme. After treatment for 72 hours, leptin or ET-1 concentration-dependently increased total RNA levels, cell surface areas, and protein synthesis in cardiomyocytes, all of which were significantly inhibited by ABT-627 or catalase treatment. Conclusions-These findings indicate that leptin elevates ET-1 and ROS levels, resulting in hypertrophy of cultured neonatal rat cardiac myocytes. The ET-1-ET A -ROS pathway may be involved in cardiomyocyte hypertrophy induced by leptin. ET A receptor antagonists and antioxidant therapy may provide an effective means of ameliorating cardiac dysfunction in obese humans.

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Multilevel programing and charge transport characteristics of intrinsic SiOx-based resistive switching memory are investigated using TaN/SiOx/n++Si (MIS) and TiW/SiOx/TiW (MIM) device structures. Current transport characteristics of high- and low-resistance states (HRS and LRS) are studied in both device structures during multilevel operation. Analysis of device thermal response demonstrates that the effective electron energy barrier is strongly dependent on the resistance of the programed state, with estimates of 0.1 eV in the LRS and 0.6 eV in the HRS. Linear data fitting and conductance analyses indicate Poole-Frenkel emission or hopping conductance in the low-voltage region, whereas Fowler-Nordheim (F-N) or trap-assisted tunneling (TAT) is indicated at moderate voltage. Characterizations using hopping transport lead to hopping distance estimates of ∼1 nm in the LRS for both device structures. Relative permittivity values (εr) were extracted using the Poole-Frenkel formulism and estimates of local filament temperature, where εr values were ∼80 in the LRS and ∼4 in the HRS, suggesting a strongly polarized medium in the LRS. The onset of F-N tunneling or TAT corresponds to an observed “overshoot” in the I-V response with an estimated threshold of 1.6 ± 0.2 V, in good agreement with reported electro-luminescence results for LRS devices. Resistive switching is discussed in terms of electrochemical reactions between common SiO2 defects, and specific defect energy levels are assigned to the dominant transitions in the I-V response. The overshoot response in the LRS is consistent with TAT through either the Eγ' oxygen vacancy or the hydrogen bridge defect, both of which are reported to have an effective bandgap of 1.7 eV. The SET threshold at ∼2.5 V is modeled as hydrogen release from the (Si-H)2 defect to generate the hydrogen bridge, and the RESET transition is modeled as an electrochemical reaction that re-forms (SiH)2. The results provide further insights into charge transport and help identify potential switching mechanisms in SiOx-based unipolar resistive switching memory.

The physical mechanisms of unipolar resistive switching (RS) in SiOx-based resistive memory are investigated using TaN/SiOx/n++Si and TiW/SiOx/TiW device structures. RS is independent of SiOx thickness and device area, confirming that RS occurs in a localized region along a filamentary pathway. Results from experiments varying electrode type, series resistance, and the oxygen content of SiOxNy materials show the potential to optimize switching performance and control device programming window. Device materials with stoichiometry near that of SiO2 are found to have better operating stability as compared to extrinsic, N-doped SiOxNy materials. The results provide further insight into the physical mechanisms of unipolar operation and lead to a localized switching model based on electrochemical transitions involving common SiOx defects. High-temperature data retention measurements for over 104 s in high- and low-resistance states demonstrate the potential for use of intrinsic SiOx RS devices in future nonvolatile memory applications.

In the present study, we provide detailed insights into perillaldehyde (PAE)'s mechanisms of action on Aspergillus flavus and offer evidence in favor of the induction of an apoptosis-like phenotype. Specifically, PAE's antifungal mode of action was investigated through the detection of mitochondrial membrane potential (MtΔψ) and phosphatidylserine (PS) exposure, as well as intracellular Ca level, reactive oxygen species accumulation, and metacaspase activation. This was done by way of fluorometry, measuring DNA fragmentation, and condensation by fluorescent microscopy. Furthermore, we searched for phenotypic changes characteristic of apoptosis by transmission electron microscopy and flow cytometry, determining the amount of cytochrome c released using Western blotting. Results indicated that cultivation of A. flavus in the presence of PAE caused depolarization of MtΔψ, rapid DNA condensation, large-scale DNA fragmentation, and an elevation of intracellular Ca level. The percentage of early apoptotic cells with exposure of PS were 27.4% and 48.7%, respectively, after 9 h incubations with 0.25 and 0.5 μL/mL of PAE. The percentage of stained cells with activated intracellular metacaspases exposed to PAE at concentrations of 0.25 and 0.5 μL/mL compared with control subjects were increased by 28.4 ± 3.25% and 37.9 ± 4.24%, respectively. The above results has revealed that PAE induces fungal apoptosis through a caspase-dependent mitochondrial pathway. In all, our findings provide a novel mechanism for exploring a possible antifungal agent used in food preservation.

Articles you may be interested inIntrinsic SiOx-based unipolar resistive switching memory. II. Thermal effects on charge transport and characterization of multilevel programing Intrinsic SiOx-based unipolar resistive switching memory. I. Oxide stoichiometry effects on reversible switching and program window optimizationThe resistive switching characteristics and mechanism in active SiO x -based resistive switching memory have been investigated by using a simple TaN/SiO 2 /n þþ Si-substrate test structure. Controlling the oxygen content in SiO x layer not only improved device yield but also stabilized electrical switching characteristics. The current transport behavior in high-and low-resistance states, thickness effect in SiO x layer, device area effect, and multilevel effect by controlling compliance current limitation and stopped voltage values have been studied. The results indicate that resistive switching occurs in a localized region along a filament, rather than uniformly throughout the bulk. A general current flow model for nonpolar SiO x -based resistive switching memory has been proposed, which provides a simple physical concept to describe the resistive switching behavior and provides additional insights into optimization of resistive switching memory devices. V C 2012 American Institute of Physics. [http://dx.

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Figure 1: Structural co-hierarchical analysis of a set of velocipedes (bicycles, tricycles and four-cycles). The resulting co-hierarchy (center) is illustrated by a single sample shape from the set, where each node represents a part assembly. Two of the nodes (highlighted in blue and green) are expanded to show the insight gained by the analysis which relates parts with rather different geometries but similar functions. AbstractWe introduce an unsupervised co-hierarchical analysis of a set of shapes, aimed at discovering their hierarchical part structures and revealing relations between geometrically dissimilar yet functionally equivalent shape parts across the set. The core problem is that of representative co-selection. For each shape in the set, one representative hierarchy (tree) is selected from among many possible interpretations of the hierarchical structure of the shape. Collectively, the selected tree representatives maximize the within-cluster structural similarity among them. We develop an iterative algorithm for representative co-selection. At each step, a novel cluster-and-select scheme is applied to a set of candidate trees for all the shapes. The tree-to-tree distance for clustering caters to structural shape analysis by focusing on spatial arrangement of shape parts, rather than their geometric details. The final set of representative trees are unified to form a structural co-hierarchy. We demonstrate co-hierarchical analysis on families of man-made shapes exhibiting high degrees of geometric and finer-scale structural variabilities.