bluuebunny/crossref_metadata_2025 huggingface dataset:
Surface Modification of Nitinol by Biocompatible Passive Films
Authors: Katić Jozefina , Metikoš-Huković Mirjana
Published: October 2010

Nitinol, near-equiatomic nickel-titanium alloy, exhibits unique properties, shape memory effect and superelasticity, and is therefore of a huge importance in biochemical engineering for medical devices. The high corrosion resistivity and biocompatibility are required in application of Nitinol as implant material for cardiovascular stents and orthodontic wires. Thus, a main goal of this work was designing and optimizing corrosion resistant and biocompatible coatings on Nitinol. Electrochemical methods were used for the functionalization of the Nitinol surface with anodically formed oxide films in acetic acid and investigation of their barrier and semiconducting properties.
Seedless Copper Electrochemical Deposition on PVD Resistive Substrates as a Replacement/Enhancement for PVD Cu Seed Layers in HAR TSVs
Authors: Armini Silvia , Wilson Chris J. , Moussa Alain , Franquet Alexis , Vanstreels Kris , Atanasova Tanya , Radisic Alex , Civale Yann , Van Ammel Annemie , El-Mekki Zaid , Bryce George , Ruythooren Wouter
Published: October 2010

The results of a wet alkaline seed deposition process directly on barrier layers or thin adhesion promoter films, such as CVD Co are presented. This solution has been successfully used for copper plating on blanket and patterned Though Silicon Via (TSVs) wafers covered with either silicon oxide/PVD Ta(N)/CVD Co or silicon oxide/PVD Ti/CVD Co stacks. Such direct plated films were used as seed layers for subsequent copper plating from a conventional sulfuric acid electroplating bath. The effect of the plated stack composition and thicknesses, processing waveform and applied current on the plating rate and morphology of the deposited copper has been investigated.
Molecular Scale Growth of Electrolytic Copper Foils
Authors: Kondo Kazuo , Okamoto Naoki , Saito Takeyasu , Takeuchi Minoru
Published: October 2010

The electrolytic copper foils were found to grow with lateral growth of macro steps on the (100)Cu single copper crystal of the f.c.c. structure. The copper foils with geratin additive have the (111) orientation and have the triangular pyramidal morphology. With chloride only and geratin and chloride, the crystal have (110) orientation and pyramidal morphology. Both of these crystals grow with the lateral growth of macro steps on the (100) surfaces. Smooth electrolytic copper foil used for the Lithium-ion battery is formed with additives of chloride, MPS and DDAC. The crystal refinement occurs and about 0.1μmin diameter crystals form. The additives of chloride, MPS and DDAC increase their nucleation sites.
Dielectric Properties of Polymer Electrolyte Membranes Measured by Two-Port Transmission Line Technique
Authors: Lu Zijie , Lanagan Michael , Manias Evangelos , Macdonald Digby
Published: October 2010

The microwave dielectric properties of perfluorosulfonic acid membranes are characterized by a two-port transmission line technique. Two dielectric relaxation modes are observed in the microwave region (0.045-26 GHz) at 25{degree sign}C. The higher frequency process observed is identified as the cooperative relaxation of bulk-like water, whose amount was found to increase linearly with water content in the polymer. The lower-frequency process, characterized by longer relaxation times (20-70 picoseconds), is attributed to water molecules that are loosely bound to sulfonate groups. The loosely bound water amount was found to increase with hydration level at low water content, and levels-off at higher water contents. Flemion SH150, which has an equivalent weight of 909 g/equiv, displays higher dielectric strengths for both of these water modes compared to Nafion 117 (equivalent weight of 1100 g/equiv).
Diffusion-Controlled Growth Model for Electrodeposited Cobalt Nanowires in Highly Ordered Aluminum Oxide Membrane
Authors: Ghahremaninezhad Ahmad , Dolati Abolghasem
Published: October 2010

This work studies the electrochemical growth behavior of cobalt nanowires in highly ordered aluminum oxide membrane. Considering the electrodeposition of metallic nanowires, cation concentration profile in each nano pore was calculated. With assumption of linear diffusion zone on the growing surface of nanowires, a modified Cottrell equation was evaluated. To confirm the model, the Co nanowires were electrodeposited into porous anodic aluminum oxide (AAO) templates and the mechanism of deposition was studied. Comparing the results of model and the experiments has proved the accuracy of the model. Also, it was observed that the growth of the Co nanowires was controlled mainly by diffusion process. With these considerations, the diffusion coefficient of the Co2+ cation in pore was determined about D = 2.14×10-5 cm2.s-1. SEM and TEM analysis showed high density and uniform nanowires that retained the shape of pores.
Effects of Quantum Confinement on Interdependence between DOS Spectrum and C(V) Characteristic of Si Nanowire-Based MOS Structure
Authors: Ligatchev Valeri , Chin Sai Kong
Published: October 2010

Interrelation between capacitance - gate voltage [C(V)] characteristic and density-of-states (DOS) spectrum [N(E)] is analyzed using experimental C(V) data obtained from silicon-nanowire (SiNW) based metal-oxide-semiconductor (MOS) structure, solution of coupled Schrödinger-Poisson (SP) equations (with full treatment on quantum confinement) and semi-classical Fredholm integral equation (FIE) of the first kind. It is shown that FIE valid for NW-based MOS structures with NW radii a equal to or bigger than 10 nm at temperature T exceeding 38 K. However, significant deviations from FIE is predicted by SP treatment for a = 5 nm and T = 5 K. Such deviation is attributed to considerable effect of quantum confinement not only on N(E) distributions, but also on fundamental statistical distribution functions of electrons.
Influence of Surface Pretreatment of MWNTs Support on PEFC Performance
Authors: Mohanapriya Subramanian , Sridhar Parthasarathi , Pitchumani Sethuraman , Shukla Ashok
Published: October 2010

The influence of surface characteristics of multi-walled carbon nanotubes (MWNTs) support on the catalytic performance of PEFC electrodes is investigated by using oxidized and non-oxidized MWNTs as the supports for platinum. The defect-free morphology, high electrical conductivity and favorable pore-size distribution of non-oxidized MWNTs ameliorate catalytic activity and electrochemical stability of platinum. Physico-chemical properties of oxidized and non-oxidized MWNTs and the respective catalysts are studied by BET surface-area, XRD, XPS and TEM measurements. Electrochemical stability of MWNTs-supported platinum as PEFC electrodes is assessed using potential cycling and potentiostatic techniques. Owing to the higher corrosion-resistance, platinum on non-oxidized MWNTs show lower loss in electrochemical surface area (ESA) and also exhibit 22% lower corrosion current than oxidized MWNTs.
Effect of Different Surface Morphologies and Nitrogen Contents on the Electrochemical Activity of Nitrogen Doped Carbon Nanotubes towards Oxygen Reduction Reaction for Low Temperature Fuel Cells
Authors: Chen Zhu , Chen Zhongwei
Published: October 2010

Nitrogen doped carbon nanotubes (NCNTs) with different nitrogen content and surface morphology were synthesized by a chemical vapour deposition technique. The surface structure and nitrogen content of the NCNTs was controlled by the choice of growth catalyst and the relative nitrogen-carbon composition in the precursor solution. Based on the structural characterizations, NCNTs synthesized using ferrocene as growth catalyst exhibited large degree of surface defect and showed higher oxygen reduction reaction (ORR) activity compared with NCNTs synthesized using iron (II) phthalocyanine as growth catalyst. From the elemental composition analysis, the overall nitrogen content was also found to be positively correlated to the ORR activity of NCNTs catalysts. This report illustrates the viable methods in improving ORR activity of NCNT catalysts.
Gas (H2 and NO2) Sensor of ZnO Nanorods in Vacuum
Authors: Lim Hanna , Kim Jin-Tae , Jeong Soo-Hwan , Kang Sang-Woo , Yun Ju-Young , Shin Yong-Hyeon
Published: October 2010

Vertically-aligned resistive-type ZnO nanorod gas sensors have been successfully fabricated on alumina substrate with a patterned Pt-electrode by using sonochemical method. The responses are characterized by measuring resistance at 250 ° in the vacuum chamber where total pressure of 10 torr is maintained and various concentrations of dilute H2 or NO2 are injected. The gas sensors exhibit the responses of 7 % and 1650 % are respectively at 50 ppm of H2 and NO2, and increase as gas concentration rises to 1000 ppm. Compared with previous studies conducted at atmospheric pressure, the response to H2 gas measured at the vacuum is improved, while that to NO2 is similar, promising that ZnO nanorod gas sensors can be developed into high performance gas sensor for vacuum process.
Electrodeposition of Gold, Silver on Carbon Nanotube Thin Films
Authors: Lam Si-Ty , Scott Graeme , Zhou Zhang-Lin
Published: October 2010

In a carbon nanotube (CNT) thin film, CNTs form complicated networks with numerous junctions where individual CNTs intersect or simply contact other CNTs. This results in a significant reduction of the electrical conductivity of the film as compared with the intrinsic conductivity of the CNT. Because of this, the current state of the art CNT films are unsuitable for many information display applications. We were able to overcome this issue by developing an electrodeposition process in which a precise amount of metal such as gold or silver was deposited onto CNT films. This process uniquely allows a small amount of metal to be preferentially and uniformly deposited on the CNTs and at CNT junctions. With additional heat treatment, the conductivity of the CNT film increases by more than four times while its optical transmittance remains unchanged.
Pulsed Electric Fields for Fabrication of Copper/Carbon Nanotube and Carbon Nanotube Films
Authors: McCrabb Heather , Taylor E. J. , Inman Maria , Devlin Christie , Leines Matthew
Published: October 2010

To meet the demands of future interconnects on integrated circuits, a pulse/pulse reverse electrocodeposition process for depositing copper/carbon nanotube composites and a pulse/pulse reverse electrophoretic deposition process for depositing stand alone carbon nanotubes is being developed. Traditionally, electrocodeposition and electrophoretic deposition processes are achieved using direct current. The addition of the pulsed electric field provides an improved level of processing control through the optimization of the pulse parameters in conjunction with boundary layer and feature size considerations. This paper will discuss the results obtained to date and provide a path forward for the technology.
Two-Dimensional Hexagonally Ordered Mesoporous Carbon Synthesized Via a One-Step Method for Supercapacitors
Authors: Zhou Tianxiang , Jiang Fengping , Xia Nannan , Chen Jingxing , Yuan Dingsheng
Published: October 2010

A two-dimensional hexagonally ordered mesoporous carbon (OMC) has been synthesized directly from the carbonization of silica / triblock / butanol copolymers using F127 as structure-directing agents and butanol as the carbon precursors. The synthesized product has been characterized by means of different techniques including transmission electron microscopy, N2 adsorption-desorption, Fourier transform infrared spectroscopy. Electrochemical properties are tested by cyclic voltammetry, and the maximum specific capacitance is 170 F g-1 in 6.0 mol L-1KOH at the sweep rate of 1 mV s-1.
A Facile Method to Prepare Nanosheets Bismuth Trioxide for Electrochemical Capacitors
Authors: Xia Nannan , Zhou Tianxiang , Mo Shanshan , Zhou Shuangli , Zou Wujun , Yuan Dingsheng
Published: October 2010

In this article, a simple strategy for the synthesis of nanosheets clusters under room temperature is presented. Nanosheets Bi2O3 clusters were directly precipitated from the Bi(NO3)3 solution in the presence of surfactant (Hexadecyl trimethyl ammonium Bromide) under strong alkaline conditions. XRD and SEM were employed to characterize the Bi2O3 particles. The electrochemical properties of the prepared Bi2O3 materials were studied using cyclic voltammetry and galvanostatic charge / discharge in 6.0 mol L-1 KOH electrolyte. The electrochemical measurements revealed that the speciﬁc capacitance of nanosheets Bi2O3 clusters reached 996 F g-1 at current density of 100 mA g-1. The cyclic life of synthesized materials was also measured and the capacitance only declined 4.2 % after 1000 cycles.
Tungsten(VI) Oxide Flake-Wall Film Electrodes for Photoelectrochemical Oxygen Evolution from Water
Authors: Amano Fumiaki , Li Ding , Ohtani Bunsho
Published: October 2010

A vertically arrayed flake film, "flake-wall film", of monoclinic tungsten(VI) oxide (WO3) was prepared on a transparent conductive glass. The WO3 flake-wall film exhibited superior performance for photoelectrochemical water oxidation under visible-light irradiation compared to that of a film consisting of horizontally laminated WO3 flakes. The small difference between photocurrent densities under front-side irradiation and back-side irradiation indicates the excellent electron transport property of the flake-wall film.
p53 and TIGAR regulate cardiac myocyte energy homeostasis under hypoxic stress
Authors: Kimata Masaki , Matoba Satoaki , Iwai-Kanai Eri , Nakamura Hideo , Hoshino Atsushi , Nakaoka Mikihiko , Katamura Maki , Okawa Yoshifumi , Mita Yuichiro , Okigaki Mitsuhiko , Ikeda Koji , Tatsumi Tetsuya , Matsubara Hiroaki
Published: October 2010

Bioenergetic homeostasis is altered in heart failure and may play an important role in pathogenesis. p53 has been implicated in heart failure, and although its role in regulating tumorigenesis is well characterized, its activities on cellular metabolism are just beginning to be understood. We investigated the role of p53 and its transcriptional target gene TP53-induced glycolysis and apoptosis regulator ( TIGAR) in myocardial energy metabolism under conditions simulating ischemia that can lead to heart failure. Expression of p53 and TIGAR was markedly upregulated after myocardial infarction, and apoptotic myocytes were decreased by 42% in p53-deficient mouse hearts compared with those in wild-type mice. To examine the effect of p53 on energy metabolism, cardiac myocytes were exposed to hypoxia. Hypoxia induced p53 and TIGAR expression in a p53-dependent manner. Knockdown of p53 or TIGAR increased glycolysis with elevated fructose-2,6-bisphosphate levels and reduced myocyte apoptosis. Hypoxic stress decreased phosphocreatine content and the mitochondrial membrane potential of myocytes without changes in ATP content, the effects of which were prevented by the knockdown of TIGAR. Inhibition of glycolysis by 2-deoxyglucose blocked these bioenergetic effects and TIGAR siRNA-mediated prevention of apoptosis, and, in contrast, overexpression of TIGAR reduced glucose utilization and increased apoptosis. Our data demonstrate that p53 and TIGAR inhibit glycolysis in hypoxic myocytes and that inhibition of glycolysis is closely involved in apoptosis, suggesting that p53 and TIGAR are significant mediators of cellular energy homeostasis and cell death under ischemic stress.
Heterogeneity in MT1-MMP activity with ischemia-reperfusion and previous myocardial infarction: relation to regional myocardial function
Authors: Dixon Jennifer A. , Gaillard William F. , Rivers William T. , Koval Christine N. , Stroud Robert E. , Mukherjee Rupak , Spinale Francis G.
Published: October 2010

After a myocardial infarction (MI), an episode of ischemia-reperfusion (I/R) can result in a greater impairment of left ventricular (LV) regional function (LVRF) than that caused by an initial I/R episode in the absence of MI. Membrane type-I matrix metalloproteinase (MT1-MMP) proteolytically processes the myocardial matrix and is upregulated in LV failure. This study tested the central hypothesis that a differential induction of MT1-MMP occurs and is related to LVRF after I/R in the context of a previous MI. Pigs with a previous MI [3 wk postligation of the left circumflex artery (LCx)] or no MI were randomized to undergo I/R [60-min/120-min left anterior descending coronary artery (LAD) occlusion] or no I/R as follows: no MI and no I/R ( n = 6), no MI and I/R ( n = 8), MI and no I/R ( n = 8), and MI and I/R ( n = 8). Baseline LVRF (regional stroke work, sonomicrometry) was lower in the LAD region in the MI group compared with no MI (103 ± 12 vs. 188 ± 26 mmHg·mm, P < 0.05) and remained lower with peak ischemia (35 ± 8 vs. 88 ± 17 mmHg·mm, P < 0.05). Using a novel interstitial microdialysis method, MT1-MMP was directly measured and was over threefold higher in the LCx region and over twofold higher in the LAD region in the MI group compared with the no MI group at baseline. MT1-MMP fluorogenic activity was persistently elevated in the LCx region in the MI and I/R group but remained unchanged in the LAD region. In contrast, no changes in MT1-MMP occurred in the LCx region in the no MI and I/R group but increased in the LAD region. MT1-MMP mRNA was increased by over threefold in the MI region in the MI and I/R group. In conclusion, these findings demonstrate that a heterogeneous response in MT1-MMP activity likely contributes to regional dysfunction with I/R and that a subsequent episode of I/R activates a proteolytic cascade within the MI region that may contribute to a continued adverse remodeling process.
The mitochondrial bioenergetic phenotype for protection from cardiac ischemia in SUR2 mutant mice
Authors: Aggarwal Nitin T. , Pravdic Danijel , McNally Elizabeth M. , Bosnjak Zeljko J. , Shi Nian-Qing , Makielski Jonathan C.
Published: October 2010

The sulfonylurea receptor-2 (SUR2) is a subunit of ATP-sensitive potassium channels (KATP) in heart. Mice with the SUR2 gene disrupted (SUR2m) are constitutively protected from ischemia-reperfusion (I/R) cardiac injury. This was surprising because KATP, either sarcolemmal or mitochondrial or both, are thought to be important for cardioprotection. We hypothesized that SUR2m mice have an altered mitochondrial phenotype that protects against I/R. Mitochondrial membrane potential (ΔΨm), tolerance to Ca2+ load, and reactive oxygen species (ROS) generation were studied by fluorescence-based assays, and volumetric changes in response to K+ were measured by light scattering in isolated mitochondria. For resting SUR2m mitochondria compared with wild type, the ΔΨm was less polarized (46.1 ± 0.4 vs. 51.9 ± 0.6%), tolerance to Ca2+ loading was increased (163 ± 2 vs. 116 ± 2 μM), and ROS generation was enhanced with complex I [8.5 ± 1.2 vs. 4.9 ± 0.2 arbitrary fluorescence units (afu)/s] or complex II (351 ± 51.3 vs. 166 ± 36.2 afu/s) substrates. SUR2m mitochondria had greater swelling in K+ medium (30.2 ± 3.1%) compared with wild type (14.5 ± 0.6%), indicating greater K+ influx. Additionally, ΔΨm decreased and swelling increased in the absence of ATP in SUR2m, but the sensitivity to ATP was less compared with wild type. When the mitochondria were subjected to hypoxia-reoxygenation, the decrease in respiration rates and respiratory control index was less in SUR2m. ΔΨm maintenance in the SUR2m intact myocytes was also more tolerant to metabolic inhibition. In conclusion, the cardioprotection observed in the SUR2m mice is associated with a protected mitochondrial phenotype resulting from enhanced K+ conductance that partially dissipated ΔΨm. These results have implications for possible SUR2 participation in mitochondrial KATP.
Cardiac-specific overexpression of dominant-negative CREB leads to increased mortality and mitochondrial dysfunction in female mice
Authors: Watson Peter A. , Birdsey Nicholas , Huggins Gordon S. , Svensson Eric , Heppe Daniel , Knaub Leslie
Published: October 2010

Cardiac failure is associated with diminished activation of the transcription factor cyclic nucleotide regulatory element binding-protein (CREB), and heart-specific expression of a phosphorylation-deficient CREB mutant in transgenic mice [dominant negative CREB (dnCREB) mice] recapitulates the contractile phenotypes of cardiac failure (Fentzke RC, Korcarz CE, Lang RM, Lin H, Leiden JM. Dilated cardiomyopathy in transgenic mice expressing a dominant-negative CREB transcription factor in the heart. J Clin Invest 101: 2415–2426, 1998). In the present study, we demonstrated significantly elevated mortality and contractile dysfunction in female compared with male dnCREB mice. Female dnCREB mice demonstrated a 21-wk survival of only 17% compared with 67% in males ( P < 0.05) and exclusively manifest decreased cardiac peroxisome proliferator-activated receptor-γ coactivator-1α and estrogen-related receptor-α content, suggesting sex-related effects on cardiac mitochondrial function. Hearts from 4-wk-old dnCREB mice of both sexes demonstrated diminished mitochondrial respiratory capacity compared with nontransgenic controls. However, by 12 wk of age, there was a significant decrease in mitochondrial density (citrate synthase activity) and deterioration of mitochondrial structure, as demonstrated by transmission electron microscopy, in female dnCREB mice, which were not found in male transgenic littermates. Subsarcolemmal mitochondria isolated from hearts of female, but not male, dnCREB mice demonstrated increased ROS accompanied by decreases in the expression/activity of the mitochondrial antioxidants MnSOD and glutathione peroxidase. These results demonstrate that heart-specific dnCREB expression results in mitochondrial respiratory dysfunction in both sexes; however, increased oxidant burden, reduced antioxidant expression, and disrupted mitochondrial structure are exacerbated by the female sex, preceding and contributing to the greater contractile morbidity and mortality. These results provide further support for the role of the CREB transcription factor in regulating mitochondrial integrity and identify a critical pathway that may contribute to sex differences in heart failure.
Differential effects of adenosine A2aand A2breceptors on cardiac contractility
Authors: Chandrasekera P. Charukeshi , McIntosh Victoria J. , Cao Frank X. , Lasley Robert D.
Published: October 2010

The mammalian myocardium expresses four adenosine receptor (AR) subtypes: A1AR, A2aAR, A2bAR, and A3AR. The A1AR is well known for its profound antiadrenergic effects, but the roles of other AR subtypes in modulating contractility remain inconclusive. Thus, the objective of this study was to determine the direct and indirect effects of A2aAR and A2bAR on cardiac contractility. Experiments were conducted in paced, constant pressure-perfused isolated hearts from wild-type (WT), A2aAR knockout (KO), and A2bAR KO mice. The A2aAR agonist CGS-21680 did not alter basal contractility or β-adrenergic receptor agonist isoproterenol (Iso)-mediated positive inotropic responses, and Iso-induced effects were unaltered in A2aAR KO hearts. However, A2aAR gene ablation resulted in a potentiation of the antiadrenergic effects mediated by the A1AR agonist 2-chloro- N-cyclopentyladenosine. The nonselective AR agonist 5′- N-ethylcarboxamido adenosine and the selective A2bAR agonist BAY 60-6583 induced coronary flow-independent increases in contractility, but BAY 60-6583 did not alter Iso-induced contractile responses. The A1AR antiadrenergic effect was not potentiated in A2bAR KO hearts. The expression of all four AR subtypes in the heart and ventricular myocytes was confirmed using real-time quantitative PCR. Taken together, these results indicate that A2aAR does not increase cardiac contractility directly but indirectly alters contractility by modulating the A1AR antiadrenergic effect, whereas A2bAR exerts direct contractile effects but does not alter β-adrenergic or A1AR antiadrenergic effects. These results indicate that multiple ARs differentially modulate cardiac function.
Short-term magnesium deficiency upregulates sphingomyelin synthase and p53 in cardiovascular tissues and cells: relevance to the de novo synthesis of ceramide
Authors: Altura Burton M. , Shah Nilank C. , Li Zhiqiang , Jiang Xian-Cheng , Zhang Aimin , Li Wenyan , Zheng Tao , Perez-Albela Jose Luis , Altura Bella T.
Published: October 2010

The present study tested the hypotheses that 1) short-term dietary deficiency of magnesium (21 days) in rats would result in the upregulation of sphingomyelin synthase (SMS) and p53 in cardiac and vascular (aortic) smooth muscles, 2) low levels of Mg2+added to drinking water would either prevent or greatly reduce the upregulation of both SMS and p53, 3) exposure of primary cultured vascular smooth muscle cells (VSMCs) to low extracellular Mg2+concentration ([Mg2]o) would lead to the de novo synthesis of ceramide, 4) inhibition of either SMS or p53 in primary culture VSMCs exposed to low [Mg2+]owould lead to reductions in the levels of de novo ceramide synthesis, and 5) inhibition of sphingomyelin palmitoyl-CoA transferase (SPT) or ceramide synthase (CS) in primary cultured VSMCs exposed to low [Mg2+]owould lead to a reduction in the levels of de novo ceramide synthesis. The data indicated that short-term magnesium deficiency (10% normal dietary intake) resulted in the upregulation of SMS and p53 in both ventricular and aortic smooth muscles; even very low levels of water-borne Mg2+(e.g., 15 mg·l−1·day−1) either prevented or ameliorated the upregulation in SMS and p53. Our experiments also showed that VSMCs exposed to low [Mg2+]oresulted in the de novo synthesis of ceramide; the lower the [Mg2+]o, the greater the synthesis of ceramide. In addition, the data indicated that inhibition of either SMS, p53, SPT, or CS in VSMCs exposed to low [Mg2+]oresulted in marked reductions in the de novo synthesis of ceramide.
Exercise improves the dilatation function of mesenteric arteries in postmyocardial infarction rats via a PI3K/Akt/eNOS pathway-mediated mechanism
Authors: Wang Youhua , Wang Shengpeng , Wier W. Gil , Zhang Quanjiang , Jiang Hongke , Li Qiuxia , Chen Shengfeng , Tian Zhenjun , Li Youyou , Yu Xiaojiang , Zhao Ming , Liu Jinjun , Yang Jing , Zhang Jing , Zang Weijin
Published: October 2010

Myocardial infarction (MI) has been shown to induce endothelial dysfunction in peripheral resistance arteries and thus increase peripheral resistance. This study was designed to investigate the underlying mechanisms of post-MI-related dysfunctional dilatation of peripheral resistance arteries and, furthermore, to examine whether exercise may restore dysfunctional dilatation of peripheral resistance arteries. Adult male Sprague-Dawley rats were divided into three groups: sham-operated, MI, and MI + exercise. Ultrastructure and relaxation function of the mesenteric arteries, as well as phosphatidylinositol-3 kinase (PI3K), Akt kinases (Akt), endothelial nitric oxide synthase (eNOS) activity, and phosphorylation of PI3K, Akt, and eNOS by ACh were determined. Post-MI rats exhibited pronounced ultrastructural changes in mesenteric artery endothelial cells and endothelial dysfunction. In addition, the activities of PI3K, Akt, and eNOS, and their phosphorylation by ACh were significantly attenuated in mesenteric arteries ( P < 0.05–0.01). After 8 wk of exercise, not only did endothelial cells appeared more normal in structure, but also ameliorated post-MI-associated mesenteric arterial dysfunction, which were accompanied by elevated activities of PI3K, Akt, and eNOS, and their phosphorylation by ACh ( P < 0.05–0.01). Importantly, inhibition of either PI3K or eNOS attenuated exercise-induced restoration of the dilatation function and blocked PI3K, Akt, and eNOS phosphorylation by ACh in the mesenteric arteries. These data demonstrate that MI induces dysfunctional dilation of peripheral resistance arteries by degradation of endothelial structural integrity and attenuating PI3K-Akt-eNOS signaling. Exercise may restore dilatation function of peripheral resistance arteries by protecting endothelial structural integrity and increasing PI3K-Akt-eNOS signaling cascades.
Regulation of endogenous ENaC functional expression by CFTR and ΔF508-CFTR in airway epithelial cells
Authors: Rubenstein Ronald C. , Lockwood Shannon R. , Lide Ellen , Bauer Rebecca , Suaud Laurence , Grumbach Yael
Published: October 2010

The functional expression of the epithelial sodium channel (ENaC) appears elevated in cystic fibrosis (CF) airway epithelia, but the mechanism by which this occurs is not clear. We tested the hypothesis that the cystic fibrosis transmembrane conductance regulator (CFTR) alters the trafficking of endogenously expressed human ENaC in the CFBE41o−model of CF bronchial epithelia. Functional expression of ENaC, as defined by amiloride-inhibited short-circuit current ( Isc) in Ussing chambers, was absent under control conditions but present in CFBE41o−parental and ΔF508-CFTR-overexpressing cells after treatment with 1 μM dexamethasone (Dex) for 24 h. The effect of Dex was mimicked by incubation with the glucocorticoid hydrocortisone but not with the mineralocorticoid aldosterone. Application of trypsin to the apical surface to activate uncleaved, “near-silent” ENaC caused an additional increase in amiloride-sensitive Iscin the Dex-treated cells and was without effect in the control cells, suggesting that Dex increased ENaC cell surface expression. In contrast, Dex treatment did not stimulate amiloride-sensitive Iscin CFBE41o−cells that stably express wild-type (wt) CFTR. CFBE41o−wt cells also had reduced expression of α- and γ-ENaC compared with parental and ΔF508-CFTR-overexpressing cells. Furthermore, application of trypsin to the apical surface of Dex-treated CFBE41o−wt cells did not stimulate amiloride-sensitive Isc, suggesting that ENaC remained absent from the surface of these cells even after Dex treatment. We also tested the effect of trafficking-corrected ΔF508-CFTR on ENaC functional expression. Incubation with 1 mM 4-phenylbutyrate synergistically increased Dex-induced ENaC functional expression in ΔF508-CFTR-overexpressing cells. These data support the hypothesis that wt CFTR can regulate the whole cell, functional, and surface expression of endogenous ENaC in airway epithelial cells and that absence of this regulation may foster ENaC hyperactivity in CF airway epithelia.
Inflammation in fetal sheep from intra-amniotic injection of Ureaplasma parvum
Authors: Collins Jennifer J. P. , Kallapur Suhas G. , Knox Christine L. , Nitsos Ilias , Polglase Graeme R. , Pillow J. Jane , Kuypers Elke , Newnham John P. , Jobe Alan H. , Kramer Boris W.
Published: October 2010

Bronchopulmonary dysplasia is associated with chorioamnionitis and fetal lung inflammation. Ureaplasma species are the bacteria most frequently isolated from chorioamnionitis. Very chronic ureaplasma colonization of amniotic fluid causes low-grade lung inflammation and functional lung maturation in fetal sheep. Less is known about shorter exposures of the fetal lung. Therefore, we hypothesized that ureaplasmas would cause an acute inflammatory response that would alter lung development. Singleton ovine fetuses received intra-amniotic Ureaplasma parvum serovar 3 or control media at 110, 117, or 121 days and were delivered at 124 days gestational age (term = 150 days). Inflammation was assessed by 1) cell counts in bronchoalveolar lavage fluid (BALF), and 2) cytokine mRNA measurements, immunohistochemistry, and flow cytometry for inflammatory cells and elastin and α-smooth muscle actin (α-SMA) staining in lung tissue. Neutrophils were increased in BALF 3 days after exposure to ureaplasmas ( P = 0.01). Myeloperoxidase-positive cells increased after 3 days ( P = 0.03), and major histocompatibility complex (MHC) class II-positive cells increased after 14 days of ureaplasma exposure ( P = 0.001). PU.1 (macrophage marker)- or CD3 (T lymphocyte marker)-positive cells were not induced by ureaplasmas. CD3-positive cells in the posterior mediastinal lymph node increased in ureaplasma-exposed animals at 3, 7, and 14 days ( P = 0.002). Focal elastin depositions decreased in alveolar septa at 14 days ( P = 0.002), whereas α-SMA increased in arteries and bronchioli. U. parvum induced a mild acute inflammatory response and changed elastin and α-SMA deposition in the lung, which may affect lung structure and subsequent development.
Adiponectin-deficient mice are protected against tobacco-induced inflammation and increased emphysema
Authors: Miller Marina , Pham Alexa , Cho Jae Youn , Rosenthal Peter , Broide David H.
Published: October 2010

Adiponectin is a cytokine with both proinflammatory and anti-inflammatory properties that is expressed in epithelial cells in the airway in chronic obstructive pulmonary disease-emphysema (COPD-E). To determine whether adiponectin modulates levels of lung inflammation in tobacco smoke-induced COPD-E, we used a mouse model of COPD-E in which either adiponectin-deficient or wild-type (WT) mice were exposed to tobacco smoke for 6 mo. Outcomes associated with tobacco smoke-induced COPD-E were quantitated including lung inflammation [bronchoalveolar lavage (BAL) and total and differential cell count], lung mediators of inflammation (cytokines and chemokines), air space enlargement (i.e., linear intercept), and lung function (tissue elastance) in the different groups of mice. Whereas exposure of WT mice to tobacco smoke for 6 mo induced significant lung inflammation (increased total BAL cells, neutrophils, and macrophages), adiponectin-deficient mice had minimal BAL inflammation when exposed to tobacco smoke for 6 mo. In addition, whereas chronic tobacco-exposed WT mice had significantly increased levels of lung mediators of inflammation [i.e., TNF-α, keratinocyte-derived chemokine (KC), and adiponectin] as well as significantly increased air space enlargement (increased linear intercept) and decreased tissue elastance, exposure of adiponectin-deficient mice to chronic tobacco smoke resulted in no further increase in lung mediators, air space enlargement, or tissue elastance. In vitro studies demonstrated that BAL macrophages derived from adiponectin-deficient mice incubated in media containing tobacco smoke expressed minimal TNF-α or KC compared with BAL macrophages from WT mice. These studies suggest that adiponectin plays an important proinflammatory role in tobacco smoke-induced COPD-E.
Nielsen Type Numbers of Self-Maps on the Real Projective Plane
Authors: Wang Jiaoyun
Published: October 2010

Employing the induced endomorphism of the fundamental group and using the homotopy classification of self-maps of real projective plane "Equation missing", we compute completely two Nielsen type numbers, "Equation missing"(f) and "Equation missing"(f), which estimate the number of periodic points of f and the number of fixed points of the iterates of map f.
Retreatment of Patients Nonresponsive to Pegylated Interferon and Ribavirin with Daily High-Dose Consensus Interferon
Authors: Meyer Douglas F. , Tobias Hillel , Min Albert D. , Rajendra Arathi , Zic Ivanka , Brettholz Edward , Clain David J. , Klion Franklin , Bernstein David , Bodenheimer Henry C.
Published: October 2010

Background. Current treatment of chronic hepatitis C with pegylated interferon and ribavirin has the ability to eliminate viral infection in about half of the patients treated. Therapeutic options, for those with remaining chronic hepatitis, will remain limited until
novel antivirals become available in the future. Consensus interferon is currently available and has demonstrated clinical efficacy with superior invitro antiviral activity, but the maximum tolerated dose is not defined. Methods. We assessed the efficacy of daily high-dose (24 ug) consensus interferon with weight-based (1000–1200 mg daily) ribavirin in HCV genotype 1-infected non-responder patients. Results. Six adverse events were documented in five patients, and the trial was terminated with no subject achieving viral clearance. Conclusions. The occurrence of serious adverse events effectively defined the upper limit of acceptable dose, while also revealing that this dose did not offer enhanced sustained viral clearance.
Composite Algorithms for Minimization over the Solutions of Equilibrium Problems and Fixed Point Problems
Authors: Yao Yonghong , Liou Yeong-Cheng
Published: October 2010

The purpose of this paper is to solve the minimization problem of finding x∗ such that x∗ = argminx∈Γ∥x∥2, where Γ stands for the intersection set of the solution set of the equilibrium problem and the fixed points set of a nonexpansive mapping. We first present two new composite algorithms (one implicit and one explicit). Further, we prove that the proposed composite algorithms converge strongly to x∗.
Use of Preputial Skin as Cutaneous Graft after Nevus Excision
Authors: D'Alessio A. , Piro E. , Brugnoni M. , Abati L.
Published: October 2010

We report a four-year-old boy with a nevus covering all the plantar side of his second finger on the left foot. He was also affected by congenital phimosis. Surgical excision of the nevus was indicated, but the skin defect would have been too large to be directly closed. The foreskin was taken as a full-thickness skin graft to cover the cutaneous defect of the finger. The graft intake was favourable and provided a functional repair with good aesthetic characteristic.
Hodgkin's Lymphoma: A Review of Neurologic Complications
Authors: Grimm Sean , Chamberlain Marc
Published: October 2010

Hodgkin's lymphoma is a hematolymphoid neoplasm, primarily of B cell lineage, that has unique histologic, immunophenotypic, and clinical features. Neurologic complications of Hodgkin's Lymphoma can be separated into those that result directly from the disease, indirectly from the disease, or from its treatment. Direct neurologic dysfunction from Hodgkin's Lymphoma results from metastatic intracranial spinal disease, epidural metastases causing spinal cord/cauda equina compression, leptomeningeal metastases, or intradural intramedullary spinal cord metastases. Indirect neurologic dysfunction may be caused by paraneoplastic disorders (such as paraneoplastic cerebellar degeneration or limbic encephalitis) and primary angiitis of the central nervous system. Hodgkin's lymphoma treatment typically includes chemotherapy or radiotherapy with potential treatment-related complications affecting the nervous system. Neurologic complications resulting from mantle-field radiotherapy include the “dropped head syndrome,” acute brachial plexopathy, and transient ischemic attacks/cerebral infarcts. Chemotherapy for Hodgkin's lymphoma may cause cerebral infarction (due to emboli from anthracycline-induced cardiomyopathy) and peripheral neuropathy.
Current Concepts in the Treatment of Retinitis Pigmentosa
Authors: Musarella Maria A. , MacDonald Ian M.
Published: October 2010

Inherited retinal degenerations, including retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA), affect 1 in 4000 individuals in the general population. A majority of the genes which are mutated in these conditions are expressed in either photoreceptors or the retinal pigment epithelium (RPE). There is considerable variation in the clinical severity of these conditions; the most severe being autosomal recessive LCA, a heterogeneous retinal degenerative disease and the commonest cause of congenital blindness in children. Here, we discuss all the potential treatments that are now available for retinal degeneration. A number of therapeutic avenues are being explored based on our knowledge of the pathophysiology of retinal degeneration derived from research on animal models, including: gene therapy, antiapoptosis agents, neurotrophic factors, and dietary supplementation. Technological advances in retinal implant devices continue to provide the promise of vision for patients with end-stage disease.
MGMT-Independent Temozolomide Resistance in Pediatric Glioblastoma Cells Associated with a PI3-Kinase–Mediated HOX/Stem Cell Gene Signature
Authors: Gaspar Nathalie , Marshall Lynley , Perryman Lara , Bax Dorine A. , Little Suzanne E. , Viana-Pereira Marta , Sharp Swee Y. , Vassal Gilles , Pearson Andrew D.J. , Reis Rui M. , Hargrave Darren , Workman Paul , Jones Chris
Published: October 2010

Sensitivity to temozolomide is restricted to a subset of glioblastoma patients, with the major determinant of resistance being a lack of promoter methylation of the gene encoding the repair protein DNA methyltransferase MGMT, although other mechanisms are thought to be active. There are, however, limited preclinical data in model systems derived from pediatric glioma patients. We screened a series of cell lines for temozolomide efficacy in vitro, and investigated the differential mechanisms of resistance involved. In the majority of cell lines, a lack of MGMT promoter methylation and subsequent protein overexpression were linked to temozolomide resistance. An exception was the pediatric glioblastoma line KNS42. Expression profiling data revealed a coordinated upregulation of HOX gene expression in resistant lines, especially KNS42, which was reversed by phosphoinositide 3-kinase pathway inhibition. High levels of HOXA9/HOXA10 gene expression were associated with a shorter survival in pediatric high-grade glioma patient samples. Combination treatment in vitro of pathway inhibition and temozolomide resulted in a highly synergistic interaction in KNS42 cells. The resistance gene signature further included contiguous genes within the 12q13-q14 amplicon, including the Akt enhancer PIKE, significantly overexpressed in the KNS42 line. These cells were also highly enriched for CD133 and other stem cell markers. We have thus shown an in vitro link between phosphoinositide 3-kinase–mediated HOXA9/HOXA10 expression, and a drug-resistant, progenitor cell phenotype in MGMT-independent pediatric glioblastoma. Cancer Res; 70(22); 9243–52. ©2010 AACR.
Therapeutic Targeting of TLR9 Inhibits Cell Growth and Induces Apoptosis in Neuroblastoma
Authors: Brignole Chiara , Marimpietri Danilo , Paolo Daniela Di , Perri Patrizia , Morandi Fabio , Pastorino Fabio , Zorzoli Alessia , Pagnan Gabriella , Loi Monica , Caffa Irene , Erminio Giovanni , Haupt Riccardo , Gambini Claudio , Pistoia Vito , Ponzoni Mirco
Published: October 2010

The Toll-like receptor 9 (TLR9) evolved to cope with pathogens, but it is expressed in a variety of tumors for reasons that are unclear. In this study, we report that neuroblastoma (NB) cells express functional TLR9. Liposome-complexed CpG oligonucleotides inhibited the proliferation of TLR9-expressing NB cells and induced caspase-dependent apoptotic cell death. Inhibitory oligonucleotides (iODNs) abrogated these effects. RNA interference reduced TLR9 expression but not to the level where functional responses to CpG were abolished. Compared with free CpG, liposomal formulations of NB-targeted CpG (TL-CpG) significantly prolonged the survival of mice bearing NB tumor xenografts. While CpG alone lacked antitumor efficacy in NOD/SCID/IL2rg−/− mice, TL-CpG retained significant efficacy related to direct effects on tumor cells. TLR9 expression in primary human NB specimens was found to correlate inversely with disease stage. Our findings establish functional expression of TLR9 in NB and suggest that TLR9 may represent a novel theranostic target in this disease. Cancer Res; 70(23); 9816–26. ©2010 AACR.
Deficiencies in the Fanconi Anemia DNA Damage Response Pathway Increase Sensitivity to HPV-Associated Head and Neck Cancer
Authors: Park Jung Wook , Pitot Henry C. , Strati Katerina , Spardy Nicole , Duensing Stefan , Grompe Markus , Lambert Paul F.
Published: October 2010

Patients with the rare genetic disease, Fanconi anemia (FA), are highly susceptible to squamous cell carcinomas arising at multiple anatomic sites including the head and neck region. Human papillomaviruses (HPVs), particularly HPV16, are associated with ∼20% of head and neck squamous cell carcinomas (HNSCCs) in the general population. Some but not other investigators have reported that HNSCCs in FA patients are much more frequently positive for HPV. In addition, studies have demonstrated an interaction between the HPV16 E7 oncoprotein and the FA pathway, a DNA damage response pathway deficient in FA patients. On the basis of these studies, it was hypothesized that the FA pathway contributes to repair of DNA damage induced by HPV16 E7, providing one explanation for why FA patients are predisposed to HPV-associated HNSCCs. To determine the importance of the FA pathway in modulating the oncogenic abilities of E7, we crossed K14E7 transgenic (K14E7) and fancD2 knockout mice (FancD2−/−) to establish K14E7/FancD2−/− and K14E7/FancD2+/+ mice and monitored their susceptibility to HNSCC when treated with a chemical carcinogen. K14E7/FancD2−/− mice had a significantly higher incidence of HNSCC compared with K14E7/FancD2+/+ mice. This difference correlated with an increased proliferative index and the increase in expression of biomarkers that are used to assess levels of DNA damage. These animal studies support the hypotheses that FA patients have increased susceptibility to HPV-associated cancer and that the FA DNA damage response pathway normally attenuates the oncogenic potential of HPV16 E7. Cancer Res; 70(23); 9959–68. ©2010 AACR.
Degradation of MDM2 by the Interaction between Berberine and DAXX Leads to Potent Apoptosis in MDM2-Overexpressing Cancer Cells
Authors: Zhang Xiaoling , Gu Lubing , Li Jiansha , Shah Noopur , He Jing , Yang Lin , Hu Qun , Zhou Muxiang
Published: October 2010

Berberine, a natural product derived from a plant used in Chinese herbal medicine, is reported to exhibit anticancer effects; however, its mechanism of action is not clearly defined. Herein, we demonstrate that berberine induces apoptosis in acute lymphoblastic leukemia (ALL) cells by downregulating the MDM2 oncoprotein. The proapoptotic effects of berberine were closely associated with both the MDM2 expression levels and p53 status of a set of ALL cell lines. The most potent apoptosis was induced by berberine in ALL cells with both MDM2 overexpression and a wild-type (wt)-p53, whereas no proapoptotic effect was detected in ALL cells that were negative for MDM2 and wt-p53. In contrast to the conventional chemotherapeutic drug doxorubicin, which induces p53 activation and a subsequent upregulation of MDM2, berberine strongly induced persistent downregulation of MDM2 followed by a steady-state activation of p53. We discovered that downregulation of MDM2 in ALL cells by berberine occurred at a posttranslational level through modulation of death domain-associated protein (DAXX), which disrupted the MDM2–DAXX–HAUSP interactions and thereby promoted MDM2 self-ubiquitination and degradation. Given that MDM2-overexpressing cancer cells are commonly chemoresistant, our findings suggest that this naturally derived agent may have a highly useful role in the treatment of cancer patients with refractory disease. Cancer Res; 70(23); 9895–904. ©2010 AACR.