Search

An alternate application of MgO film for the improvement of discharge characteristics and lifetime in an ac plasma display panel (PDP) is suggested. In the normal ramp reset, the accumulated wall charges on the phosphor surface just after the reset period are different as to their color (red, green, blue) of each phosphor, which reduces the common voltage margin of ac PDP. In general, MgO is used for the protective layer of dielectrics from ion sputtering and the improvement of secondary electron emission which affects the driving voltage in an ac PDP. In this research, we deposited MgO on the phosphor to get the same addressing characteristics irrespective to the color of each phosphor, high speed addressing, and prolonged lifetime of phosphor despite the vacuum ultraviolet irradiation and ion bombardment. An optimized MgO thickness was used to avoid the excessive luminance and luminous efficacy degradation by the MgO deposition on the phosphor. Results showed that PDP with MgO coated phosphor has more uniform formative delays in address discharges and improved degradation characteristics. [ABSTRACT FROM AUTHOR]

Dynamic nucleocytoplasmic shuttling of class IIa histone deacetylases (HDACs) is a fundamental mechanism regulating gene transcription. Recent studies have identified several protein kinases that phosphorylate HDAC5, leading to its exportation from the nucleus. However, the negative regulatory mechanisms for HDAC5 nuclear exclusion remain largely unknown. Here we show that cAMP-activated protein kinase A (PKA) specifically phosphorylates HDAC5 and prevents its export from the nucleus, leading to suppression of gene transcription. PKA interacts directly with HDAC5 and phosphorylates HDAC5 at serine 280, an evolutionarily conserved site. Phosphorylation of HDAC5 by PKA interrupts the association of HDAC5 with protein chaperone 14-3-3 and hence inhibits stress signal-induced nuclear export of HDAC5. An HDAC5 mutant that mimics PKA-dependent phosphorylation localizes in the nucleus and acts as a dominant inhibitor for myocyte enhancer factor 2 transcriptional activity. Molecular manipulations of HDAC5 show that PKA-phosphorylated HDAC5 inhibits cardiac fetal gene expression and cardiomyocyte hypertrophy. Our findings identify HDAC5 as a substrate of PKA and reveal a cAMP/PKA-dependent pathway that controls HDAC5 nucleocytoplasmic shuttling and represses gene transcription. This pathway may represent a mechanism by which cAMP/PKA signaling modulates a wide range of biological functions and human diseases such as cardiomyopathy. [ABSTRACT FROM AUTHOR]

Vascular endothelial growth factor (VEGF) is essential for normal and pathological angiogenesis. However, the signaling pathways linked to gene regulation in VEG F-induced angiogenesis are not fully understood. Here we demonstrate a critical role of protein kinase D (PKD) and histone deacetylase 5 (HDAC5) in VEGF-induced gene expression and angiogenesis. We found that VEGF stimulated HDAC5 phosphorylation and nuclear export in endothelial cells through a VEGF receptor 2-phospholipase Cγ-protein kinase C-PKD-dependent pathway. We further showed that the PKD-HDAC5 pathway mediated myocyte enhancer factor-2 transcriptional activation and a specific subset of gene expression in response to VEGF, including NR4A1, an orphan nuclear receptor involved in angiogenesis. Specifically, inhibition of PKD by overexpression of the PKD kinase-negative mutant prevents VEGF-induced HDAC5 phosphorylation and nuclear export as well as NR4A1 induction. Moreover, a mutant of HDAC5 specifically deficient in PKD-dependent phosphorylation inhibited VEGF-mediated NR4A1 expression, endothelial cell migration, and in vitro angiogenesis. These findings suggest that the PKD-HDAC5 pathway plays an important role in VEGF regulation of gene transcription and angiogenesis. [ABSTRACT FROM AUTHOR]

In this paper, the operation characteristics of an ac plasma display panel (PDP) with Si-doped MgO protecting layer are investigated. The test panels are fabricated with the protecting layers of conventional MgO and Si-doped MgO, and the operation voltage margin, luminous efficacy, and address discharge time lag are observed. Even though the test panel with Si-doped MgO protecting layer showed lower operation voltages, higher luminous efficacy, and shorter statistical discharge time lag, its addressing discharge characteristics become deteriorated as the scanning time is increased from the end time of the reset period. The photon-induced surface conductivity increased by Si doping into MgO, and surface charges on the Si-doped MgO protecting layer showed faster decay characteristics compared to those on the conventional one. It is believed that the impurity doping into the protecting layer can improve the short-period characteristics of an ac PDP, but the long-term stability of surface charge retention is deteriorated. [ABSTRACT FROM AUTHOR]

Vascular endothelial growth factor (VEGF) is a potent mediator of angiogenesis and vascular permeability, in which c-Src tyrosine kinase plays an essential role. However, the mechanisms by which VEGF stimulates c-Src activation have remained unclear. Here, we demonstrate that vascular endothelial cadherin (VE-cadherin) plays a critical role in regulating c-Src activation in response to VEGF. In vascular endothelial cells, VE-cadherin was basally associated with c-Src and Csk (C-terminal Src kinase), a negative regulator of Src activation. VEGF stimulated Csk release from VE-cadherin by recruiting the protein tyrosine phosphatase SHP2 to VE-cadherin signaling complex, leading to an increase in c-Src activation. Silencing VE-cadherin with small interference RNA significantly reduced VEGF-stimulated c-Src activation. Disrupting the association of VE-cadherin and Csk through the reconstitution of Csk binding-defective mutant of VE-cadherin also diminished Src activation. Moreover, inhibiting SHP2 by small interference RNA and adenovirus-mediated expression of a catalytically inactive mutant of SHP2 attenuated c-Src activation by blocking the disassociation of Csk from VE-cadherin. Furthermore, VE-cadherin and SHP2 differentially regulates VEGF downstream signaling. The inhibition of c-Src, VE-cadherin, and SHP2 diminished VEGF-mediated activation of Akt and endothelial nitric-oxide synthase. In contrast, inhibiting VE-cadherin and SHP2 enhanced ERK1/2 activation in response to VEGF. These findings reveal a novel role for VE-cadherin in modulating c-Src activation in VEGF signaling, thus providing new insights into the importance of VE-cadherin in VEGF signaling and vascular function. [ABSTRACT FROM AUTHOR]

The objective of this study is to investigate experimentally the relationship between an operator's mental workload and the information flow rate of accident diagnosis tasks and further to propose the information flow rate as an analytic method for measuring the mental workload. There are two types of mental workload in the advanced main control room of nuclear power plants: the information processing workload, which is the processing that the human operator must actually perform in order to complete the diagnosis task, and emotional stress workload experienced by the operator. In this study, the focus is on the former. Three kinds of methods are compared to measure the operator's workload: information flow rate, subjective methods, and physiological measures. Information flows for eight accident diagnosis tasks are modeled qualitatively using a stage model and are quantified using Conant's model. The information flow rate is obtained by imposing time limit restrictions for the tasks. National Aeronautics and Space Administration-Task Load Index (NASA-TLX) and Modified Cooper-Harper (MCH) scale are selected as subjective methods. For the physiological measurements, an eye tracking system analyzes eye movements related to the operator's blinking and fixation on regions of interests. Through the experiments, the relationship between the information flow rate of accident diagnosis tasks and the selected measures is investigated. Results indicate that the information flow rate of diagnosis tasks is in high agreement with both subjective rating scores and eye movement parameters related to blinking and fixation on the regions of interest. It appears, then, that information flow rate can be an alternative as an analytic approach for measuring mental workload. By using data on the information flow rate, we can predict the mental workload required for a task without performing experiments in advance. [ABSTRACT FROM AUTHOR]

Angiotensin II (Ang II) induces the phenotypic modulation and hypertrophy of vascular smooth muscle cells (VSMCs), which is implicated in the pathogenesis of hypertension and atherosclerosis. Here we established a novel role of histone deacetylases 5 (HDAC5) in Ang II-induced VSMC hypertrophy. We showed that Ang II rapidly stimulated phosphorylation of HDAC5 (p-HDAC5) on Ser259/498 sites in a time- and dose- dependent manner in rat aortic VSMCs. Ang II receptor 1 mediated p-HDAC5. Protein kinase C (PKC) inhibitors, GF109203X and Gö6983, inhibited p-HDAC5. Using pharmacological inhibitor, siRNA and adenovirus encoding kinase-negative mutant of protein kinase D (PKD) demonstrated that PKD was essential for p-HDAC5 by Ang II. Moreover, we showed that Ang II stimulated HDAC5 nuclear export, which was dependent on its phosphorylation via PKC/PKD pathway, because HDAC5 nuclear export was abolished by inhibiting PKC and PKD and by infection of adenovirus encoding HDAC5 S259/498A mutant. Furthermore, both PKD inhibition and HDAC5 S259/498A mutant blocked Ang II-induced myocyte enhancer factor 2 (MEF2) transcriptional activation. Importantly, Ang II promoted VSMC protein synthesis in PKD and HDAC5-dependent manner. Our findings reveal for the first time that PKD and HDAC5 play a key role in Ang II-induced VSMC hypertrophy, and suggest that PKD and HDAC5 may emerge as potential targets for cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Programmed cell death 5 (PDCD5) has been associated with human cancers as a regulator of cell death; however, the role of PDCD5 in the endothelium has not been revealed. Thus, we investigated whether PDCD5 regulates protein kinase B (PKB/AKT)-endothelial nitric oxide synthase (eNOS)-dependent signal transduction in the endothelium and affects atherosclerosis. Endothelial-specific PDCD5 knockout mice showed significantly reduced vascular remodeling compared with wild-type (WT) mice after partial carotid ligation. WT PDCD5 competitively inhibited interaction between histone deacetylase 3 (HDAC3) and AKT, but PDCD5L6R, an HDAC3-binding-deficient mutant, did not. Knockdown of PDCD5 accelerated HDAC3-AKT interaction, AKT and eNOS phosphorylation, and nitric oxide (NO) production in human umbilical vein endothelial cells. Moreover, we found that serum PDCD5 levels reflect endothelial NO production and are correlated with diabetes mellitus, high-density lipoprotein cholesterol, and coronary calcium in human samples obtained from the cardiovascular high-risk cohort. Therefore, we conclude that PDCD5 is associated with endothelial dysfunction and may be a novel therapeutic target in atherosclerosis. [ABSTRACT FROM AUTHOR]