bluuebunny/crossref_metadata_2025 huggingface dataset:
COORBIT SPACE THEORY FOR THE TOEPLITZ SHEARLET TRANSFORM
Authors: DAHLKE STEPHAN , HÄUSER SÖREN , TESCHKE GERD
Published: February 2012

In this paper we are concerned with the continuous shearlet transform in arbitrary space dimensions where the shear operation is of Toeplitz type. In particular, we focus on the construction of associated shearlet coorbit spaces and on atomic decompositions and Banach frames for these spaces.
WAVELET ANALYSIS OF PROTEIN MOTION
Authors: BENSON NOAH C. , DAGGETT VALERIE
Published: February 2012

As high-throughput molecular dynamics simulations of proteins become more common and the databases housing the results become larger and more prevalent, more sophisticated methods to quickly and accurately mine large numbers of trajectories for relevant information will have to be developed. One such method, which is only recently gaining popularity in molecular biology, is the continuous wavelet transform, which is especially well-suited for time course data such as molecular dynamics simulations. We describe techniques for the calculation and analysis of wavelet transforms of molecular dynamics trajectories in detail and present examples of how these techniques can be useful in data mining. We demonstrate that wavelets are sensitive to structural rearrangements in proteins and that they can be used to quickly detect physically relevant events. Finally, as an example of the use of this approach, we show how wavelet data mining has led to a novel hypothesis related to the mechanism of the protein γδ resolvase.
Wavelength Tuning by Temperature Control in MgO-Doped LiNbO3Waveguide Quasi-Phase-Matching Twin Photon Generation Device
Authors: Kakuno Shigenobu , Fujimura Masatoshi , Suhara Toshiaki
Published: February 2012

Waveguide quasi-phase-matching (QPM) twin photon generation (TPG) devices are the key device for future quantum communication. We examined the temperature dependences of the twin photon wavelengths of a MgO:LiNbO3waveguide Type-I QPM TPG device to clarify the possibility of twin photon wavelength tuning. It turned out that, in a typical device of 19 µm QPM grating period for TPG in the 1.55 µm band, twin photon wavelength tuning ranges of ≃16 and 300 nm can be obtained for degenerate and nondegenerate TPG, respectively, with temperature control in 25–150 °C.
Polarization Imaging Screen Using Vector Gratings Fabricated by Photocrosslinkable Polymer Liquid Crystals
Authors: Ono Hiroshi , Wada Takumi , Kawatsuki Nobuhiro
Published: February 2012

We demonstrate a polarization imaging screen using vector gratings by ultraviolet laser direct writing of polarized-light-induced optical anisotropy in photocrosslinkable polymer liquid crystals. For realizing a polarization-sensitive diffraction in the image screen, spatial distribution of the optical anisotropy has been designed, and the right- and left-hand side circularly polarized optical image are clearly reconstructed as the +1st- and -1st-ordered diffraction according to the theoretical expectation.
Ex-vivo Imaging of Thyroid Gland Using Ultrahigh-Resolution Optical Coherence Tomography at Wavelength from 800 to 1700 nm
Authors: Ishida Shutaro , Nishizawa Norihiko
Published: February 2012

Wavelength dependence of ex-vivo ultrahigh-resolution optical coherence tomography (UHR-OCT) imaging of thyroid gland using supercontinuum at wavelength from 800 to 1700 nm was demonstrated. The wavelength dependence of the thickness of follicular epithelium and fine structures such as round or oval follicles were observed from the UHR-OCT cross sectional images. The reconstructed en-face OCT images at all wavelength regions were obtained and the images of follicles with several different signal intensities were observed in 1060 and 1700 nm UHR-OCT images. To our knowledge, this is the first observation of wavelength dependence of OCT images of thyroid gland structure.
Convenient Fabrication of Fine Electrodes for Electric Measurement of Nanofibers by Nanoimprint Lithography
Authors: Iwai Hisanao , Yoshida Ken-ich , Heike Seiji , Hashizume Tomihiro , Shimomura Takeshi
Published: February 2012

We fabricated fine electrodes conventionally by nanoimprint lithography (NIL) to measure the electric properties of nanofibers and showed the performance of fine electrodes by the field-effect transistor (FET) measurement of a semiconducting polymer nanofiber. Furthermore, we performed the FET measurement of regioregular poly(3-hexylthiophene-2,5-diyl) (rr-P3HT) nanofibers using fabricated fine electrodes. As a result, the mobility was estimated to be 1.32×10-3 cm2 V-1 s-1, which was on the same order as that reported previously. The fabrication method was clarified to be effective for molecular electronics.
Characterization of In20Ge15Sb10Te55 Phase Change Material for Phase Change Memory with Low Power Operation and Good Data Retention
Authors: Morikawa Takahiro , Kurotsuchi Kenzo , Fujisaki Yoshihisa , Matsui Yuichi , Takaura Norikatsu
Published: February 2012

An indium-incorporated germanium–antimony–telluride material, In20Ge15Sb10Te55 (IGST), was investigated as a recording material for phase change memory. The crystallization temperature of IGST was 226 °C, which is 75 °C higher than that of conventional GST. The reset current of the device using IGST was about 10 mA for a plug 180 nm in diameter, which enabled a low-power operation, compared with the GST-based device. A cycle endurance of up to 1.5×104 was achieved. The data retention was estimated to be 10 years at 145 °C. These data clearly show that IGST exhibits promising characteristics as a recording material for phase change memory.
Normally-Off AlGaN/GaN Metal–Oxide–Semiconductor Heterostructure Field-Effect Transistor with Recessed Gate and p-GaN Back-Barrier
Authors: Kim Dong-Seok , Im Ki-Sik , Kang Hee-Sung , Kim Ki-Won , Bae Sung-Bum , Mun Jae-Kyoung , Nam Eun-Soo , Lee Jung-Hee
Published: February 2012

The recessed-gate AlGaN/GaN metal–oxide–semiconductor heterostructure field-effect transistors (MOSHFETs) with a p-GaN back-barrier studied in this work exhibited much lower buffer leakage current than those without the back-barrier. The threshold voltage of the device with the p-GaN back-barrier was controlled by varying the depth of gate recess etching, and a value as high as 2.9 V was obtained with deep gate-recess etching into the channel layer. The device structure has the advantage of both low leakage current and high threshold voltage, which is important for power-switching applications. In contrast, the performance parameters of the device, such as subthreshold slope and field-effect mobility, can be degraded owing to increased plasma damage with increasing recess depth.
Organic Photodiode with High Infrared Light Sensitivity Based on Tin Phthalocyanine/C60 Bulk Heterojunction and Optical Interference Effect
Authors: Ichikawa Musubu , Takeuchi Toshiki , Jeon Hyeon-Gu , Jin Yongwan , Lee Sangyoon , Kim Kyu-Sik
Published: February 2012

We demonstrated an organic near-infrared (NIR) photodiode on the basis of the bulk heterojunction (BHJ) structure by using tin phthalocyanine (SnPc) and C60 fullerene with a high incident photon–electron conversion efficiency (IPCE) of 50% at a wavelength of 750 nm. The cell showed optical responses to about 1000 nm and had a specific detectivity D
* of 1.59 ×1011 cm Hz1/2/W. The SnPc:C60 ratio in the BHJ layer influenced the optical response. Higher ratios enhanced NIR sensitivity but reduced the peak IPCE; the optimal ratio was 3:1. The optical interference of directly incident light and light reflected from an Al electrode was also examined to enhance the IPCE at longer wavelengths. With a 90-nm-thick C60 layer, the first antinode of the standing wave at a wavelength of 750 nm was located at the BHJ layer; this layer enhanced the IPCE at 700 and 800 nm but reduced it at 400 nm.
Drain Current Characteristics of Ferroelectric Gate-All-Around Si Nanowire Transistors Based on Drift/Diffusion Transport Theory
Authors: Ibata Masakazu , Ohmi Shun-ichiro , Ishiwara Hiroshi
Published: February 2012

The drain current vs gate voltage (I
D–V
G) and drain current vs drain voltage (I
D–V
D) characteristics of ferroelectric gate-all-around Si nanowire transistors are derived using the drift/diffusion transport theory. It is pointed out that the nonsaturated polarization in the ferroelectric film, which occurs near the drain region in the channel owing to the influence of the applied drain voltage, plays an important role in the calculation of the drain current as well as the polarization near the source region, and a graphical method using analytical expressions for the minor polarization hysteresis loops is presented to calculate the mobile charge density in the nanowire. By numerical analysis, the gate voltage range suitable for memory operation is determined in Si nanowire transistors with ferroelectric poly(vinylidene fluoride–trifluoroethylene) [P(VDF–TrFE)] gate films.
Near Infrared Single Photon Detector Using an InGaAs/InP Avalanche Photodiode Operated with a Bipolar Gating Signal
Authors: Bouzid Abdessattar , Park Jun-Bum , Kim Se Min , Moon Sung
Published: February 2012

We report a near infrared (NIR) single photon detector (SPD) using an InGaAs/InP avalanche photodiode (APD) operated with a bipolar rectangular gating signal. The use of the bipolar gating pulse enabled us to operate the APD well below the breakdown voltage during the gate-off time. As a result, it permits to decrease the lifetime of the trapped carriers, and then reduces the after-pulse noise of the detector. At a repetition rate of 200 MHz, the after-pulse probability is 8.2% less comparing to that of conventional gating signal SPD.
Development and Research on the Mechanism of Novel Mist Etching Method for Oxide Thin Films
Authors: Kawaharamura Toshiyuki , Hirao Takashi
Published: February 2012

A novel etching process with etchant mist was developed and applied to oxide thin films such as zinc oxide (ZnO), zinc magnesium oxide (ZnMgO), and indium tin oxide (ITO). By using this process, it was shown that precise control of the etching characteristics is possible with a reasonable etching rate, for example, in the range of 10–100 nm/min, and a fine pattern of high accuracy can also be realized, even though this is usually very difficult by conventional wet etching processes, for ZnO and ZnMgO. The mist etching process was found to be similarly and successfully applied to ITO. The mechanism of mist etching has been studied by examining the etching temperature dependence of pattern accuracy, and it was shown that the mechanism was different from that of conventional liquid-phase spray etching. It was ascertained that fine pattern etching was attained using mist droplets completely (or partly) gasified by the heat applied to the substrate. This technique was applied to the fabrication of a ZnO thin-film transistor (TFT) with a ZnO active channel length of 4 µm. The electrical properties of the TFT were found to be excellent with fine uniformity over the entire 4-in. wafer.
Average Voltage Measurements of Periodic Blocking Oscillation in Resistive Superconducting Quantum Interference Device Connected to Josephson Transmission Line
Authors: Mizugaki Yoshinao
Published: February 2012

Blocking oscillation (BO) is a unique operation mode of resistive superconducting quantum interference devices (RSQUIDs). The author presents experimental measurements of periodic BO by means of the average voltage method. Test circuits are fabricated using a Nb/AlO
x
/Nb integration process. The input/output voltage ratio in an RSQUID, of which the output is connected to a Josephson transmission line (JTL), becomes 2 under appropriate operation conditions. Since the voltage ratio is exactly proportional to the input/output switching frequency ratio, the results demonstrate the periodic BO, in which the numbers of switching during one period are 2 and 1 in the input and output junction, respectively.
BMP signaling in rats with TNBS-induced colitis following BMP7 therapy
Authors: Maric Ivana , Kucic Natalia , Turk Wensveen Tamara , Smoljan Ivana , Grahovac Blazenka , Zoricic Cvek Sanja , Celic Tanja , Bobinac Dragica , Vukicevic Slobodan
Published: February 2012

Beyond stimulating bone formation, bone morphogenetic proteins (BMPs) are important in development, inflammation, and malignancy of the gut. We have previously shown that BMP7 has a regenerative, anti-inflammatory, and antiproliferative effect on experimental inflammatory bowel disease (IBD) in rats. To further investigate the BMP signaling pathway we monitored the effect of BMP7 therapy on the BMP signaling components in the rat colon during different stages of experimentally induced colitis by 2,4,6-trinitrobenzene sulfonic acid (TNBS). The results showed a significantly decreased BMP7 expression in the acute phase, followed by a significantly increased BMP2 and decreased BMP6 expression during the chronic phase of colitis. BMP7 therapy influenced the expression of several BMPs with the most prominent effect on downregulation of BMP2 and upregulation of BMP4 in the chronic phase of colitis. Importantly, connective tissue growth factor and noggin expression were elevated in the acute stage and significantly decreased upon BMP7 therapy. BMP receptor I expression was unchanged, whereas BMP receptor II was decreased at day 2 and increased at days 14 and 30 of TNBS inflammation. However, an opposite pattern of expression following BMP7 therapy has been observed. BMP7 increased the expression of BR-Smad including Smad3 and Smad4. Inhibitory Smads were increased in colitis and significantly decreased following BMP7 therapy at later stages of the disease. We suggest that BMP signaling was altered during TNBS-induced colitis and was recovered with BMP7 administration, suggesting that IBD is a reversible process.
Src-mediated aryl hydrocarbon and epidermal growth factor receptor cross talk stimulates colon cancer cell proliferation
Authors: Xie Guofeng , Peng Zhongsheng , Raufman Jean-Pierre
Published: February 2012

The aryl hydrocarbon receptor (AhR) mediates many toxic effects of environmental pollutants. AhR also interacts with multiple growth factor-driven signaling pathways. In the course of examining effects of growth factors on proliferation of human colon cancer cells, we identified cross talk between AhR and the epidermal growth factor receptor (EGFR). In the present work, we explored underlying signal transduction mechanisms and functional consequences of this interaction. With the use of two human colon cancer cell lines, H508 and SNU-C4, we examined the effects of AhR ligands including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on cell proliferation and activation of EGFR, ERK1/2, and Src kinases. In colon cancer cells, 5-day incubation with TCDD stimulated a twofold dose-dependent increase in cell proliferation that was detectable with 1 nM and maximal with 30 nM TCDD. TCDD induced dose- and time-dependent phosphorylation of EGFR (Tyr845) and ERK1/2; maximal phosphorylation was observed 5 to 10 min after addition of 30 nM TCDD. Both TCDD-induced ERK1/2 phosphorylation and cell proliferation were abolished by AhR small interfering RNA, AhR-specific inhibitor CH223191, Src kinase inhibitor PP2, neutralizing antibodies against matrix metalloproteinase 7, heparin-binding-EGF-like growth factor and EGFR, EGFR inhibitors (AG1478 and PD168393), and MEK1 inhibitor PD98059. Coimmunoprecipitation experiments revealed that AhR forms a protein complex with Src and regulates Src activity by phosphorylating Src (Tyr416) and dephosphorylating Src (Tyr527). These data support novel observations that, in human colon cancer cells, Src-mediated cross talk between aryl hydrocarbon and EGFR results in ERK1/2 activation, thereby stimulating cell proliferation.
Regulation of phosphatase and tensin homolog on chromosome 10 in response to hypoxia
Authors: Qian Jinqiao , Ling Shukuan , Castillo Alexander C. , Long Bo , Birnbaum Yochai , Ye Yumei
Published: February 2012

Phosphatase and tensin homolog on chromosome 10 (PTEN) is downregulated during hypertrophic and cancerous cell growth, leading to activation of the prosurvival Akt pathway. However, PTEN regulation in cardiac myocytes upon exposure to hypoxia remains unclear. We explored the role of PTEN in response to hypoxia/ischemia in the myocardium. We validated that PTEN is a transcriptional target of activating transcription factor 2 (ATF-2) and is positively regulated via a p38/ATF-2 signaling pathway. Accordingly, hypoxia-induced upregulation of phosphorylation of ATF-2 and PTEN were reversed by a dominant negative mutant p38. Inhibition of PTEN in cardiomyocytes attenuated hypoxia-induced cell death and apoptosis. Cardiac-specific knockout of PTEN resulted in increased phosphorylation of Akt and forkhead box O 1 (forkhead transcription factors), limited infarct size in animals exposed to ischemia-reperfusion injury, and ameliorated deterioration of left ventricular function and remodeling following permanent coronary artery occlusion. In addition, the activation of Bim, FASL, and caspase was coupled with PTEN activation, all of which were attenuated by PTEN inhibition. In conclusion, cardiomyocyte-specific conditional PTEN deletion limited myocardial infarct size in an in vivo model of ischemia-reperfusion injury and attenuated adverse remodeling in a model of chronic permanent coronary artery ligation.
The rate of the deoxygenation reaction limits myoglobin- and hemoglobin-facilitated O2diffusion in cells
Authors: Endeward Volker
Published: February 2012

A mathematical model describing facilitation of O2diffusion by the diffusion of myoglobin and hemoglobin is presented. The equations are solved numerically by a finite-difference method for the conditions as they prevail in cardiac and skeletal muscle and in red cells without major simplifications. It is demonstrated that, in the range of intracellular diffusion distances, the degree of facilitation is limited by the rate of the chemical reaction between myglobin or hemoglobin and O2. The results are presented in the form of relationships between the degree of facilitation and the length of the diffusion path on the basis of the known kinetics of the oxygenation-deoxygenation reactions. It is concluded that the limitation by reaction kinetics reduces the maximally possible facilitated oxygen diffusion in cardiomyoctes by ∼50% and in skeletal muscle fibers by ∼ 20%. For human red blood cells, a reduction of facilitated O2diffusion by 36% is obtained in agreement with previous reports. This indicates that, especially in cardiomyocytes and red cells, chemical equilibrium between myoglobin or hemoglobin and O2is far from being established, an assumption that previously has often been made. Although the “O2transport function” of myoglobin in cardiac muscle cells thus is severely limited by the chemical reaction kinetics, and to a lesser extent also in skeletal muscle, it is noteworthy that the speed of release of O2from MbO2, the “storage function,” is not limited by the reaction kinetics under physiological conditions.
Trans-spinal direct current enhances corticospinal output and stimulation-evoked release of glutamate analog, D-2,3-3H-aspartic acid
Authors: Ahmed Zaghloul , Wieraszko Andrzej
Published: February 2012

Trans-spinal direct current (tsDC) stimulation is a modulator of spinal excitability and can influence cortically elicited muscle contraction in a polarity-dependent fashion. When combined with low-frequency repetitive cortical stimulation, cathodal tsDC [tsDC(−)] produces a long-term facilitation of cortically elicited muscle actions. We investigated the ability of this combined stimulation paradigm to facilitate cortically elicited muscle actions in spinal cord-injured and noninjured animals. The effect of tsDC—applied alone or in combination with repetitive spinal stimulation (rSS) on the release of the glutamate analog, D-2,3-3H-aspartate (D-Asp), from spinal cord preparations in vitro—was also tested. In noninjured animals, tsDC (−2 mA) reproducibly potentiated cortically elicited contractions of contralateral and ipsilateral muscles tested at various levels of baseline muscle contraction forces. Cortically elicited muscle responses in animals with contusive and hemisectioned spinal cord injuries (SCIs) were similarly potentiated. The combined paradigm of stimulation caused long-lasting potentiation of cortically elicited bilateral muscle contraction in injured and noninjured animals. Additional analysis suggests that at higher baseline forces, tsDC(−) application does not increase the rising slope of the muscle contraction but causes repeated firing of the same motor units. Both cathodal and anodal stimulations induced a significant increase of D-Asp release in vitro. The effect of the combined paradigm of stimulation (tsDC and rSS) on the concentration of extracellular D-Asp was polarity dependent. These results indicate that tsDC can powerfully modulate the responsiveness of spinal cord neurons. The results obtained from the in vitro preparation suggest that the changes in neuronal excitability were correlated with an increased concentration of extracellular glutamate. The combined paradigm of stimulation, used in our experiments, could be noninvasively applied to restore motor control in humans with SCI.
Hemodynamics and brain blood flow during posture change in younger women and postmenopausal women compared with age-matched men
Authors: Edgell H. , Robertson A. D. , Hughson R. L.
Published: February 2012

Increased incidence of orthostatic hypotension and presyncopal symptoms in young women could be related to hormonal factors that might be isolated by comparing cardiovascular and cerebrovascular responses to postural change in young and older men and women. Seven young women, 11 young men, 10 older women (>1 yr postmenopausal, no hormone therapy), and 9 older men participated in a supine-to-sit-to-stand test while measuring systemic hemodynamics, end-tidal Pco2, and blood flow velocity of the middle cerebral artery (MCA). Women had a greater reduction in stroke volume index compared with age-matched men (change from supine to standing: young women: −22.9 ± 1.6 ml/m2; young men: −14.4 ± 2.4 ml/m2; older women: −17.4 ± 3.3 ml/m2; older men: −13.8 ± 2.2 ml/m2). This was accompanied by offsetting changes in heart rate, particularly in young women, resulting in no age or sex differences in cardiac output index. Mean arterial pressure (MAP) was higher in older subjects and increased with movement to upright postures. Younger men and women had higher forearm vascular resistance that increased progressively in the upright posture compared with older men and women. There was no difference between sexes or ages in total peripheral resistance index. Women had higher MCA velocity, but both sexes had reduced MCA velocity while upright, which was a function of reduced blood pressure at the MCA and a significant reduction in end-tidal Pco2. The reductions in stroke volume index suggested impaired venous return in women, but augmented responses of heart rate and forearm vascular resistance protected MAP in younger women. Overall, these results showed significant sex and age-related differences, but compensatory mechanisms preserved MAP and MCA velocity in young women.
Effect of airway smooth muscle tone on airway distensibility measured by the forced oscillation technique in adults with asthma
Authors: Kelly Vanessa J. , Brown Nathan J. , Sands Scott A. , Borg Brigitte M. , King Gregory G. , Thompson Bruce R.
Published: February 2012

Airway distensibility appears to be unaffected by airway smooth muscle (ASM) tone, despite the influence of ASM tone on the airway diameter-pressure relationship. This discrepancy may be because the greatest effect of ASM tone on airway diameter-pressure behavior occurs at low transpulmonary pressures, i.e., low lung volumes, which has not been investigated. Our study aimed to determine the contribution of ASM tone to airway distensibility, as assessed via the forced oscillation technique (FOT), across all lung volumes with a specific focus on low lung volumes. We also investigated the accompanying influence of ASM tone on peripheral airway closure and heterogeneity inferred from the reactance versus lung volume relationship. Respiratory system conductance and reactance were measured using FOT across the entire lung volume range in 22 asthma subjects and 19 healthy controls before and after bronchodilator. Airway distensibility (slope of conductance vs. lung volume) was calculated at residual volume (RV), functional residual capacity (FRC), and total lung capacity. At baseline, airway distensibility was significantly lower in subjects with asthma at all lung volumes. After bronchodilator, distensibility significantly increased at RV (64.8%, P < 0.001) and at FRC (61.8%, P < 0.01) in subjects with asthma but not in control subjects. The increased distensibility at RV and FRC in asthma were not associated with the accompanying changes in the reactance versus lung volume relationship. Our findings demonstrate that, at low lung volumes, ASM tone reduces airway distensibility in adults with asthma, independent of changes in airway closure and heterogeneity.
Sphingomyelinase depresses force and calcium sensitivity of the contractile apparatus in mouse diaphragm muscle fibers
Authors: Ferreira Leonardo F. , Moylan Jennifer S. , Stasko Shawn , Smith Jeffrey D. , Campbell Kenneth S. , Reid Michael B.
Published: February 2012

Diseases that result in muscle weakness, e.g., heart failure, are characterized by elevated sphingomyelinase (SMase) activity. In intact muscle, SMase increases oxidants that contribute to diminished muscle force. However, the source of oxidants, specific processes of muscle contraction that are dysfunctional, and biochemical changes underlying the weakness elicited by SMase remain unknown. We tested three hypotheses: 1) SMase-induced depression of muscle force is mediated by mitochondrial reactive oxygen species (ROS), 2) SMase depresses force and calcium sensitivity of the contractile apparatus, and 3) SMase promotes oxidation and phosphorylation of myofibrillar proteins. Our experiments included intact muscle bundles, permeabilized single fibers, and isolated myofibrillar proteins. The mitochondrial-targeted antioxidant d-Arg-2′,6′-dimethyl-Tyr-Lys-Phe-NH2, decreased cytosolic oxidants and protected intact muscle bundles from weakness stimulated by SMase. SMase depressed maximal calcium-activated force by 20% in permeabilized single fibers (in kN/m2: control 117 ± 6; SMase 93 ± 8; P < 0.05). Calcium sensitivity of permeabilized single fibers decreased from 5.98 ± 0.03 (control) to 5.91 ± 0.02 (SMase; P < 0.05). Myofibrillar protein nitrotyrosines, carbonyls, and phosphorylation were unaltered by SMase. Our study shows that the fall in specific force of intact muscle elicited by SMase is mediated by mitochondrial ROS and can be attributed largely to dysfunction of the contractile apparatus.
Protein Kinase C Isoform ε Negatively Regulates ADP-Induced Calcium Mobilization and Thromboxane Generation in Platelets
Authors: Bynagari-Settipalli Yamini S. , Lakhani Parth , Jin Jianguo , Bhavaraju Kamala , Rico Mario C. , Kim Soochong , Woulfe Donna , Kunapuli Satya P.
Published: February 2012

Objective—

Members of the protein kinase C (PKC) family are shown to positively and negatively regulate platelet activation. Although positive regulatory roles are extensively studied, negative regulatory roles of PKCs are poorly understood. We investigated the mechanism and specific isoforms involved in PKC-mediated negative regulation of ADP-induced functional responses.

Methods and Results—

A pan-PKC inhibitor, GF109203X, potentiated ADP-induced cPLA
2
phosphorylation and thromboxane generation as well as ERK activation and intracellular calcium (Ca
2+
i
) mobilization, 2 signaling molecules, upstream of cPLA
2
activation. Thus, PKCs inhibit cPLA
2
activation by inhibiting ERK and Ca
2+
i
mobilization. Because the inhibitor of classic PKC isoforms, GO-6976, did not affect ADP-mediated thromboxane generation, we investigated the role of novel class of PKC isoforms. ADP-induced thromboxane generation, calcium mobilization, and ERK phosphorylation were potentiated in PKCε null murine platelets compared with platelets from wild-type littermates. Interestingly, when thromboxane release is blocked, ADP-induced aggregation in PKCε knockout and wild-type was similar, suggesting that PKCε does not affect ADP-induced aggregation directly. PKCε knockout mice exhibited shorter times to occlusion in an FeCl
3
-induced arterial injury model and shorter bleeding times in tail-bleeding experiments.

Conclusion—

We conclude that PKCε negatively regulates ADP-induced thromboxane generation in platelets and offers protection against thrombosis.
Substrate-Immobilized HIV-1 Tat Drives VEGFR2/α
v
β
3
–Integrin Complex Formation and Polarization in Endothelial Cells
Authors: Urbinati Chiara , Ravelli Cosetta , Tanghetti Elena , Belleri Mirella , Giacopuzzi Edoardo , Monti Eugenio , Presta Marco , Rusnati Marco
Published: February 2012

Objective—

The HIV-1 transactivating factor (Tat) possesses features typical of both cell-adhesive and angiogenic growth factor (AGF) proteins, inducing endothelial cell (EC) adhesion and proangiogenic activation. Tat was exploited to investigate the events triggered by EC adhesion to substrate-bound AGF that lead to proangiogenic activation.

Methods and Results—

Immobilized Tat induces actin cytoskeleton organization, formation of α
v
β
3
integrin
+
focal adhesion plaques, and recruitment of vascular endothelial growth factor receptor-2 (VEGFR2) in the ventral plasma membrane of adherent ECs. Also, acceptor photobleaching fluorescence resonance energy transfer demonstrated that VEGFR2/α
v
β
3
coupling occurs at the basal aspect of Tat-adherent ECs. Cell membrane fractionation showed that a limited fraction of α
v
β
3
integrin and VEGFR2 does colocalize in lipid rafts at the basal aspect of Tat-adherent ECs. VEGFR2 undergoes phosphorylation and triggers pp60src/ERK
1/2
activation. The use of lipid raft disrupting agents and second messenger inhibitors demonstrated that intact lipid rafts and the VEGFR2/pp60src/ERK
1/2
pathway are both required for cytoskeleton organization and proangiogenic activation of Tat-adherent ECs.

Conclusion—

Substrate-immobilized Tat causes VEGFR2/α
v
β
3
complex formation and polarization at the basal aspect of adherent ECs, VEGFR2/pp60src/ERK
1/2
phosphorylation, cytoskeleton organization, and proangiogenic activation. These results provide novel insights in the AGF/tyrosine kinase receptor/integrin cross-talk.
Antithrombin-Independent Effects of Heparins on Fibrin Clot Nanostructure
Authors: Yeromonahos Christelle , Marlu Raphaël , Polack Benoît , Caton Francois
Published: February 2012

Objective—

Because of the widespread clinical use of heparins, their effects on the enzymatic cascade are very well known. In contrast, little is known about the direct effect of heparins on the nanostructure of fibrin fibers, even though this nanostructure plays a major role in the mechanical strength and lysis of clots. This lack of reliable data can be correlated with the lack of a nonintrusive, quantitative method to determine this structure. We recently developed such a method that allows the simultaneous determination of the average fiber radius and the protein content using spectrometric data. In this study, we assessed the nanostructure of fibrin in a system composed of human thrombin and fibrinogen.

Methods and Results—

We provide quantitative evidence showing that both unfractionated heparin and low molecular weight heparin directly alter the nanostructure of fibrin fibers independent of their other actions on the coagulation cascade; as expected, the pentasaccharide fondaparinux has no effect.

Conclusion—

Our results show that in addition to the effect of heparin on the coagulation cascade, modifications of the fibrin nanostructure may also contribute to improved fibrinolysis.
Serum Levels of Vitamin E Are Associated With Early Recurrence of Atrial Fibrillation After Electric Cardioversion
Authors: Ferro Domenico , Franciosa Pasquale , Cangemi Roberto , Carnevale Roberto , Pignatelli Pasquale , Loffredo Lorenzo , Perri Ludovica , Catasca Elisa , Violi Francesco
Published: February 2012

Background—

Oxidative stress is suggested to play a role in favoring the occurrence of atrial fibrillation (AF). We analyzed whether vitamin E, a known antioxidant, or markers of oxidative stress are associated with AF recurrence in patients undergoing electric cardioversion.

Methods and Results—

A total of 144 patients (83 men; mean age, 71.1±5.4 years) underwent successful biphasic electric cardioversion of nonvalvular persistent AF. At baseline, urinary 8-isoprostaglandin F2α and serum soluble NOX2-derived peptide (sNOX2-dp), high-sensitivity C-reactive protein (hs-CRP), and vitamin E levels were measured in each patient. All patients underwent 3 months of clinical follow-up, including an office visit with ECG every week or in cases of symptom recurrence. During the follow-up, 94 patients maintained sinus rhythm, whereas 50 experienced AF recurrence. In unadjusted analysis, left atrial diameter and levels of urinary isoprostanes and serum sNOX2-dp and hs-CRP were significantly higher and serum vitamin E lower in patients with AF recurrence. In multivariable Cox analysis, serum vitamin E (hazard ratio, 0.734; 95% CI, 0.605–0.891;
P
<0.001) and, to a lesser extent, hs-CRP (
P
=0.047) remained significantly associated with AF recurrence. Urinary isoprostanes and serum sNOX2-dp levels were inversely correlated with serum vitamin E level (
r
=−0.626,
P
<0.001, and
r
=−0.460,
P
<0.001, respectively).

Conclusions—

The study shows that low serum vitamin E levels are associated with AF recurrence in patients who underwent cardioversion. Because vitamin E inversely correlated with oxidative stress, the findings reinforce the hypothesis of an interplay between oxidative stress and AF.
Determinants of Left Ventricular Mass in Patients on Hemodialysis
Authors: Chan Christopher T. , Greene Tom , Chertow Glenn M. , Kliger Alan S. , Stokes John B. , Beck Gerald J. , Daugirdas John T. , Kotanko Peter , Larive Brett , Levin Nathan W. , Mehta Ravindra L. , Rocco Michael , Sanz Javier , Schiller Brigitte M. , Yang Phillip C. , Rajagopalan Sanjay ,   the Frequent Hemodialysis Network (FHN) Trial Group
Published: February 2012

Background—

An increase in left ventricular mass (LVM) is associated with mortality and cardiovascular morbidity in patients with end-stage renal disease.

Methods and Results—

The Frequent Hemodialysis Network (FHN) Daily Trial randomized 245 patients to 12 months of 6 times per week daily in-center hemodialysis or conventional hemodialysis; the FHN Nocturnal Trial randomized 87 patients to 12 months of 6 times per week nocturnal hemodialysis or conventional hemodialysis. The main cardiac secondary outcome was change in LVM. In each trial, we examined whether several predefined baseline demographic or clinical factors as well as change in volume removal, blood pressure, or solute clearance influenced the effect of frequent hemodialysis on LVM. In the Daily Trial, frequent hemodialysis resulted in a significant reduction in LVM (13.1 g; 95% CI, 5.0–21.3 g;
P
=0.002), LVM index (6.9 g/m
2
; 95% CI, 2.4–11.3 g/m
2
;
P
=0.003), and percent change in geometric mean of LVM (7.0%; 95% CI, 1.0%–12.6;
P
=0.02). Similar trends were noted in the Nocturnal Trial but did not reach statistical significance. In the Daily Trial, a more pronounced effect of frequent hemodialysis on LVM was evident among patients with left ventricular hypertrophy at baseline. Changes in LVM were associated with changes in blood pressure (conventional hemodialysis:
R
=0.28,
P
=0.01, daily hemodialysis:
R
=0.54,
P
<0.001) and were not significantly associated with changes in other parameters.

Conclusions—

Frequent in-center hemodialysis reduces LVM. The benefit of frequent hemodialysis on LVM may be mediated by salutary effects on blood pressure.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00264758.
Prediction of Long-Term Mortality After Percutaneous Coronary Intervention in Older Adults
Authors: Weintraub William S. , Grau-Sepulveda Maria V. , Weiss Jocelyn M. , DeLong Elizabeth R. , Peterson Eric D. , O'Brien Sean M. , Kolm Paul , Klein Lloyd W. , Shaw Richard E. , McKay Charles , Ritzenthaler Laura L. , Popma Jeffrey J. , Messenger John C. , Shahian David M. , Grover Frederick L. , Mayer John E. , Garratt Kirk N. , Moussa Issam D. , Edwards Fred H. , Dangas George D.
Published: February 2012

Background—

The purpose of this study was to develop a long-term model to predict mortality after percutaneous coronary intervention in both patients with ST-segment elevation myocardial infarction and those with more stable coronary disease.

Methods and Results—

The American College of Cardiology Foundation CathPCI Registry data were linked to the Centers for Medicare and Medicaid Services 100% denominator file by probabilistic matching. Preprocedure demographic and clinical variables from the CathPCI Registry were used to predict the probability of death over 3 years as recorded in the Centers for Medicare and Medicaid Services database. Between 2004 and 2007, 343 466 patients (66%) of 518 195 patients aged ≥65 years undergoing first percutaneous coronary intervention in the CathPCI Registry were successfully linked to Centers for Medicare and Medicaid Services data. This study population was randomly divided into 60% derivation and 40% validation cohorts. Median follow-up was 15 months, with mortality of 3.0% at 30 days and 8.7%, 13.4%, and 18.7% at 1, 2, and 3 years, respectively. Twenty-four characteristics related to demographics, clinical comorbidity, prior history of disease, and indices of disease severity and acuity were identified as being associated with mortality. The C indices in the validation cohorts for patients with and without ST-segment elevation myocardial infarction were 0.79 and 0.78. The model calibrated well across a wide range of predicted probabilities.

Conclusions—

On the basis of the large and nationally representative CathPCI Registry, we have developed a model that has excellent discrimination, calibration, and validation to predict survival up to 3 years after percutaneous coronary intervention.
Interleukin-1β Is Crucial for the Induction of Coronary Artery Inflammation in a Mouse Model of Kawasaki Disease
Authors: Lee Youngho , Schulte Danica J. , Shimada Kenichi , Chen Shuang , Crother Timothy R. , Chiba Norika , Fishbein Michael C. , Lehman Thomas J.A. , Arditi Moshe
Published: February 2012

Background—

Kawasaki disease (KD) is the most common cause of acute vasculitis and acquired cardiac disease in US children. Untreated, children may develop coronary artery aneurysms, myocardial infarction, and sudden death as a result of the illness. Up to a third of KD patients fail to respond to intravenous immunoglobulin, the standard therapy, and alternative treatments are being investigated. Genetic studies have indicated a possible role for interleukin (IL)-1β in KD. We therefore explored the role of IL-1β in a murine model of KD.

Methods and Results—

Using an established mouse model of KD that involves injection of
Lactobacillus casei
cell wall extract (LCWE), we investigated the role of IL-1β and caspase-1 (activated by the inflammasome and required for IL-1β maturation) in coronary arteritis and evaluated the efficacy of IL-1 receptor antagonist as a potential treatment. LCWE-induced IL-1β maturation and secretion were dependent on the NLRP3 inflammasome in macrophages. Both caspase-1–deficient and IL-1 receptor–deficient mice were protected from LCWE-induced coronary lesions. Injection of recombinant IL-1β into caspase-1–deficient mice restored the ability of LCWE to cause coronary lesions in response to LCWE. Furthermore, daily injections of the IL-1 receptor antagonist prevented LCWE-mediated coronary lesions up to 3 days after LCWE injection.

Conclusions—

Our results strongly suggest that caspase-1 and IL-1β play critical roles in the development of coronary lesions in this KD mouse model, blocked by IL-1 receptor antagonist. Therefore, anti–IL-1β treatment strategies may constitute an effective, more targeted treatment of KD to prevent coronary lesions.
Postradiosurgery Hemorrhage Rates of Arteriovenous Malformations of the Brain
Authors: Parkhutik Vera , Lago Aida , Tembl José Ignacio , Vázquez Juan Francisco , Aparici Fernando , Mainar Esperanza , Vázquez Víctor
Published: February 2012

Background and Purpose—

The long-term benefit of radiosurgery of brain arteriovenous malformations (AVM), especially nonhemorrhagic cases, is controversial. We calculated hemorrhage rates pre- and posttreatment and analyzed the risk factors for bleeding based on cases followed at our site.

Methods—

One hundred eight patients, age 36±17 years, 56 men. The mean follow-up was 65±44 months (median, 54; interquartile range, 33–94). Most AVMs were small (74.1% <3 cm in diameter); 48.1% were located in an eloquent area, 27.8% had deep drainage, and 39.8% presented with hemorrhage.

Results—

The annual hemorrhage rate for any undiagnosed AVM was 1.2%, and 3.3% for AVMs with hemorrhagic presentation. Older patients, cortical or subcortical AVMs, and cases with multiple draining veins were less likely to present with bleeding. During the first 36 months postradiosurgery, hemorrhagic AVMs had a rebleeding rate of 2.1%, and a rate of 1.1% from 3 years onwards. Nonhemorrhagic AVMs had a hemorrhage rate of 1.4% during the first 3 years and 0.3% afterward. Arterial hypertension and nidus volume were independent predictors of bleeding after treatment. Mean nidus obliteration time was 37±18 months (median, 32; interquartile range, 25–40), with hemorrhage rate of 1.3% before and 0.6% after obliteration, and 1.9% for AVMs that were not closed at the end of follow-up.

Conclusions—

Both hemorrhagic and nonhemorrhagic AVMs benefit from radiosurgical therapy, with gradual decrease in their bleeding rates over the years. Albeit small, the risk of hemorrhage persists during the entirety of follow-up, being higher for cases with hemorrhagic presentation and nonobliterated AVM.
Dietary Flavonoids and Risk of Stroke in Women
Authors: Cassidy Aedín , Rimm Eric B. , O'Reilly Éilis J. , Logroscino Giancarlo , Kay Colin , Chiuve Stephanie E. , Rexrode Kathryn M.
Published: February 2012

Background and Purpose—

To date, few studies have examined associations between the wide range of flavonoid subclasses and risk of ischemic, hemorrhagic, and total stroke.

Methods—

We conducted a prospective study among 69 622 women from the Nurses' Health Study. Total flavonoid and subclass intakes were calculated from semiquantitative food frequency questionnaires collected every 4 years using an updated and extended US Department of Agriculture flavonoid database.

Results—

During 14 years of follow-up, 1803 incident strokes were confirmed. After adjusting for potential confounders, women in the highest compared with the lowest quintile of flavanone intake had a relative risk of ischemic stroke of 0.81 (95% CI, 0.66–0.99;
P
=0.04). Citrus fruits/juices, the main dietary source of flavanones, tended to be associated with a reduced risk for ischemic stroke (relative risk, 0.90; 95% CI, 0.77–1.05) comparing extreme quintiles.

Conclusions—

Total flavonoid intake was not inversely associated with risk of stroke; however, increased intake of the flavanone subclass was associated with a reduction in the risk of ischemic stroke. Citrus fruit consumption may be associated with a reduction in stroke risk, and experimental data support these epidemiological associations that the flavanone content of citrus fruits may potentially be cardioprotective. Further prospective studies are needed to confirm these associations.
Socioeconomic Status and Stroke
Authors: Addo Juliet , Ayerbe Luis , Mohan Keerthi M. , Crichton Siobhan , Sheldenkar Anita , Chen Ruoling , Wolfe Charles D.A. , McKevitt Christopher
Published: February 2012

Background and Purpose—

Rates of stroke incidence and mortality vary across populations with important differences between socioeconomic groups worldwide. Knowledge of existing disparities in stroke risk is important for effective stroke prevention and management strategies. This review updates the evidence for associations between socioeconomic status and stroke.

Summary of Review—

Studies were identified with electronic searches of MEDLINE and EMBASE databases (January 2006 to July 2011) and reference lists from identified studies were searched manually. Articles reporting the association between any measure of socioeconomic status and stroke were included.

Conclusions—

The impact of stroke as measured by disability-adjusted life-years lost and mortality rates is >3-fold higher in low-income compared with high- and middle-income countries. The number of stroke deaths is projected to increase by >30% in the next 20 years with the majority occurring in low-income countries. Higher incidence of stroke, stroke risk factors, and rates of stroke mortality are generally observed in low compared with high socioeconomic groups within and between populations worldwide. There is less available evidence of an association between socioeconomic status and stroke recurrence or temporal trends in inequalities. Those with a lower socioeconomic status have more severe deficits and are less likely to receive evidence-based stroke services, although the results are inconsistent. Poorer people within a population and poorer countries globally are most affected in terms of incidence and poor outcomes of stroke. Innovative prevention strategies targeting people in low socioeconomic groups are required along with effective measures to promote access to effective stroke interventions worldwide.
Hemodynamic Differences Between Unruptured and Ruptured Intracranial Aneurysms During Observation
Authors: Takao Hiroyuki , Murayama Yuichi , Otsuka Shinobu , Qian Yi , Mohamed Ashraf , Masuda Shunsuke , Yamamoto Makoto , Abe Toshiaki
Published: February 2012

Background and Purpose—

We evaluated several hemodynamic parameters for the prediction of rupture in a data set of initially unruptured aneurysms, including aneurysms that ruptured during follow-up observation.

Methods—

Aneurysm geometry was extracted from CT angiographic images and analyzed using a mathematical formula for fluid flow under pulsatile blood flow conditions. Fifty side-wall internal carotid posterior communicating artery aneurysms and 50 middle cerebral artery bifurcation aneurysms of medium size were investigated for energy loss, pressure loss coefficient, wall shear stress, and oscillatory shear index. During follow-up observation, 6 internal carotid posterior communicating artery and 7 middle cerebral artery aneurysms ruptured (44 and 43 remained unruptured, respectively, with the same location and a similar size as the ruptured cases).

Results—

A significant difference in the minimum wall shear stress between aneurysms that ruptured and those that remained unruptured was noted only in internal carotid artery aneurysms (
P
<0.001). Energy loss showed a higher tendency in ruptured aneurysms but statistically not significant. For pressure loss coefficient, a significant difference was noted in both internal carotid artery (
P
=0.0046) and middle cerebral artery (
P
<0.001) aneurysms.

Conclusions—

Pressure loss coefficient may be a potential parameter to predict future rupture of unruptured aneurysms.