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Aims Erythropoietin ( EPO), the key hormone involved in erythropoiesis, beneficially affects endothelial cells ( ECs), but the detailed mechanisms are yet to be completely understood. In this study, we investigated the role of transient receptor potential vanilloid type 1 ( TRPV1), a ligand-gated non-selective calcium (Ca2+) channel, in EPO-mediated endothelial nitric oxide synthase ( eNOS) activation and angiogenesis. Methods and results In ECs, EPO time dependently increased intracellular levels of calcium; this increase was abrogated by the Ca2+ chelators and pharmacological inhibitors of TRPV1 in bovine aortic ECs (BAECs) and TRPV1-transfected HEK293 cells. In addition, EPO-induced nitrite oxide ( NO) production, phosphorylation of eNOS, Akt and AMP-activated protein kinase ( AMPK) and the formation of TRPV1-Akt- AMPK- eNOS complex as well as tube formation were diminished by the pharmacological inhibition of TRPV1 in BAECs. Moreover, EPO time dependently induced the phosphorylation of phospholipase C- γ1 ( PLC- γ1). Inhibition of PLC- γ1 activity blunted the EPO-induced Ca2+ influx, eNOS phosphorylation, TRPV1- eNOS complex formation and NO production. The phosphorylated level of eNOS increased in the aortas of EPO-treated wild-type ( WT) mice or EPO-transgenic (Tg) mice but not in those of EPO-treated TRPV1-deficient ( TRPV1−/−) mice or EPO-Tg/ TRPV1−/− mice. Matrigel plug assay showed that EPO-induced angiogenesis was abrogated in TRPV1 antagonist capsazepine-treated WT mice and TRPV1−/− mice. Conclusion These findings indicate the EPO-induced Ca2+ influx via the activation of the PLC- γ1 signalling pathway, which leads to TRPV1 activation and consequently increases the association of the TRPV1-Akt- AMPK- eNOS complex, eNOS activation, NO production and angiogenesis. [ABSTRACT FROM AUTHOR]

Aims We investigated the role of transient receptor potential vanilloid receptor type 1 (TRPV1) in simvastatin-mediated activation of endothelial nitric oxide synthase ( eNOS) and angiogenesis. Methods Fluo-8 NW assay was for Ca2+ detection; Griess's assay was for NO bioavailability; Western blotting and immunoprecipitation were for protein phosphorylation and interaction; tube formation and Matrigel plug assay were for angiogenesis. Results In endothelial cells (ECs), treatment with simvastatin time-dependently increased intracellular level of Ca2+. Pharmacological inhibition or genetic disruption of TRPV1 abrogated simvastatin-mediated elevation of intracellular Ca2+ in ECs or TRPV1-transfected HEK293 cells. Loss of TRPV1 function abolished simvastatin-induced NO production and phosphorylation of eNOS and calmodulin protein kinase II (CaMKII) in ECs and in aortas of mice. Inhibition of TRPV1 activation prevented the simvastatin-elicited increase in the formation of TRPV1-Akt-CaMKII-AMPK- eNOS complex. In mice, Matrigel plug assay showed that simvastatin-evoked angiogenesis was abolished by TRPV1 antagonist and genetic ablation of TRPV1. Additionally, our results demonstrated that TRP ankyrin 1 (TRPA1) is the downstream effector in the simvastatin-activated TRPV1-Ca2+ signalling and in the consequent NO production and angiogenesis as evidence by that re-expression of TRPA1 further augmented simvastatin-elicited Ca2+ influx in TRPV1-expressed HEK293 cells and ablation of TRPA1 function profoundly inhibited the simvastatin-induced increase in the phosphorylation of eNOS and CaMKII, formation of TRPV1-Akt-CaMKII-AMPK- eNOS complex, NO bioavailability, tube formation and angiogenesis in ECs or mice. Conclusion Simvastatin-induced Ca2+ influx may through the activation of TRPV1-TRPA1 signalling, which leads to phosphorylation of CaMKII, increases in the formation of TRPV1-CaMKII-AMPK- eNOS complex, eNOS activation, NO production and, ultimately, angiogenesis in ECs. [ABSTRACT FROM AUTHOR]

Aims Soluble guanylyl cyclase (s GC) is a key modulator in the regulation of vascular tone. However, its role and involving mechanism in cholesterol metabolism of macrophages and atherosclerosis remain unclear. Methods Oil red O staining, Dil-oxidized low-density lipoprotein (ox LDL)-binding assay and cholesterol efflux assay were performed in biology of foam cells. Levels of cytokines or intracellular lipid were evaluated by ELISA or colorimetric kits. Expression of gene or protein was determined by quantitative real-time PCR or Western blotting. Histopathology was examined by haematoxylin and eosin staining. Results Soluble guanylyl cyclase was expressed in macrophages of mouse atherosclerotic lesions. Treatment with 1 H-[1, 2, 4]oxadiazolo[4,3-a]quinoxalin-1-one ( ODQ, s GC inhibitor) exacerbated ox LDL-induced cholesterol accumulation in macrophages. In contrast, 3-(5′-hydroxymethyl-2′furyl)-1-benzyl indazole ( YC-1, s GC activator) attenuated the ox LDL-induced cholesterol accumulation because of increased cholesterol efflux. Additionally, YC-1 dose dependently increased the protein expression of ATP-binding cassette transporter A1 ( ABCA1) but did not alter that of scavenger receptor class A ( SR- A), CD36, SR- BI or ABCG1. Moreover, YC-1-upregulated ABCA1 level depended on liver X receptor α ( LXR α). Inhibition of the LXR α- ABCA1 pathway by LXR α small interfering RNA (si RNA), ABCA1 neutralizing antibody or ABCA1 si RNA abolished the effect of YC-1 on cholesterol accumulation and cholesterol efflux. In vivo, YC-1 retarded the development of atherosclerosis, accompanied by reduced serum levels of cholesterol and pro-inflammatory cytokines, in apolipoprotein E-deficient mice. Conclusion Activation of s GC by YC-1 leads to LXR α-dependent upregulation of ABCA1 in macrophages and may confer protection against atherosclerosis. [ABSTRACT FROM AUTHOR]

Aims We investigated the effects and underlying molecular mechanism of transient receptor potential vanilloid 1 ( TRPV1), a calcium (Ca2+)-permeable non-selective cation channel, on phosphorylation of endothelial nitric oxide synthase (e NOS) at threonine 497 (Thr497) in bovine aortic endothelial cells ( BAECs) and in mice. Methods Western blotting and immunoprecipitation were used for the evaluation of protein phosphorylation; protein phosphatase 2 B ( PP2B) activity was assessed by convention kit; Griess assay was for NO production; tube formation and Matrigel plug assay were used for angiogenesis. Results In BAECs, treatment with the TRPV1 ligand evodiamine decreased the phosphorylation of e NOS at Thr497, protein kinase Cα ( PKCα) at Serine 657 (Ser657) and PKCβ2 at Ser660. Evodiamine increased protein phosphatase 2B (PP2B) activity and promoted the formation of a PP2B- PKC complex. Inhibition of TRPV1 activation by the pharmacological antagonists, removal of extracellular Ca2+ or pharmacological inhibition of PI3K/Akt/calmodulin-dependent protein kinase II/ AMP-activated protein kinase signalling pathway abolished the evodiamine-induced alterations in phosphorylation of e NOS at Thr497, PKCα at Ser657, PKCβ2 at Ser660 and PP2B activity, as well as the formation of a PP2B- PKC complex. Inhibition of PP2B activation partially reduced the evodiamine-induced NO bioavailability and tube formation in endothelial cells ( ECs) and angiogenesis in mice. Moreover, evodiamine decreased the phosphorylation of e NOS at Thr497, PKCα at Ser657 and PKCβ2 at Ser660 in apolipoprotein E (ApoE)-deficient mouse aortas but not TRPV1-deficient or ApoE/ TRPV1 double-knockout mice. Conclusion TRPV1 activation in ECs may elicit a Ca2+-dependent effect on PP2B- PKC signalling, which leads to dephosphorylation of e NOS at Thr497 in ECs and in mice. [ABSTRACT FROM AUTHOR]

Aim Environmental cigarette smoke ( CS) contains many compounds that are harmful to the respiratory system and lead to chronic lung inflammation and other lung diseases. Exercise training is known to confer protection against diseases with chronic inflammation by reducing inflammatory response in human or experimental animals. In this study, we investigated the preventive effect of exercise training against lung inflammation induced by environmental CS. Methods and results In this study, two groups of mice received air exposure with (the exercise group) or without (the control group) exercise training for 8 weeks and another two groups received air exposure for the first 4 weeks and CS exposure for the following 4 weeks with (the exercise+ CS group) or without (the CS group) exercise training for 8 weeks. As compared with lung tissues of control and exercise groups, those of the CS group showed significantly increased bronchoalveolar-capillary permeability, inflammatory cell infiltration, epithelial thickening, expression of proliferating cell nuclear antigen, mucin 2, cytokines, chemokines, adhesion molecules and activation of NF-κ B. These CS-induced pathophysiologic consequences were largely prevented in the exercise + CS group. Conclusion Collectively, prior exercise training may protect against lung inflammation induced by environmental CS in mice by attenuating the activation of NF-κ B and the production of inflammatory mediators. [ABSTRACT FROM AUTHOR]

The most stable structures of gaseous Si m C n (3 ⩽ n+ m ⩽ 6) clusters in their ground electronic states are determined with the high level electronic correlation method QCISD(T)/g3large. Thermodynamic properties on heat capacity ( C ), entropy ( S ), Gibbs energy function (−[ G Θ − H Θ( T r )]/ T) and enthalpy function ( H Θ− H Θ( T r )) are predicted with standard statistical thermodynamics using the structure parameters and vibrational frequencies obtained with B3PW91/6-31G( d) method combined with the electronic excitation energies determined with time dependent density functional (TD DFT) method at B3PW91/6-31G( d) level. The electronic energies are calculated with the accurate model chemistry method at G3(QCI) level of theory and the Δ f H (0 K), Δ f H (298.15 K) and Δ f G (298.15 K) values are predicted. The heat capacities C ( T) as a function of temperature within 298.15-2000 K are fitted into analytical equations. The thermodynamic functions at higher temperatures are determined classically by using these equations. Most of the results obtained in this work are consistent with the available experiments. [ABSTRACT FROM AUTHOR]

Elastic, strength, electronic properties and vibrational spectra of Ne@C60 (Ih) in its ground electronic state (X 1Ag) were investigated with density functional theory at B3PW91/6-31G level via structure distortions. The elastic properties were obtained from the potential energy curves (PECs) in all of the five independent distortional directions of the molecule with symmetries of 1. D5d, 2. D3d, 3. D2h, 4. C2h(1) and 5. C2h(2). PECs were examined where the structure of Ne@C60 was destroyed. The necessary energies to destroy the structure were thus obtained, which illuminated the stability of Ne@C60. PECs were found to be anisotropic and were accurately fitted to polynomials. Elongations in the direction of D5d and compression in D2h encountered potential energy surface cross-linkages, which might be considered as a single electron pump for further application in the design of single electron devices. Time-dependent B3PW91/6-31G analysis predicted significant electronic spectra changes associated with structure distortions. Similarities and differences of the properties were compared with those in C60 and He@C60. [ABSTRACT FROM AUTHOR]

An adaptive fuzzy total-sliding-mode controller (AFTSMC) with a total switching surface is proposed to control the position of an electrical servodrive. The proposed controller comprises a special fuzzy total-sliding-mode controller (FTSMC) and an adaptive tuner. The FTSMC acts as the main tracking controller, which is designed via a fuzzy system to mimic the merits of a total-sliding-mode controller (TSMC). In addition, a translation width is embedded into fuzzy rules to reduce the chattering phenomena. The adaptive tuner, which is derived in the sense of Lyapunov stability theorem, is utilised to adjust the translation width on-line for further assuring robust and optimal performance. In the AFTSMC, the fuzzy-control-rules base is compact and only one parameter needs to be adjusted. An electrical servodrive with the proposed position-control system possesses the advantages of a simple control framework, reduced chattering, stable performance and robustness to uncertainties. The effectiveness is demonstrated by simulated and experimental results, and its advantages are indicated in comparison with conventional TSMC and adaptive TSMC for a field-oriented control induction-motor (IM) drive. [ABSTRACT FROM AUTHOR]

An alternative control scheme including an enhanced genetic algorithm controller (EGAC) and a supervisory controller is developed for nonlinear dynamical systems in this study. In the EGAC design, the spirit of gradient descent training is embedded in genetic algorithm (GA) to construct a main controller to search the optimum control effort under the possible occurrence of uncertainties. To ensure the system states around a defined bound region, a supervisory controller, which is derived in the sense of Lyapunov stability theorem, is added to adjust the control effort. Compared with enunciated GA control methods, the proposed control scheme possesses some salient advantages of simple framework, less executing time and good self-organising properties even for the time-varying system because the simple solution representation and the error backpropagation genetic operation are utilised in the GA process. In addition, the proposed scheme is applied to the position control of a decoupling induction motor (IM) drive, whose effectiveness is verified by the numerical simulation and experimental results and whose advantages are presented in comparison with existing position control schemes. [ABSTRACT FROM AUTHOR]

OBJECTIVE:: To investigate whether vitamin B6 supplementation had a beneficial effect on lowering fasting plasma homocysteine concentrations in coronary artery disease (CAD) patients. DESIGN:: A single-blind intervention study. SETTING:: The study was performed at the Taichung Veterans General Hospital, the central part of Taiwan. SUBJECTS:: A total of 50 subjects were identified by cardiac catheterization to have at least 70% stenosis of one major coronary artery. In all, 42 patients successfully completed this study. INTERVENTIONS:: Patients were randomly assigned to one of five groups and treated with a daily dose of placebo (n=8), 5?mg vitamin B6 (n=8), 10?mg vitamin B6 (n=8), 50?mg vitamin B6 (n=9), or 5?mg folic acid combined with 0.25?mg vitamin B12 (n=9) for 12 weeks. MAIN OUTCOME MEASURES:: Nutrient intakes were recorded by using 24-h diet recalls when patients returned to the cardiology clinic before the intervention (week 0) and at week 12. Vitamin B6 status was assessed by direct measures (plasma pyridoxal 5'-phosphate) and indirect measures (erythrocyte alanine and aspartate aminotransaminase activity coefficient). Fasting plasma homocysteine, serum folic acid, and vitamin B12 were measured. RESULTS:: Fasting plasma homocysteine concentration did not respond to high or low doses of vitamin B6 when compared with a placebo treatment after 12 weeks of supplementation. The mean fasting plasma homocysteine concentration, however, decreased significantly after 12 weeks of folic acid combined with vitamin B12 supplementation (P=0.047). Further, within group, mean fasting plasma homocysteine concentration was nonsignificantly increased by 25.5, 16.2, and 18.3% in placebo, 10?mg/day and 50?mg/day vitamin B6 supplemented groups, respectively; whereas folic acid combined with vitamin B12 supplementation significantly reduced fasting plasma homocysteine concentration by 32% (P<0.001). CONCLUSIONS:: Our results indicate that vitamin B6 supplementation alone is less effective than folic acid combined with vitamin B12 in lowering plasma homocysteine concentrations in CAD patients. SPONSORSHIP:: This study was supported by the National Science Council, Taiwan, Republic of China (NSC-91-2320-B-040-023).European Journal of Clinical Nutrition (2004) 58, 481-487. doi:10.1038/sj.ejcn.1601834 [ABSTRACT FROM AUTHOR]

High-temperature threshold characteristics of a symmetrically graded δ-doped InAlAs/InxGa1-xAs/GaAs (x=0.5→0.65→0.5) metamorphic high electron mobility transistor (MHEMT) have been investigated. The thermal threshold coefficients, defined as ∂Vth/∂T, are superiorly low at 0.9 mV/K from 300 to 420 K and at -0.75 mV/K from 420 to 500 K. An interesting polarity change of the thermal threshold coefficient was observed around 420 K due to the variation of thermal modulation effects. The present MHEMT device, with stabilized thermal threshold variations and superior high-temperature linearity characteristics, is promising for high-temperature circuit applications. [ABSTRACT FROM AUTHOR]

The plasmon resonance of Au/SiO2 multilayered nanodisks was studied using light scattering spectroscopy and numerical calculations. Compared to single layered Au nanodisks, multilayered nanodisks exhibit several distinctive properties including significantly enhanced plasmon resonances and tunable resonance wavelengths which can be tailored to desired values by simply varying dielectric layer thickness while the particle diameter is kept constant. Numerical calculations show that slicing one metal layer into metal multilayers leads to higher scattering intensity and more “hot spots,” or regions of strong field enhancement. This tunable and augmented plasmon resonance holds a great potential in the applications of surface-enhanced Raman scattering (SERS). [ABSTRACT FROM AUTHOR]