bluuebunny/crossref_metadata_2025 huggingface dataset:
Residual Stress and Buckling Patterns of Yttria-Stabilised-Zirconia Thin Films for Micro-Solid Oxide Fuel Cell Membranes
Authors: Evans Anna , Prestat Michel , Tölke René , Gauckler Ludwig J. , Hocker Thomas , Safa Yasser , Briand Danick , Courbat Jérôme , De Rooij Nico
Published: April 2012

Free-standing yttria-stabilised-zirconia (YSZ) thin films can be found in today's miniaturised gas sensors and as electrolytes in micro-solid oxide fuel cell membranes. 8 mol.% YSZ thin films prepared by pulsed laser deposition on silicon substrates are investigated by wafer curvature and nanoindentation. The 300nm thin 8YSZ films deposited at 700°C have a compressive stress of -1100±150 MPa and a Young's modulus of 205±20 GPa at 25 °C. The corresponding free-standing 8YSZ membranes are investigated by light microscopy and white light interferometry. The 8YSZ membranes deposited at 700°C have a buckling shape with a C4z-rotational symmetry and buckling amplitude of 6.5μm at 25°C. Numerical simulations of the buckling patterns using the Rayleigh-Ritz-method are in good agreement with the experimental data. These simulated buckling patterns are used to extract the local stress distribution. This is important regarding the application of YSZ membranes in micro-solid oxide fuel cells which must be thermomechanically-stable during device operation.
Effect of Sintering Aids on the Stress Evolution of Constrained Sintered Gadolinium-Doped Ceria Films
Authors: Nicholas Jason D. , Mandowara Sunil , Yang Qing , Sheldon Brian W.
Published: April 2012

The in situ stress evolution of constrained Ce0.9Gd0.1O1.95 (CGO) porous thick films containing no sintering aids, 3 mol% lithium, or 3 mol% cobalt were measured from 25-1040C in air. The addition of 3 mol% lithium facilitated relaxation of the 1040C constrained sintering stress, and raised the sintered film relative density from 59 ± 5% (for pure CGO) to 85 ± 5%. In contrast, the addition of 3 mol% cobalt did not facilitate relaxation of the 1040C constrained sintering stress, and only raised the sintered film relative density to 64 ± 5%. This is surprising because both lithium and cobalt at the 3 mol% doping level are effective unconstrained CGO sintering aids (reducing the sintering temperature from ~1400C to ~800C and ~1000C, respectively). These results are consistent with cobalt enhancing solid-state diffusion and lithium inducing liquid phase sintering. Anomalous, low-temperature tensile stresses were also observed for films of all three compositions.
(Invited) High-Performance Direct Ethanol Solid Oxide Fuel Cells
Authors: Armstrong Eric N. , Park Jae-Woo , Minh Nguyen Q.
Published: April 2012

An anode supported solid oxide fuel cell (SOFC)with a dual layer anode consisting of a Cu-ceria impregnated Ni-yttria stabilized zirconia (YSZ) support outer layer and a Ni-YSZ electroactive inner layer was investigated for the direct operation on ethanol. High electrochemical performance without evidence of anode coking was demonstrated at 800C in short term tests. A peak power density of about 400 mW/cm2 was obtained with 7.3% ethanol balance He fuel and air oxidant.
Redox Stability of Ni-YSZ Cermets Prepared by Polymeric Precursor Infiltration
Authors: Buyukaksoy Aligul , Petrovksy Vladimir , Dogan Fatih
Published: April 2012

Redox stability of anodes is one of the important challenges in SOFC design. It is well known that co-sintered Ni-YSZ cermets usually used as anodes in SOFCs degrade rapidly during redox cycling. A possible solution of this problem is the utilization of infiltration technique for the processing of Ni-YSZ cermet, which showed promising results towards development of redox stable anodes. Pre-sintered porous YSZ layers were first infiltrated with YSZ polymeric precursor followed by infiltration of a NiO polymeric precursor. This unique double infiltration process practically eliminated the degradation of Ni-YSZ cermet during redox cycling at temperatures as high as 800oC.
Fabrication and Evaluation of Micro-Tubular SOFC Stack
Authors: Yamaguchi Toshiaki , Sumi Hirofumi , Suzuki Toshio , Fujishiro Yoshinobu
Published: April 2012

We developed a fabrication processes of a micro-tubular SOFC stack using a metallic tubular interconnect. The stack was made of the 12 micro-tubular cells, which were connected in series. The open circuit voltage (OCV) was above 13V, thus the single cell showed the OCV value about 1.1V. Fuel utilization of the stack under a wet H2 flow of 20cc/min was above 90%, and the efficiency (LHV) was about 60%. In addition, the stack can be started-up within 5 min, and we succeeded the quick-start/shut down multi-cycles.
Electrochemical Promotion of Propane Combustion on Highly Dispersed Pt Nanoparticles
Authors: Kambolis Anastasios , Lizarraga Leonardo , Tsampas Michalis N. , Rieu Mathilde , Viricelle Jean-Paul , Vernoux Philippe
Published: April 2012

Pt nanoparticles, in a size range which varies from 3 to 20 nm, were dispersed in the porosity of a 7.5 µm-thick layer of LSCF-GDC electrode interfaced on a dense GDC membrane. Small positive polarizations (200 µA / 0.8V - 1.2V) can strongly increase the Pt nanoparticles catalytic performance for propane deep oxidation at low temperatures (267°C-338°C). 40%-enhancement of the propane conversion was achieved with apparent Faraday efficiency values up to 85. These results clearly demonstrate that metallic nanoparticles dispersed in the porosity of a mixed ionic electronic conducting electrode can be electropromoted.
High-Performance Broadband Gallium Nitride (GaN) Power Amplifiers for Next Generation Communication Applications
Authors: Shenai Krishna , Leong S. K.
Published: April 2012

Broadband Gallium Nitride (GaN) power amplifiers (PAs) capable of delivering more than >150W of continuous power at 2GHz with an efficiency >70% are reported. The measured third-order intermodulation (IM3) signal amplitude is <-35dBc over the frequency range from 225MHz to 2GHz. Further improvement in communication performance is feasible with improved device design and thermal management.
GaN Power Schottky Diodes
Authors: Tompkins Randy P. , Smith Joshua R. , Zhou Shuai , Kirchner Kevin W. , Derenge Michael A. , Jones Kenneth A. , Leach Jacob H. , Mulholland Greg , Udwary Kevin , Preble Edward , Suvarna Puneet , Tungare Mihir , Shahedipour-Sandvik F.
Published: April 2012

Metalorganic Chemical Vapor Deposition (MOCVD) GaN films were grown simultaneously on multiple substrates ranging in threading dislocation density from 10^3 to 10^10 cm^-2. GaN power Schottky diodes were fabricated on these films to examine the role of crystalline defects on the performance of these devices. For films grown on each of the four substrates, the breakdown voltages did not approach the theoretical limit of ≈ 1600 V. This was an unexpected result, in particular for films grown on the truly bulk GaN which demonstrated superior crystallinity as indicated by x-ray diffraction. We speculate that point defects, possibly carbon, are playing a role in the performance of these devices.
Design, Fabrication, Characterization, and Evaluation of X-ray Detectors Based on n-type 4H-SiC Epitaxial Layer
Authors: Mandal Krishna C. , Muzykov Peter G. , Terry J. Russell
Published: April 2012

The Schottky barrier diode (SBD) radiation detectors on n-type 4H-SiC epitaxial layer have been designed, fabricated, and evaluated for low energy x-rays detection. The detectors were found to be highly sensitive to x-ray flux in the 50 eV to few keV range and showed significantly improved response compared to the commercial of-the-shelf (COTS) SiC UV photodiodes. Thermally stimulated current (TSC) measurements performed in wide temperature range (94 - 550 K) revealed low density of deep level centers in the epitaxial layer. The high quality of the epitaxial layer was confirmed by XRD rocking curve measurements and defect delineating chemical etching. The detectors fabricated on 4H-SiC epitaxial layers exhibited low leakage current at 475 K (< 1 nA at 200 V) revealing great possibility of high temperature operation.
Structure and Photoluminescence of Metal Oxide Core-Shell Nanowire Arrays
Authors: Thomas M. Allan , Cui Jingbiao , Watanabe Fumiya
Published: April 2012

Metal oxide core-shell nanowire arrays composed of electrodeposited ZnO nanowires and atomic layer deposited Al2O3, ZnO, and TiO2 shells were fabricated at low process temperatures. The structural and photoluminescence (PL) properties of the core-shell structures were investigated and distinctive features were induced by the shell coatings. Due in part to their low temperature deposition, the effects of annealing on the core-shell nanowires were also studied in detail. The room temperature and low temperature PL of the nanowire cores are affected by the annealing treatments and the shell layers, with diverse effects observed depending on the shell material. Evidence for solid state reactions between the ZnO core and metal-oxide shell at increased annealing temperatures was also observed, leading to further changes in their optical properties.
Core-Shell ZnO Nanorod Lasers
Authors: Visimberga G. , Faulkner C. C. , Boese M. , O'Dwyer C.
Published: April 2012

Room-temperature ultraviolet lasing in [0001] oriented zinc oxide nanorods grown on silicon and fused silica substrates by a simple vapor transport and condensation process. These wide band-gap semiconductor nanorods form natural laser cavities with diameters varying from 150 to 350 nm and lengths up to 10 µm. Under optical excitation, surface-emitting lasing action was observed at 385 nm. The dielectric core-shell Al2O3@ZnO nanorods exhibit enhanced axial Fabry-Pérot resonating characteristics with (0001) crystal faces as mirror facets improved by a metallic reflector at one end. This metallic coating and dielectric oxide shell greatly increase near-band edge emission while reducing excitation power thresholds due to lower losses and increased optical density from improved refractive index mediated waveguiding during optical pumping.
Superatmospheric MOCVD Reactor Design for High Quality InGaN Growth
Authors: Melton Andrew G. , Davis Phill , Uddin Mesbah , Stokes E. B.
Published: April 2012

The MOCVD epitaxy technique is typically performed at sub-atmospheric pressures, however there is evidence suggesting that the crystalline quality of InGaN thin films could be improved by growing at super-atmospheric pressure. Toward this goal, computational fluid dynamics techniques have been used to design a vertical, rotating-susceptor MOCVD chamber capable of growth pressures up to 3 atm. Flow instabilities arising from the heated, rotating susceptor have been minimized by changing the shape of the transition curve of the reactor.
Healing of Surface States and Point Defects in Single-Crystalline β-Ga2O3 Epilayer
Authors: Ravadgar Parvaneh , Horng Ray-Hua , Wang T. Y.
Published: April 2012

Single-crystalline β-Ga2O3 epilayer on (0001) sapphire was grown at low temperature and low pressure by MOCVD. The as-grown β-Ga2O3 epilayer was annealed at 800 ºC in atmosphere. Crystal structure and quality of the epilayer remained the same after annealing. Influence of surface states and point defects of β-Ga2O3 epilayers before and after annealing are studied using room-temperature Photoluminescence (PL) and I-V characteristics. The significant difference in PL property of β-Ga2O3 and big difference (~5 orders in magnitude) in dark current before and after annealing is attributed to the healing of the surface states and point defects. Gallium oxide is known for its high density of oxygen vacancies. Annealing single-crystalline β-Ga2O3 epilayer at high temperature makes the healing possible, probably due to oxygen adsorption. A significant healing of surface states and point defects in single-crystalline β-Ga2O3 indicates its high potential in fabrication of optoelectronic devices.
The Effects of an O2 Plasma on the Optical Properties of Atomic Layer Deposited ZnO
Authors: Thomas M. Allan , Cui Jingbiao
Published: April 2012

The optical properties of atomic layer deposited (ALD) ZnO thin films were explored in detail. A plasma enhanced-ALD process using diethlyzinc and a remote O2 plasma as well as a plasma enhanced thermal-ALD method in which a remote O2 plasma step is added after each cycle of the classic thermal-ALD process were investigated. The optical properties of the films were found to depend strongly on the ALD process and plasma conditions. Absorption and room temperature photoluminescence (PL) measurements indicate both the bandgap and defect concentrations in the ZnO films are affected by the plasma. The low temperature PL characteristics of the films are also affected by the plasma, providing further evidence that it has distinct effects on the growth process and in turn ZnO material properties.
Investigating Degradation Behavior of InGaZnO Thin-Film Transistors Induced by Charge-Trapping Effect under DC and AC Gate-Bias Stress
Authors: Hsieh Tien-Yu , Chang Ting-Chang , Chen Te-Chih , Tsai Ming-Yen , Chen Yu-Te , Jian Fu-Yen
Published: April 2012

This paper investigates the degradation mechanism of amorphous InGaZnO thin-film transistors under DC and AC gate bias stress. Comparing the degradation behavior at equal accumulated effective stress time, more pronounced threshold voltage shift under AC positive gate bias stress in comparison with DC stress indicates extra electron-trapping phenomenon occurs during the duration of rising/falling time in pulse. Contrarily, illuminated AC negative gate bias stress exhibits much less threshold voltage shift than DC stress, which suggesting the photo-generated hole does not has sufficient time to drift to the interface of IGZO/gate insulator and causes hole-trapping under AC operation. Since the evolution of threshold voltage fits the stretched-exponential equation well, the different degradation tendencies under DC/AC stress can be attributed to the different electron- and hole-trapping efficiencies, and this is further verified by varying pulse waveform.
Cu(In,Ga)Se2 Thin Films Preparation from CuGa-In Metallic Alloy and Se Thin Film by Atmosphere Pressure Plasma Depositon System
Authors: Chang Kow-Ming , Ho Po Ching , Yang Kuo-Hui , Wu Shen-Bin , Liu Chi-Hung
Published: April 2012

An atmosphere pressure plasma (APP) deposition system with dielectric barrier discharge (DBD) is proposed for deposition selenium thin films. Several advantages of the APP deposition system are low cost, high processing speed and its potential to be applied in roll-to-roll process. Morphologies and thicknesses of selenium thin films deposited on In/CuGa/Mo/SLG can be affected by plasma power which also has impact on crystallinity of CIGS absorber. With the increase in plasma power, CIGS grains tend to distribute non-uniformly. Plasma power of 100W has the smallest FWHM of the main peak (112). Insufficient selenium incorporation into precursors result in undesired phases such as Cu3Se2, Cu2Se and separation phase, CuGaSe2 ¬compound. Compositions of optimal selenized CIGS thin film deposited by scanning 180 times are Cu/(In+Ga) = 1.03 and Ga/(In+Ga) = 0.24.
Deposition and Characterization of Low-Cost Spray Pyrolyzed Cu2ZnSnS4 (CZTS) Thin-Films for Large-Area High-Efficiency Heterojunction Solar Cells
Authors: Das Sandip , Frye Chet , Muzykov Peter G. , Mandal Krishna C.
Published: April 2012

Cu2ZnSnS4 (CZTS) thin films have been prepared on Mo coated soda-lime glass (SLG) substrates using a low-cost spray pyrolysis technique. Aqueous solutions of CuCl, ZnCl2, SnCl4 and thiourea were used as precursors. Spray deposition was carried out at substrate temperatures of 300-400C with varying precursor concentrations. Structural, morphological and compositional characterization of as-deposited and annealed CZTS films were carried out by x-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX) and x-ray photoelectron spectroscopy (XPS). Optical and electrical properties were measured by UV-Vis spectroscopy, van der Pauw, and Hall-effect measurements. Heterojunction solar cells have been fabricated by deposition of n-CdS window layer on spray deposited p-CZTS films. Details of film fabrication, processing and characterization are presented. Our results show that CZTS-based solar cells can be designed and fabricated by a low-cost spraying technique for roll-to-roll commercial production.
Influence of Cathodic Potential on Structural and Optical Properties of ZnO;Mg Thin Film
Authors: Ishizaki Hiroki , Ito Seishiro
Published: April 2012

ZnO:Mg thin films were prepared on conductive substrates at cathodic potential of -0.8V and -0.975V from a magnesium nitrate aqueous solution containing zinc sulfite kept at 323K by electrochemical deposition techniques. These ZnO:Mg films had wurtzite structure, regardless of cathodic potential. With a decrease in cathodic potential, Mg/(Zn+Mg) atomic ratio of these thin films and optical band gap energy decreased. In particular, ZnO:Mg thin films obtained at cathodic potential of -0.9V had Mg/(Zn+Mg) atomic ratio of 0.077 and optical band gap energy of 3.79eV. Thus, optical properties and Mg/(Zn+Mg) atomic ratio of ZnO:Mg thin films were controlled by cathodic potential.
The Effect of Thermal Annealing on the Properties of IGZO TFT Prepared by Atmospheric Pressure Plasma Jet
Authors: Wu Chien-Hung , Chang Kow-Ming , Huang Sung-Hung , Deng I-Chung , Wu Chin-Jyi , Chiang Wei-Han , Lin Je-Wei , Chang Chia-Chiang
Published: April 2012

We fabricated bottom gate TFTs with IGZO channel layer deposited by atmospheric pressure plasma jet (APPJ). The effect of thermal annealing on the properties of IGZO TFTs was studied. After post annealing, the IGZO thin films showed a smooth and dense structure. The transistors annealed at 300oC showed clear switching behavior with a negative threshold voltage of -0.571 V and a mobility of 2.6 cm2/V-s. After 500oC post annealing, IGZO thin film showed an amorphous-like phase and the average transmittance is more than 80% in the visible range. Good electrical characteristics were achieved, including a threshold voltage of 6.74V, a subthreshold swing of 1.54 V/dec, a mobility of 10.31 cm2/V-s and a large Ion/Ioff ratio of 3.28x108.
Step-Roughened N-face GaN Surface on InGaN Light-Emitting Diodes Using a Laser Decomposition Process
Authors: Lin Chia-Feng , Chen Sih-Han , Hsieh Tsung-Han , Huang Wan-Chun , Yu Tzu-Yun , Tsai Peng-Han
Published: April 2012

InGaN-based light-emitting diodes (LEDs) with a step-inverted pyramidal structure at the GaN/patterned-sapphire interface were fabricated through laser decomposition and wet crystallographic etching processes. By partially reducing the GaN/patterned-sapphire contact area through the step-inverted pyramidal structure, the light output power of the treated LED structure was enhanced 21% compared to a conventional LED structure. By increasing the pulse operation current to 200mA (176 A/cm2), the related efficiency droop and the peak wavelength blueshift phenomenon of the electroluminescence spectrum were almost the same in both LED structures. The light emission intensity at the laser-treated stripe-line region, with the roughened N-face GaN surface, was higher than at the truncated triangle-shaped patterned-sapphire region. LEDs with step-inverted pyramidal structures and GaN/air-gap/patterned-sapphire structures increased light-extraction efficiency for high efficiency nitride-based LEDs.
Electrocatalysis in Polymer Electrolyte Fuel Cells: From Fundamentals to Applications
Authors: Schmidt Thomas J.
Published: April 2012

The goal of this work is to summarize the most important developments in electrocatalysis for polymer electrolyte fuel cells (PEFCs). The focus is on fundamental studies to gain insight into reaction mechanisms, correlations of surface atom composition and arrangements with reactivity towards the oxygen reduction reaction (ORR). Additionally, these findings will be complemented with important requirements for durability for and in devices. Both activity and durability challenges will be discussed in the light of the technical targets for low temperature fuel cells for both automotive and stationary applications.
Recent Advances in Non-Precious Metal Electrocatalysts for Oxygen Reduction in PEM Fuel Cells
Authors: Lefèvre Michel , Dodelet Jean-Pol
Published: April 2012

Polymer electrolyte membrane fuel cells (PEMFC) are electrical power generators for a wide range of possible applications, but are still considered too expensive for many. To reduce their cost, much research has focused on replacing the expensive Pt-based electrocatalysts in PEMFCs with a lower-cost alternative. Fe-based cathode catalysts are a promising alternative. To compete with Pt-based cathode catalysts, non-precious metal catalysts must meet three key criteria: have high catalytic activity, allow for high power density at meaningful cell voltages and have adequate operational stability/durability. Over the last three years our research group at INRS-EMT has made significant progress in achieving these criteria including a cathode catalyst with a power density of 0.75W cm−2 at 0.6V under H2/O2, a meaningful voltage for PEMFC operation, comparable with that of a commercial Pt-based cathode tested under identical conditions.
Effect of Ligand, Support and Solvent on the O2 Binding of Nonprecious Metal Catalysts: An Ab Initio Study
Authors: Zhu Hongjuan , Paddison Stephen J. , Zawodzinski Thomas A.
Published: April 2012

Non-precious metal (NPM) catalysts have been under extensive studyto replace expensive platinum based catalysts utilized in the Oxygen Reduction Reaction (ORR) in polymer electrolyte membrane (PEM) fuel cells. In this work, density functional theory (DFT) calculations were undertakento understand the effect of structure, choice of the central metal, and support on a series of ML2 catalysts where M = Cu(I), Cu(II), Fe(II), Fe(III), Ni(II), and Co(II), and L = diaminetriazole (M-N2). O2 binding was determinedto involve the d-based anti-bonding dxz and dz2 orbitals of thecatalysts and two singly occupied π* orbitals of O2. When the catalysts were considered in an aqueous media (i.e., unsupported), Fe(II) exhibited the strongest O2 binding,followed by Co(II), Fe(III), Ni(II) and Cu(I); whereas the binding was observed in Cu(II).This order in the binding seems to correlate with the energy gap between the d orbitals of the metal cation and the π* of the triplet O2, with the smaller the gap resulting in stronger O2 binding. When a support and an explicit solvent moleculewere considered, the catalysts showed comparable O2 and H2O bindingmaking the O2 binding through H2O displacement much less favorable. Hence, the difference in the binding of H2O and O2 is seen to be critical in evaluating the activity of the catalyst.
Prompting Effect of Fe on the Kinetics and Electrocatalytic Activity of CoPc/C for Oxygen Reduction Reaction
Authors: Ding Lei , Qiao Jinli , Dai Xiangfeng , Zhang Jing , Tian Binglun , Liu Shiyao
Published: April 2012

Effects of Fe addition on the electrocatalytic activity for oxygen reduction reaction (ORR) are studied over carbon-supported CoPc, which were prepared using a milling method combined with a heat-treatment procedure. The catalysts were characterized using CV, LSV and RDE in acid electrolyte. The results reveal that CoPc/C modified with 5%Fe after 600oC shows the best activity when Fe loading ranged from 0.5% to 8% nominal, and was higher than that of pure CoPc/C catalyst at the same measuring conditions. The ORR mechanism on the CoPc5%Fe/C-600 catalyst is mainly between 2e- and 3e- reduction pathway which is better than a 2e- reduction pathway on pure CoPc/C catalyst. The degree of oxygen reduction is improved on CoPc/C catalyst after modification with Fe.
Bridge to Fuel Cell Molecular Catalysis: 3D Non-Platinum Group Metal Catalyst in MEAs
Authors: Zhu Xiaobing , Kerr John B. , He Qinggang , Hwang Gisuk , Martin Zulima , Clark Kyle , Weber Adam Z. , Zhao Nana
Published: April 2012

Transition metal porphyrin complexes have been mounted in a three dimensional homogenous distribution inside the ionomer of catalyst layers in MEAs to achieve competitive fuel cell catalysis activity. The effect of electrode components including ionomer, carbon, catalyst, and mediator, and ionomer film thickness, is investigated in fuel cell molecular catalysis system. Membrane electrode assembly (MEA) durability testing has been conducted. SEM and TEM techniques are employed to investigate molecular catalysis electrode micro- and nano- structure and morphology. To date, surprisingly, the best fuel cell performance, i.e. 1280 mA/cm2 of maximum/short-circuit current density is achieved, approaching that of Pt-based electrode, indicating higher turnover frequencies than Pt although with poorer voltages.
Chronic coexistence of two troponin T isoforms in adult transgenic mouse cardiomyocytes decreased contractile kinetics and caused dilatative remodeling
Authors: Yu Zhi-Bin , Wei Hongguang , Jin J.-P.
Published: April 2012

Our previous in vivo and ex vivo studies suggested that coexistence of two or more troponin T (TnT) isoforms in adult cardiac muscle decreased cardiac function and efficiency (Huang QQ, Feng HZ, Liu J, Du J, Stull LB, Moravec CS, Huang X, Jin JP, Am J Physiol Cell Physiol 294: C213–C22, 2008; Feng HZ, Jin JP, Am J Physiol Heart Circ Physiol 299: H97–H105, 2010). Here we characterized Ca2+-regulated contractility of isolated adult cardiomyocytes from transgenic mice coexpressing a fast skeletal muscle TnT together with the endogenous cardiac TnT. Without the influence of extracellular matrix, coexistence of the two TnT isoforms resulted in lower shortening amplitude, slower shortening and relengthening velocities, and longer relengthening time. The level of resting cytosolic Ca2+ was unchanged, but the peak Ca2+ transient was lowered and the durations of Ca2+ rising and decaying were longer in the transgenic mouse cardiomyocytes vs. the wild-type controls. Isoproterenol treatment diminished the differences in shortening amplitude and shortening and relengthening velocities, whereas the prolonged durations of relengthening and Ca2+ transient in the transgenic cardiomyocytes remained. At rigor state, a result from depletion of Ca2+, resting sarcomere length of the transgenic cardiomyocytes became shorter than that in wild-type cells. Inhibition of myosin motor diminished this effect of TnT function on cross bridges. The length but not width of transgenic cardiomyocytes was significantly increased compared with the wild-type controls, corresponding to longitudinal addition of sarcomeres and dilatative remodeling at the cellular level. These dominantly negative effects of normal fast TnT demonstrated that chronic coexistence of functionally distinct variants of TnT in adult cardiomyocytes reduces contractile performance with pathological consequences.
Hair cell BK channels interact with RACK1, and PKC increases its expression on the cell surface by indirect phosphorylation
Authors: Surguchev Alexei , Bai Jun-Ping , Joshi Powrnima , Navaratnam Dhasakumar
Published: April 2012

Large conductance (BK) calcium activated potassium channels (Slo) are ubiquitous and implicated in a number of human diseases including hypertension and epilepsy. BK channels consist of a pore forming α-subunit (Slo) and a number of accessory subunits. In hair cells of nonmammalian vertebrates these channels play a critical role in electrical resonance, a mechanism of frequency selectivity. Hair cell BK channel clusters on the surface and currents increase along the tonotopic axis and contribute significantly to the responsiveness of these hair cells to sounds of high frequency. In contrast, messenger RNA levels encoding the Slo gene show an opposite decrease in high frequency hair cells. To understand the molecular events underlying this paradox, we used a yeast two-hybrid screen to isolate binding partners of Slo. We identified Rack1 as a Slo binding partner and demonstrate that PKC activation increases Slo surface expression. We also establish that increased Slo recycling of endocytosed Slo is at least partially responsible for the increased surface expression of Slo. Moreover, analysis of several PKC phosphorylation site mutants confirms that the effects of PKC on Slo surface expression are likely indirect. Finally, we show that Slo clusters on the surface of hair cells are also increased by increased PKC activity and may contribute to the increasing amounts of channel clusters on the surface of high-frequency hair cells.
Reciprocal regulation controlling the expression of CPI-17, a specific inhibitor protein for the myosin light chain phosphatase in vascular smooth muscle cells
Authors: Kim Jee In , Urban Mark , Young Garbo D. , Eto Masumi
Published: April 2012

Cellular activity of the myosin light chain phosphatase (MLCP) determines agonist-induced force development of smooth muscle (SM). CPI-17 is an endogenous inhibitor protein for MLCP, responsible for mediating G-protein signaling into SM contraction. Fluctuations in CPI-17 expression occur in response to pathological stresses, altering excitation-contraction coupling in SM. Here, we determined the signaling pathways regulating CPI-17 expression in rat aorta tissues and the cell culture using a pharmacological approach. CPI-17 transcription was suppressed in response to the proliferative stimulus with platelet-derived growth factor (PDGF) through the ERK1/2 pathway, whereas it was elevated in response to inflammatory, stress-induced and excitatory stimuli with tranforming growth factor-β, IL-1β, TNFα, sorbitol, and serotonin. CPI-17 transcription was repressed by inhibition of JNK, p38, PKC, and Rho-kinase (ROCK). The mouse and human CPI-17 gene promoters were governed by the proximal GC-boxes at the 5′-flanking region, where Sp1/Sp3 transcription factors bound. Sp1 binding to the region was more prominent in intact aorta tissues, compared with the SM cell culture, where the CPI-17 gene is repressed. The 173-bp proximal promoter activity was negatively and positively regulated through PDGF-induced ERK1/2 and sorbitol-induced p38/JNK pathways, respectively. By contrast, PKC and ROCK inhibitors failed to repress the 173-bp promoter activity, suggesting distal enhancer elements. CPI-17 transcription was insensitive to knockdown of myocardin/Kruppel-like factor 4 small interfering RNA or histone deacetylase inhibition. The reciprocal regulation of Sp1/Sp3-driven CPI-17 expression through multiple kinases may be responsible for the adaptation of MLCP signal and SM tone to environmental changes.
Impaired long-range synchronization of gamma oscillations in the neocortex of a mouse lacking Kv3.2 potassium channels
Authors: Harvey Michael , Lau David , Civillico Eugene , Rudy Bernardo , Contreras Diego
Published: April 2012

Inhibitory interneurons play a critical role in the generation of gamma (20–50 Hz) oscillations, either by forming mutually inhibitory networks or as part of recurrent networks with pyramidal cells. A key property of fast spiking interneurons is their ability to generate brief spikes and high-frequency spike trains with little accommodation. However, the role of their firing properties in network oscillations has not been tested in vivo. Studies in hippocampus in vitro have shown that high-frequency spike doublets in interneurons play a key role in the long-range synchronization of gamma oscillations with little phase lag despite long axonal conduction delays. We generated a knockout (KO) mouse lacking Kv3.2 potassium channel subunits, where infragranular inhibitory interneurons lose the ability both to sustain high-frequency firing and reliably generate high-frequency spike doublets. We recorded cortical local field potentials in anesthetized and awake, restrained mice. Spontaneous activity of the KO and the wild-type (WT) showed similar content of gamma and slow (0.1–15 Hz) frequencies, but the KO showed a significantly larger decay of synchronization of gamma oscillations with distance. Coronal cuts in the cortex of WT mice decreased synchronization to values similar to the intact KO. The synchronization of the slow oscillation showed little decay with distance in both mice and was largely reduced after coronal cuts. Our results show that the firing properties of inhibitory interneurons are critical for long-range synchronization of gamma oscillations, and emphasize that intrinsic electrophysiological properties of single cells may play a key role in the spatiotemporal characteristics of network activity.
Low error discrimination using a correlated population code
Authors: Schwartz Greg , Macke Jakob , Amodei Dario , Tang Hanlin , Berry Michael J.
Published: April 2012

We explored the manner in which spatial information is encoded by retinal ganglion cell populations. We flashed a set of 36 shape stimuli onto the tiger salamander retina and used different decoding algorithms to read out information from a population of 162 ganglion cells. We compared the discrimination performance of linear decoders, which ignore correlation induced by common stimulation, with nonlinear decoders, which can accurately model these correlations. Similar to previous studies, decoders that ignored correlation suffered only a modest drop in discrimination performance for groups of up to ∼30 cells. However, for more realistic groups of 100+ cells, we found order-of-magnitude differences in the error rate. We also compared decoders that used only the presence of a single spike from each cell with more complex decoders that included information from multiple spike counts and multiple time bins. More complex decoders substantially outperformed simpler decoders, showing the importance of spike timing information. Particularly effective was the first spike latency representation, which allowed zero discrimination errors for the majority of shape stimuli. Furthermore, the performance of nonlinear decoders showed even greater enhancement compared with linear decoders for these complex representations. Finally, decoders that approximated the correlation structure in the population by matching all pairwise correlations with a maximum entropy model fit to all 162 neurons were quite successful, especially for the spike latency representation. Together, these results suggest a picture in which linear decoders allow a coarse categorization of shape stimuli, whereas nonlinear decoders, which take advantage of both correlation and spike timing, are needed to achieve high-fidelity discrimination.
Prefrontal cortical mechanisms underlying delayed alternation in mice
Authors: Rossi Mark A. , Hayrapetyan Volodya Y. , Maimon Benjamin , Mak Krystal , Je H. Shawn , Yin Henry H.
Published: April 2012

The prefrontal cortex (PFC) has been implicated in the maintenance of task-relevant information during goal-directed behavior. Using a combination of lesions, local inactivation, and optogenetics, we investigated the functional role of the medial prefrontal cortex (mPFC) in mice with a novel operant delayed alternation task. Task difficulty was manipulated by changing the duration of the delay between two sequential actions. In experiment 1, we showed that excitotoxic lesions of the mPFC impaired acquisition of delayed alternation with long delays (16 s), whereas lesions of the dorsal hippocampus and ventral striatum, areas connected with the PFC, did not produce any deficits. Lesions of dorsal hippocampus, however, significantly impaired reversal learning when the rule was changed from alternation to repetition. In experiment 2, we showed that local infusions of muscimol (an agonist of the GABAA receptor) into mPFC impaired performance even when the animal was well trained, suggesting that the mPFC is critical not only for acquisition but also for successful performance. In experiment 3, to examine the mechanisms underlying the role of GABAergic inhibition, we used Cre-inducible Channelrhodopsin-2 to activate parvalbumin (PV)-expressing GABAergic interneurons in the mPFC of PV-Cre transgenic mice as they performed the task. Using whole cell patch-clamp recording, we demonstrated that activation of PV-expressing interneurons in vitro with blue light in brain slices reliably produced spiking and inhibited nearby pyramidal projection neurons. With similar stimulation parameters, in vivo stimulation significantly impaired delayed alternation performance. Together these results demonstrate a critical role for the mPFC in the acquisition and performance of the delayed alternation task.
A Unified Framework for Detecting Rare Variant Quantitative Trait Associations in Pedigree and Unrelated Individuals via Sequence Data
Authors: Liu Dajiang J. , Leal Suzanne M.
Published: April 2012

Objectives: There is great interest to sequence unrelated or pedigree samples for detecting rare variant quantitative trait associations. In order to reduce the cost of sequencing and improve power, many studies sequence selected samples with extreme traits. Existing methods for detecting rare variant associations were developed for unrelated samples. Methods are needed to analyze (selected or randomly ascertained) pedigree samples. Methods: We propose a unified framework of modeling extreme trait genetic associations (MEGA) with rare variants. Using MEGA and appropriate permutation algorithms, many rare variant tests can be extended to family data. As an application, we compared study designs using both sib-pairs and unrelated individuals. Extensive simulations were carried out using realistic population genetic and complex trait models. Results: It is demonstrated that when extreme sampling is implemented within equal-sized cohorts of unrelated individuals or sib-pairs, analyzing unrelated individuals is consistently more powerful than studying sib-pairs. A higher portion of rare variants can be identified through sequencing unrelated samples compared to sibs. Alternatively, if samples are ascertained using fixed thresholds from an infinite-sized population, sequencing one sib with the most extreme trait from each extreme concordant sib-pair is consistently the most powerful design. Conclusions: MEGA will play an important role in the analysis of sequence-based genetic association studies.
Trends in Outcome and Hospitalization Charges of Adult Patients Admitted with Botulism in the United States
Authors: Souayah Nizar , Shafiq Mehyar Lubna , Khan Hafiz M.R. , Yacoub Hussam A. , Abed Al-Kariem A Al-Qudah Zaid , Nasar Abu , Begum Sheikh Zubeda , Maybodi Leila , Qureshi Adnan I.
Published: April 2012

Background: To assess the impact of new therapeutic strategies on outcomes and hospitalization charges among adult patients with botulism in the United States. Methods: We determined in-hospital outcomes and charges for patients with botulism hospitalized in 1993–1994 and compared them with those observed among patients hospitalized in 2006–2007. Mortality, length of stay, and hospitalization charges were calculated. Age, sex, race, ethnicity, and discharge status were also reported. Results: There were 66 and 132 admissions of adult patients with botulism in 1993–1994 and 2006–2007, respectively. Men predominance was observed in 2006–2007 compared to women predominance during the 1993–1994 time period. There was no significant difference in the average length of stay and in-hospital mortality rate between the two groups studied. However, in the 2006–2007 group, there was a significant increase in the mean hospitalization charges (USD 126,092 ± 120,535 vs. USD 83,623 ± 82,084; p = 0.0107) and in the proportion of patients requiring mechanical ventilation when compared to 1993–1994 (34 vs. 13.6%; p < 0.0001). Conclusion: Botulism continues to be an infrequent cause of hospitalization, with a significant increase in the average hospitalization charges in 2006–2007 when compared to 1993–1994, despite a nonsignificant change in the mortality rate and average length of hospitalization.
A Critical Evaluation of the Preventive Effect of Antiviral Therapy on the Development of Hepatocellular Carcinoma in Patients with Chronic Hepatitis C or B: A Novel Approach by Using Meta-Regression
Authors: Shen Ying-Chun , Hsu Chiun , Cheng Chia-Chi , Hu Fu-Chang , Cheng Ann-Lii
Published: April 2012

Background: The extent of the effect of antiviral therapy and its predictors in preventing hepatocellular carcinoma (HCC) development in patients with chronic hepatitis C (CHC) or B (CHB) remain unclear. Methods: We conducted a systemic review and meta-analysis of published randomized controlled trials (RCTs) and cohort studies (CSs) up to December 2010. Preventive efficacy was measured as absolute reduction in 3- and 5-year cumulative incidence of HCC with antiviral therapy. Predictors for efficacy were identified by using meta-regression. Results: Twenty-two studies (5 RCTs; 17 CSs) were included for analysis. Antiviral therapy reduced 5-year cumulative incidence of HCC by 7.8% (95% CI 4.6–11.1; p < 0.0001) in patients with CHC and by 7.1% (95% CI 4.1–10.2; p < 0.0001) in patients with CHB. The efficacy was significant as early as 3 years after antiviral therapy. While adjusting for available study-level, patient and virological factors, RCT and higher sustained virological response were identified as pertinent predictors of superior preventive efficacy in patients with CHC, whereas lower hepatitis B virus e antigen seropositivity was identified in patients with CHB. Antiviral therapy did not result in differential preventive efficacy between cirrhotic and noncirrhotic patients with CHC or CHB. Conclusion: Antiviral therapy can reduce 3- and 5-year cumulative incidence of HCC in patients with CHC or CHB.
Fibrinolytic status in acute coronary syndromes: Evidence of differences in relation to clinical features and pathophysiological pathways
Authors: Shantsila Eduard , Montoro-Garcia Silvia , Tapp Luke , Apostolakis Stavros , Wrigley Benjamin , Lip Gregory
Published: April 2012

Limited data are available on the role of innate fibrinolysis in acute coronary syndromes (ACS). In the present study we evaluated the dynamic alterations of fibrinolytic markers in patients presenting with ACS. Tissue-type-(tPA) and urokinase type-(uPA) plasminogen activators, plasminogen activator inhibitor (PAI-1) antigen and activity and thrombin activatable fibrinolysis inhibitor (TAFI) were analysed in 50 patients with ST elevation myocardial infarction (STEMI), 47 non-STEMI patients (NSTEMI), 40 patients with stable coronary artery disease (CAD) and 39 controls. The parameters were measured on day 1 and days 3, 7 and 30. Counts of monocyte subsets, monocyte-platelet aggregates and plasma inflammatory cytokines were assessed on admission. On day 1, TAFI was higher in NSTEMI vs. STEMI (p<0.001) while PAI-1 activity was higher in STEMI (p<0.001). In STEMI, uPA activity levels was low on day 1 but significantly increased on day 30 (p<0.001). TAFI levels were increased in NSTEMI on day 1 and gradually reduced by day 30 (p<0.05). In STEMI, TAFI levels peaked at day 7 (p<0.05) and dropped significantly by day 30 (p<0.05). CD14++CD16+ monocytes were independently associated with PAI-1 activity in ACS (p=0.03). Monocyte-platelet aggregates rather than platelet-free monocytes were an independent determinant of tPA, PAI-1 antigen and TAFI on a multivariate analysis (p<0.05). There are significant differences in fibrinolytic activity between patients with STEMI and NSTEMI. These changes could reflect the role of these factors in post-MI myocardial healing. Monocyteplatelet interactions are independently associated with the regulation of the fibrinolytic status in ACS.

Note: The editorial process for this article was fully handled by Prof. Christian Weber, Editor-in-Chief.
Local β-Adrenergic Stimulation Overcomes Source-Sink Mismatch to Generate Focal Arrhythmia
Authors: Myles Rachel C. , Wang Lianguo , Kang Chaoyi , Bers Donald M. , Ripplinger Crystal M.
Published: April 2012

Rationale:

β-Adrenergic receptor stimulation produces sarcoplasmic reticulum Ca
2+
overload and delayed afterdepolarizations in isolated ventricular myocytes. How delayed afterdepolarizations are synchronized to overcome the source-sink mismatch and produce focal arrhythmia in the intact heart remains unknown.

Objective:

To determine whether local β-adrenergic receptor stimulation produces spatiotemporal synchronization of delayed afterdepolarizations and to examine the effects of tissue geometry and cell-cell coupling on the induction of focal arrhythmia.

Methods and Results:

Simultaneous optical mapping of transmembrane potential and Ca
2+
transients was performed in normal rabbit hearts during subepicardial injections (50 μL) of norepinephrine (NE) or control (normal Tyrode's solution). Local NE produced premature ventricular complexes (PVCs) from the injection site that were dose-dependent (low-dose [30–60 μmol/L], 0.45±0.62 PVCs per injection; high-dose [125–250 μmol/L], 1.33±1.46 PVCs per injection;
P
<0.0001) and were inhibited by propranolol. NE-induced PVCs exhibited abnormal voltage–Ca
2+
delay at the initiation site and were inhibited by either sarcoplasmic/endoplasmic reticulum Ca
2+
-ATPase inhibition or reduced perfusate [Ca
2+
], which indicates a Ca
2+
-mediated mechanism. NE-induced PVCs were more common at right ventricular than at left ventricular sites (1.48±1.50 versus 0.55±0.89,
P
<0.01), and this was unchanged after chemical ablation of endocardial Purkinje fibers, which suggests that source-sink interactions may contribute to the greater propensity to right ventricular PVCs. Partial gap junction uncoupling with carbenoxolone (25 μmol/L) increased focal activity (2.18±1.43 versus 1.33±1.46 PVCs per injection,
P
<0.05), which further supports source-sink balance as a critical mediator of Ca
2+
-induced PVCs.

Conclusions:

These data provide the first experimental demonstration that localized β-adrenergic receptor stimulation produces spatiotemporal synchronization of sarcoplasmic reticulum Ca
2+
overload and release in the intact heart and highlight the critical nature of source-sink balance in initiating focal arrhythmias.
Role of RhoB in the Regulation of Pulmonary Endothelial and Smooth Muscle Cell Responses to Hypoxia
Authors: Wojciak-Stothard Beata , Zhao Lan , Oliver Eduardo , Dubois Olivier , Wu Yixing , Kardassis Dimitris , Vasilaki Eleftheria , Huang Minzhou , Mitchell Jane A. , Harrington Louise S. , Prendergast George C. , Wilkins Martin R.
Published: April 2012

Rationale:

RhoA and Rho kinase contribute to pulmonary vasoconstriction and vascular remodeling in pulmonary hypertension. RhoB, a protein homologous to RhoA and activated by hypoxia, regulates neoplastic growth and vasoconstriction but its role in the regulation of pulmonary vascular function is not known.

Objective:

To determine the role of RhoB in pulmonary endothelial and smooth muscle cell responses to hypoxia and in pulmonary vascular remodeling in chronic hypoxia-induced pulmonary hypertension.

Methods and Results:

Hypoxia increased expression and activity of RhoB in human pulmonary artery endothelial and smooth muscle cells, coincidental with activation of RhoA. Hypoxia or adenoviral overexpression of constitutively activated RhoB increased actomyosin contractility, induced endothelial permeability, and promoted cell growth; dominant negative RhoB or manumycin, a farnesyltransferase inhibitor that targets the vascular function of RhoB, inhibited the effects of hypoxia. Coordinated activation of RhoA and RhoB maximized the hypoxia-induced stress fiber formation caused by RhoB/mammalian homolog of Drosophila diaphanous-induced actin polymerization and RhoA/Rho kinase-induced phosphorylation of myosin light chain on Ser19. Notably, RhoB was specifically required for hypoxia-induced factor-1α stabilization and for hypoxia- and platelet-derived growth factor-induced cell proliferation and migration. RhoB deficiency in mice markedly attenuated development of chronic hypoxia-induced pulmonary hypertension, despite compensatory expression of RhoA in the lung.

Conclusions:

RhoB mediates adaptational changes to acute hypoxia in the vasculature, but its continual activation by chronic hypoxia can accentuate vascular remodeling to promote development of pulmonary hypertension. RhoB is a potential target for novel approaches (eg, farnesyltransferase inhibitors) aimed at regulating pulmonary vascular tone and structure.