Angiopoietin-2 confers Atheroprotection in apoE-/- mice by inhibiting LDL oxidation via nitric oxide

Atherosclerosis is promoted by a combination of hypercholesterolemia and vascular inflammation. The function of Angiopoietin (Ang)-2, a key regulator of angiogenesis, in the maintenance of large vessels is unknown. A single systemic administration of Ang-2 adenovirus (AdAng-2) to apoE-/- mice fed a Western diet significantly reduced atherosclerotic lesion size 8 40%) and oxidized LDL and macrophage content of the plaques. These beneficial effects were abolished by the inhibition of nitric oxide synthase (NOS). In endothelial cells, endothelial NOS activation per se inhibited LDL oxidation and Ang-2 stimulated NO release in a Tie2-dependent manner to decrease LDL oxidation. These findings demonstrate a novel atheroprotective role for Ang-2 when endothelial cell function is compromised and suggest that growth factors, which stimulate NO release without inducing inflammation, could offer atheroprotection.

Comprehensive process maps for synthesizing high density aluminum oxide-carbon nanotube coatings by plasma spraying for improved mechanical and wear properties

Plasma sprayed aluminum oxide ceramic coating is widely used due to its outstanding wear, corrosion, and thermal shock resistance. But porosity is the integral feature in the plasma sprayed coating which exponentially degrades its properties. In this study, process maps were developed to obtain Al2O3-CNT composite coatings with the highest density (i.e. lowest porosity) and improved mechanical and wear properties. Process map is defined as a set of relationships that correlates large number of plasma processing parameters to the coating properties. Carbon nanotubes (CNTs) were added as reinforcement to Al2O 3 coating to improve the fracture toughness and wear resistance. Two novel powder processing approaches viz spray drying and chemical vapor growth were adopted to disperse CNTs in Al2O3 powder. The degree of CNT dispersion via chemical vapor deposition (CVD) was superior to spray drying but CVD could not synthesize powder in large amount. Hence optimization of plasma processing parameters and process map development was limited to spray dried Al2O3 powder containing 0, 4 and 8 wt. % CNTs. An empirical model using Pareto diagram was developed to link plasma processing parameters with the porosity of coating. Splat morphology as a function of plasma processing parameter was also studied to understand its effect on mechanical properties. Addition of a mere 1.5 wt. % CNTs via CVD technique showed ∼27% and ∼24% increase in the elastic modulus and fracture toughness respectively. Improved toughness was attributed to combined effect of lower porosity and uniform dispersion of CNTs which promoted the toughening by CNT bridging, crack deflection and strong CNT/Al2O3 interface. Al2O 3-8 wt. % CNT coating synthesized using spray dried powder showed 73% improvement in the fracture toughness when porosity reduced from 4.7% to 3.0%. Wear resistance of all coatings at room and elevated temperatures (573 K, 873 K) showed improvement with CNT addition and decreased porosity. Such behavior was due to improved mechanical properties, protective film formation due to tribochemical reaction, and CNT bridging between the splats. Finally, process maps correlating porosity content, CNT content, mechanical properties, and wear properties were developed.

Tin oxide based composites derived using electrostatic spray deposition technique as anodes for lithium-ion batteries

Recent advances in the electric & hybrid electric vehicles and rapid developments in the electronic devices have increased the demand for high power and high energy density lithium ion batteries. Graphite (theoretical specific capacity: 372 mAh/g) used in commercial anodes cannot meet these demands. Amorphous SnO2 anodes (theoretical specific capacity: 781 mAh/g) have been proposed as alternative anode materials. But these materials have poor conductivity, undergo a large volume change during charging and discharging, large irreversible capacity loss leading to poor cycle performances. To solve the issues related to SnO2 anodes, we propose to synthesize porous SnO2 composites using electrostatic spray deposition technique. First, porous SnO2/CNT composites were fabricated and the effects of the deposition temperature (200, 250, 300 °C) & CNT content (10, 20, 30, 40 wt %) on the electrochemical performance of the anodes were studied. Compared to pure SnO2 and pure CNT, the composite materials as anodes showed better discharge capacity and cyclability. 30 wt% CNT content and 250 °C deposition temperature were found to be the optimal conditions with regard to energy capacity whereas the sample with 20% CNT deposited at 250 °C exhibited good capacity retention. This can be ascribed to the porous nature of the anodes and the improvement in the conductivity by the addition of CNT. Electrochemical impedance spectroscopy studies were carried out to study in detail the change in the surface film resistance with cycling. By fitting EIS data to an equivalent circuit model, the values of the circuit components, which represent surface film resistance, were obtained. The higher the CNT content in the composite, lower the change in surface film resistance at certain voltage upon cycling. The surface resistance increased with the depth of discharge and decreased slightly at fully lithiated state. Graphene was also added to improve the performance of pure SnO2 anodes. The composites heated at 280 °C showed better energy capacity and energy density. The specific capacities of as deposited and post heat-treated samples were 534 and 737 mAh/g after 70 cycles. At the 70th cycle, the energy density of the composites at 195 °C and 280 °C were 1240 and 1760 Wh/kg, respectively, which are much higher than the commercially used graphite electrodes (37.2–74.4 Wh/kg). Both SnO2/CNTand SnO2/grapheme based composites with improved energy densities and capacities than pure SnO2 can make a significant impact on the development of new batteries for electric vehicles and portable electronics applications.

Preservation of nitric oxide availability as nitrite and nitrosothiols

Nitric Oxide (NO) has been known for long to regulate vessel tone. However, the close proximity of the site of NO production to "sinks" of NO such as hemoglobin (Hb) in blood suggest that blood will scavenge most of the NO produced. Therefore, it is unclear how NO is able to play its physiological roles. The current study deals with means by which this could be understood. Towards studying the role of nitrosothiols and nitrite in preserving NO availability, a study of the kinetics of glutathione (GSH) nitrosation by NO donors in aerated buffered solutions was undertaken first. Results suggest an increase in the rate of the corresponding nitrosothiol (GSNO) formation with an increase in GSH with a half-maximum constant EC50 that depends on NO concentration, thus indicating a significant contribution of NO2 mediated nitrosation in the production of GSNO. Next, the ability of nitrite to be reduced to NO in the smooth muscle cells was evaluated. The NO formed was inhibited by sGC inhibitors and accelerated by activators and was independent of O2 concentration. Nitrite transport mechanisms and effects of exogenous nitrate on transport and reduction of nitrite were examined. The results showed that sGC can mediate nitrite reduction to NO and nitrite is transported across the smooth muscle cell membrane via anion channels, both of which can be attenuated by nitrate. Finally, a 2-D axisymmetric diffusion model was constructed to test the accumulation of NO in the smooth muscle layer from reduction of nitrite. It was observed that at the end of the simulation period with physiological concentrations of nitrite in the smooth muscle cells (SMC), a low sustained NO generated from nitrite reduction could maintain significant sGC activity and might affect vessel tone. The major nitrosating mechanism in the circulation at reduced O2 levels was found to be anaerobic and a Cu+ dependent GSNO reduction activity was found to deliver minor amounts of NO from physiological GSNO levels in the tissue.

Diametrically opposed actions of the heme oxygenase-1 and endothelial nitric oxide synthase pathways in angiogenesis via p21WAF1

INTRODUCTION: Vascular endothelial growth factor (VEGF)-induced angiogenesis requires endothelial nitric oxide synthase (eNOS) activation, however, the mechanism is largely unknown. As nitric oxide(NO) inhibits endothelial proliferation to promote capillary formation (Am J Path,159:993-1008,2001) and p21WAF1 is an important cell cycle inhibitor, we hypothesised that eNOS-induced angiogenesis requires up regulation of p21WAF1. METHODS: Human and porcine endothelial cells were cultured on growth factor reduced Materigel for in vitro tube formation and in vivo angiogenesis was assessed by hind limb ligation ischemia model.Conversely, we propose that the cytoprotective enzyme, heme oxygenase-1(HO-1), may suppress p21WAF1 to limit angiogenesis. RESULTS: The expression of p21WAF1 was up regulated in porcine aorticenothelial cells stablely transfected with a constitutively activated form of eNOS (eNOSS1177D) as well as in HUVEC infected by adenovirus encoding eNOSS1177D. When these cells were plated on growth-factor reduced Matrigel (compaired to empty vector), they enhanced in vitro angiogenesis, which was inhibited following knockdown of p21WAF1. Furthermore, over expression of p21WAF1 led to increased tube formation while p21WAF1 knockdown abrogated vascular endothelial growth factor(VEGF) and fibroblast growth factor (FGF-2) mediated angiogenesis.Conversely, the cytoprotective enzyme, heme oxygenase-1 (HO-1) when over expressed decreased p21WAF1 expression and reduced VEGF, FGF-2 and eNOSS1177D-induced angiogenesis. CONCLUSIONS: These results demonstrate that eNOS-induced angiogenesis requires up regulation of p21WAF1/CIP1 wherease, induction of HO-1 will decrease the expression of p21WAF1/CIP1 to limit angiogenesisindicating that eNOS and HO-1 regulate angiogenesis via p21WAF1/CIP1 in adiametrically opposed manner and that p21WAF1/CIP1 appears to be a central regulator of angiogenesis that offers a new therapeutic target.

Effects of alternating current voltage amplitude and oxide capacitance on mid-gap interface state defect density extractions in In0.53Ga 0.47As capacitors

This work looks at the effect on mid-gap interface state defect density estimates for In0.53Ga0.47As semiconductor capacitors when different AC voltage amplitudes are selected for a fixed voltage bias step size (100 mV) during room temperature only electrical characterization. Results are presented for Au/Ni/Al2O3/In0.53Ga0.47As/InP metal–oxide–semiconductor capacitors with (1) n-type and p-type semiconductors, (2) different Al2O3 thicknesses, (3) different In0.53Ga0.47As surface passivation concentrations of ammonium sulphide, and (4) different transfer times to the atomic layer deposition chamber after passivation treatment on the semiconductor surface—thereby demonstrating a cross-section of device characteristics. The authors set out to determine the importance of the AC voltage amplitude selection on the interface state defect density extractions and whether this selection has a combined effect with the oxide capacitance. These capacitors are prototypical of the type of gate oxide material stacks that could form equivalent metal–oxide–semiconductor field-effect transistors beyond the 32 nm technology node. The authors do not attempt to achieve the best scaled equivalent oxide thickness in this work, as our focus is on accurately extracting device properties that will allow the investigation and reduction of interface state defect densities at the high-k/III–V semiconductor interface. The operating voltage for future devices will be reduced, potentially leading to an associated reduction in the AC voltage amplitude, which will force a decrease in the signal-to-noise ratio of electrical responses and could therefore result in less accurate impedance measurements. A concern thus arises regarding the accuracy of the electrical property extractions using such impedance measurements for future devices, particularly in relation to the mid-gap interface state defect density estimated from the conductance method and from the combined high–low frequency capacitance–voltage method. The authors apply a fixed voltage step of 100 mV for all voltage sweep measurements at each AC frequency. Each of these measurements is repeated 15 times for the equidistant AC voltage amplitudes between 10 mV and 150 mV. This provides the desired AC voltage amplitude to step size ratios from 1:10 to 3:2. Our results indicate that, although the selection of the oxide capacitance is important both to the success and accuracy of the extraction method, the mid-gap interface state defect density extractions are not overly sensitive to the AC voltage amplitude employed regardless of what oxide capacitance is used in the extractions, particularly in the range from 50% below the voltage sweep step size to 50% above it. Therefore, the use of larger AC voltage amplitudes in this range to achieve a better signal-to-noise ratio during impedance measurements for future low operating voltage devices will not distort the extracted interface state defect density.

Lead oxide-modified TiO2 photocatalyst: tuning light absorption and charge carrier separation by lead oxidation state

Modification of TiO2 with metal oxide nanoclusters such as FeOx, NiOx has been shown to be a promising approach to the design of new photocatalysts with visible light absorption and improved electron–hole separation. To study further the factors that determine the photocatalytic properties of structures of this type, we present in this paper a first principles density functional theory (DFT) investigation of TiO2 rutile(110) and anatase(001) modified with PbO and PbO2 nanoclusters, with Pb2+ and Pb4+ oxidation states. This allows us to unravel the effect of the Pb oxidation state on the photocatalytic properties of PbOx-modified TiO2. The nanoclusters adsorb strongly at all TiO2 surfaces, creating new Pb–O and Ti–O interfacial bonds. Modification with PbO and PbO2 nanoclusters introduces new states in the original band gap of rutile and anatase. However the oxidation state of Pb has a dramatic impact on the nature of the modifications of the band edges of TiO2 and on the electron–hole separation mechanism. PbO nanocluster modification leads to an upwards shift of the valence band which reduces the band gap and upon photoexcitation results in hole localisation on the PbO nanocluster and electron localisation on the surface. By contrast, for PbO2 nanocluster modification the hole will be localised on the TiO2 surface and the electron on the nanocluster, thus giving rise to two different band gap reduction and electron–hole separation mechanisms. We find no crystal structure sensitivity, with both rutile and anatase surfaces showing similar properties upon modification with PbOx. In summary the photocatalytic properties of heterostructures of TiO2 with oxide nanoclusters can be tuned by oxidation state of the modifying metal oxide, with the possibility of a reduced band gap causing visible light activation and a reduction in charge carrier recombination.

Growth, Characterization, and Properties of Hybrid Graphene-Carbon Nanotube Films and Related Carbon Nanostructures

Graphene, first isolated in 2004 and the subject of the 2010 Nobel Prize in physics, has generated a tremendous amount of research interest in recent years due to its incredible mechanical and electrical properties. However, difficulties in large-scale production and low as-prepared surface area have hindered commercial applications. In this dissertation, a new material is described incorporating the superior electrical properties of graphene edge planes into the high surface area framework of carbon nanotube forests using a scalable and reproducible technology.

The objectives of this research were to investigate the growth parameters and mechanisms of a graphene-carbon nanotube hybrid nanomaterial termed “graphenated carbon nanotubes” (g-CNTs), examine the applicability of g-CNT materials for applications in electrochemical capacitors (supercapacitors) and cold-cathode field emission sources, and determine materials characteristics responsible for the superior performance of g-CNTs in these applications. The growth kinetics of multi-walled carbon nanotubes (MWNTs), grown by plasma-enhanced chemical vapor deposition (PECVD), was studied in order to understand the fundamental mechanisms governing the PECVD reaction process. Activation energies and diffusivities were determined for key reaction steps and a growth model was developed in response to these findings. Differences in the reaction kinetics between CNTs grown on single-crystal silicon and polysilicon were studied to aid in the incorporation of CNTs into microelectromechanical systems (MEMS) devices. To understand processing-property relationships for g-CNT materials, a Design of Experiments (DOE) analysis was performed for the purpose of determining the importance of various input parameters on the growth of g-CNTs, finding that varying temperature alone allows the resultant material to transition from CNTs to g-CNTs and finally carbon nanosheets (CNSs): vertically oriented sheets of few-layered graphene. In addition, a phenomenological model was developed for g-CNTs. By studying variations of graphene-CNT hybrid nanomaterials by Raman spectroscopy, a linear trend was discovered between their mean crystallite size and electrochemical capacitance. Finally, a new method for the calculation of nanomaterial surface area, more accurate than the standard BET technique, was created based on atomic layer deposition (ALD) of titanium oxide (TiO2).

Reconfigurable UWB Filtennas with Dual Bandnotch for Unwanted Bands using Graphene based Switches

Presented are the design and results of a reconfigurable UWB filtenna with sharp dual bandnotch at WiMAX 3.5 GHz and WLAN 5.8 GHz bands. The filtenna is formed by placing three loop resonators in an UWB antenna. The resonators are fitted with Graphene based switches which introduce reconfigurability. The filtenna was simulated electromagnetically and with Graphene based switches in switches OFF and switches ON states. Presented results show a passband from 2.81–12.27 GHz in OFF state and ON state results in sharp dual bandnotch within the passband at 3.45 and 5.95 GHz at a return loss of 2–2.5 dB. The gain and efficiency in both states has also been given and is reduced in ON state at the dual bandnotch. The radiation patterns in E- and H-planes are stable.

Quantification of glycine betaine, choline and trimethylamine N-oxide in seawater particulates: Minimisation of seawater associated ion suppression

A liquid chromatography/mass spectrometry (LC/MS, electrospray ionisation) method has been developed for the quantification of nitrogenous osmolytes (N-osmolytes) in the particulate fraction of natural water samples. Full method validation demonstrates the validity of the method for measuring glycine betaine (GBT), choline and trimethylamine N-oxide (TMAO) in particulates from seawater. Limits of detection were calculated as 3.5, 1.2 and 5.9 pg injected onto column (equivalent to 1.5, 0.6 and 3.9 nmol per litre) for GBT, choline and TMAO respectively. Precision of the method was typically 3% for both GBT and choline and 6% for TMAO. Collection of the particulate fraction of natural samples was achieved via in-line filtration. Resulting chromatography and method sensitivity was assessed and compared for the use of both glass fibre and polycarbonate filters during sample collection. Ion suppression was shown to be a significant cause of reduced instrument response to N-osmolytes and was associated with the presence of seawater in the sample matrix

Quantification of glycine betaine, choline and trimethylamine N-oxide in seawater particulates: Minimisation of seawater associated ion suppression

A liquid chromatography/mass spectrometry (LC/MS, electrospray ionisation) method has been developed for the quantification of nitrogenous osmolytes (N-osmolytes) in the particulate fraction of natural water samples. Full method validation demonstrates the validity of the method for measuring glycine betaine (GBT), choline and trimethylamine N-oxide (TMAO) in particulates from seawater. Limits of detection were calculated as 3.5, 1.2 and 5.9 pg injected onto column (equivalent to 1.5, 0.6 and 3.9 nmol per litre) for GBT, choline and TMAO respectively. Precision of the method was typically 3% for both GBT and choline and 6% for TMAO. Collection of the particulate fraction of natural samples was achieved via in-line filtration. Resulting chromatography and method sensitivity was assessed and compared for the use of both glass fibre and polycarbonate filters during sample collection. Ion suppression was shown to be a significant cause of reduced instrument response to N-osmolytes and was associated with the presence of seawater in the sample matrix

A simply effective double-coating cathode with MnO2 nanosheets/graphene as functionalized interlayer for high performance lithium-sulfur batteries

Herein, we report a facile and effective adsorption strategy to improve the performance of Lithium-Sulfur (Li-S) batteries. MnO₂ nanosheets grown on the surface of highly conductive graphene resulted in a coupled composite bilayer electrode when coated onto a sulfur cathode. In this way, a high initial specific capacity of 1395 mA h g^-1 at a rate of 0.5C, a coulombic efficiency approaching 100% and steady cyclic efficiency with a fade rate of 0.3% per cycle from 10 to 100 cycles has been achieved. This hybrid electrode not only shows enhanced electrochemical performance but can also be easily controlled and scaled thereby aiding future commercialization of high-performance Li-S batteries.

Effect of nitric oxide donors on blood pressure and pulse pressure in acute and subacute stroke

High blood pressure (BP), pulse pressure (PP), and rate pressure product (RPP) areeach associated independently with a poor outcome in acute ischemic stroke. Whereas nitric oxide (NO) donors, such as glyceryl trinitrate (GTN), lower blood pressure in acute ischemic stroke, their effect on other hemodynamic measures is not known. We performed a systematic review of the effects of NO donors on systemic hemodynamic measures in patients with acute/subacute stroke. Randomized controlled trials were identified from searches of the Cochrane Library, Pubmed, and Embase. Information on hemodynamic measures, including systolic BP (SBP), diastolic BP (DBP), and heart rate, were assessed, and hemodynamic derivatives of these were calculated: PP (PP SBP DBP), mean arterial pressure (MAP DBP PP/3), mid blood pressure (MBP (SBP DBP)/2), pulse pressure index (PPI PP/MAP), and RPP (RPP SBP HR). The effect of treatment on hemodynamic measures was calculated as the weighted mean difference (WMD) between treated and control groups with adjustment for baseline. Results: Three trials involving 145 patients were identified; 93 patients received the NO donor, GTN, and 52 control. As compared with placebo, GTN significantly reduced SBP (WMD -9.80 mmHg, p< 0.001), DBP (WMD -4.43 mmHg, p<0.001), MAP (WMD -6.41 mmHg, p< 0.001), MBP (WMD -7.33 mmHg,p<0.001), PP (WMD -6.11 mmHg, p<0.001 ) and PPI (WMD -0.03, p=0.04 ). 3 GTN increased HR (WMD +3.87 bpm, p<0.001) and non-significantly lowered RPP (WMD -323 mmHg.bpm, p=0.14). Conclusion: The NO donor GTN reduces BP, PP and other derivatives in acute and subacute stroke whilst increasing heart rate.

Nitric oxide synthase and NAD(P)H oxidase modulate coronary endothelial cell growth

Reactive oxygen species (ROS) including nitric oxide (NO) and superoxide anion (O2-) are associated with cell migration, proliferation and many growth-related diseases. The objective of this study was to determine whether there was a reciprocal relationship between rat coronary microvascular endothelial cell (CMEC) growth and activity/expressions (mRNA and protein) of endothelial NO synthase (eNOS) and NAD(P)H oxidase enzymes. Proliferating namely, 50% confluent CMEC possessed approximately three-fold increased activity and expression of both enzymes compared to 100% confluent cells. Treatment of CMEC with an inhibitor of eNOS (L-NAME, 100M) increased cell proliferation as assessed via three independent methods i.e. cell counting, determination of total cellular protein levels and [3H]thymidine incorporation. Similarly, treatment of CMEC with pyrogallol (0.3-3 mM), a superoxide anion (O2-)- generator, also increased CMEC growth while spermine NONOate (SpNO), a NO donor, significantly reduced cell growth. Co-incubation of CMEC with a cell permeable superoxide dismutase mimetic (Mn-III-tetrakis-4-benzoic acid-porphyrin; MnTBAP) plus either pyrogallol or NO did not alter cell number and DNA synthesis thereby dismissing the involvement of peroxynitrite (OONO-) in CMEC proliferation. Specific inhibitors of NAD(P)H oxidase but not other ROS-generating enzymes including cyclooxygenase and xanthine oxidase, attenuated cell growth. Transfection of CMEC with antisense p22-phox cDNA, a membrane-bound component of NAD(P)H oxidase, resulted in substantial reduction in [3H]thymidine incorporation, total cellular protein levels and expression of p22-phox protein. These data demonstrate a cross-talk between CMEC growth and eNOS and NAD(P)H oxidase enzyme activity and expression, thus suggesting that the regulation of these enzymes may be critical in preventing the initiation and/or progression of coronary atherosclerosis.

Manufacturing conditioned roughness and wear of biomedical oxide ceramics for all-ceramic knee implants

Background: Ceramic materials are used in a growing proportion of hip joint prostheses due to their wear resistance and biocompatibility properties. However, ceramics have not been applied successfully in total knee joint endoprostheses to date. One reason for this is that with strict surface quality requirements, there are significant challenges with regard to machining. High-toughness bioceramics can only be machined by grinding and polishing processes. The aim of this study was to develop an automated process chain for the manufacturing of an all-ceramic knee implant. Methods: A five-axis machining process was developed for all-ceramic implant components. These components were used in an investigation of the influence of surface conformity on wear behavior under simplified knee joint motion. Results: The implant components showed considerably reduced wear compared to conventional material combinations. Contact area resulting from a variety of component surface shapes, with a variety of levels of surface conformity, greatly influenced wear rate. Conclusions: It is possible to realize an all-ceramic knee endoprosthesis device, with a precise and affordable manufacturing process. The shape accuracy of the component surfaces, as specified by the design and achieved during the manufacturing process, has a substantial influence on the wear behavior of the prosthesis. This result, if corroborated by results with a greater sample size, is likely to influence the design parameters of such devices.