bluuebunny/crossref_metadata_2025 huggingface dataset:
Preparation of SiO2Nanotubes with Controllable Inner/Outer Diameter and Length Using Hydrothermally Grown ZnO Nanowires as Templates
Authors: Kuo Der-Ming , Wang Shui-Jinn , Uang Kai-Ming , Chen Tron-Min , Tsai Wei-Chih , Hsu Wen-I , Lee Wei-Chi , Wang Pei-Ren , Tseng Chih-Ren
Published: April 2010

Through the deposition of a thin SiO2film to sheathe hydrothermally grown (HTG) ZnO nanowires (ZnO-NWs), unveiling their top portion, and then selectively removing ZnO-NWs by wet chemical etching, SiO2nanotubes (SiO2-NTs) with controllable inner/outer diameters and lengths were fabricated. The prepared SiO2-NTs with average inner/outer diameters and lengths of approximately 200/300 nm and 1.5 µm, respectively, exhibited a superior transmittance of 92% in the visible light spectrum. The surface roughened process using SiO2-NTs on vertical-structure GaN light-emitting diodes (VLEDs) showed additional light output improvement of about 11.6% at 350 mA and 10% at 750 mA, compared with those of VLEDs with ZnO-NWs, suggesting the effectiveness and promising applications of the proposed SiO2-NTs in optics and optoelectronics devices.
Computational Investigation of Relationship between Shear Stress and Multicrystalline Structure in Silicon
Authors: Takahashi Isao , Usami Noritaka , Kutsukake Kentaro , Morishita Kohei , Nakajima Kazuo
Published: April 2010

We performed computational calculations by three-dimensional finite element analysis to investigate the relationship between the shear stress on slip planes and multicrystalline structural properties in Si, such as the grain orientation and the structure of the grain boundary. In our calculations, the change in multicrystalline structure is defined as the change in anisotropic elastic coefficient, which depends on the grain orientation. As a result, it becomes clear that the shear stress on slip planes depends on the grain orientation and concentrates near the grain boundary. Calculations in various multicrystalline structures reveal that controlling the growth direction in <100> or <110> has a great advantage for decreasing the shear stress on slip planes and resulting in the suppression of dislocation occurrence.
A New Approach Using Backside Scatterers for Efficiency Enhancement in Thin Si Solar Cells
Authors: Yanai Akihiro , Ichikawa Ryuzo , Ishikawa Yasuhiko , Wada Kazumi
Published: April 2010

In order to increase the optical path length in thin Si solar cells for the efficiency enhancement, we examined a method to use scatterers of air spheres on the 10 nm scale. The air spheres were randomly embedded on the backside of solar cell to cause the Rayleigh scattering. The incident solar light propagates in the lateral direction after the scattering, increasing the optical path length much longer than the cell thickness. According to the simulations, the light was found to be sufficiently absorbed due to the scattering even for the wavelength over 1100 nm, which is difficult to be absorbed in ordinary thin Si cells. In experiments, air holes in a porous Si layer were examined as the scattering sources, showing the behavior similar to the simulation result. These results suggest that the backside scatterers are useful for the efficiency enhancement in thin Si cells.
Lift-Off Process for Flexible Cu(In,Ga)Se2 Solar Cells
Authors: Minemoto Takashi , Abe Yasuhiro , Anegawa Takaya , Osada Shintaro , Takakura Hideyuki
Published: April 2010

A lift-off process for flexible Cu(In,Ga)Se2 (CIGS) solar cells was developed. After the growth of a CIGS thin film on a Mo/glass substrate at 550 °C, the CIGS film was transferred to polyimide and poly(tetrafluoroethylene) films. Process temperatures for the device fabrication after the transfer were less than 100 °C. The conversion efficiencies of the lift-off CIGS solar cells were similar and were almost one-half that of a CIGS solar cell prepared by a standard process. The difference was mainly due to the low fill factor caused by a poor back-contact property and the low short-circuit current caused by an inappropriate band gap profile in the CIGS layer. There still remain problems related to the improvement in efficiency; however, this is the first report on flexible CIGS solar cells on a low-thermal-tolerance substrate. We demonstrated the possibility of freedom of substrate material choice in CIGS solar cells.
Electronic Structure and Characteristics of Chemical Bonds in CuInSe2, CuGaSe2, and CuAlSe2
Authors: Maeda Tsuyoshi , Wada Takahiro
Published: April 2010

Electronic structural calculations of chalcopyrite-type CuInSe2 and its related compounds, CuGaSe2 and CuAlSe2, were performed by a recently proposed screened-exchange local density approximation (sX-LDA) method. The theoretical band gaps of CuInSe2, CuGaSe2, and CuAlSe2, obtained by the conventional calculation method using a generalized gradient approximation (GGA) functional, were 0.04, 0.14, and 1.11 eV, respectively. These values were considerably underestimated in comparison with their experimental values of 1.04, 1.68, and 2.67 eV because the exchange–correlation energy was not precisely calculated. Therefore, electronic structural calculations of chalcopyrite-type CuInSe2 and related compounds were performed with an sX-LDA functional to obtain accurate electronic structure. The present sX-LDA calculation successfully reproduced the band gaps of CuInSe2 (0.96 eV), CuGaSe2 (1.36 eV), and CuAlSe2 (2.22 eV). The obtained electronic structures and band gap energies of CuInSe2, CuGaSe2, and CuAlSe2 are discussed on the basis of schematic molecular orbital diagrams of tetrahedral CuSe4
7-, InSe4
5-, GaSe4
5-, and AlSe4
5- clusters.
A Theoretical Study on Initial Processes of Li-Ion Transport at the Electrolyte/Cathode Interface: A Quantum Chemical Molecular Dynamics Approach
Authors: Ogawa Tomaru , Miyano Masayuki , Suzuki Yasuhiro , Suzuki Ai , Tsuboi Hideyuki , Hatakeyama Nozomu , Endou Akira , Takaba Hiromitsu , Kubo Momoji , Miyamoto Akira
Published: April 2010

Initial processes of Li-ion transport at the electrolyte/cathode interface of a Li-ion battery were investigated using an ultra-accelerated quantum chemical molecular dynamics (UA-QCMD) simulator. This simulator was based on our in-house tight-binding quantum chemical (TB-QC) simulator and MD simulator. The parameterization for LiCoO2crystal and ethylene carbonate (EC) molecule in UA-QCMD was first carried out to show the fine agreement of their electronic structures and interaction energies, with the values determined by first-principles calculations. Li-ion movements in the electrolyte and at the interface between the electrolyte and cathode were simulated. It was found that in the electrolyte, a solvation, that corresponds to the formation of bonds between the Li and surrounded EC molecules was formed. When the Li-ion was moved to the cathode surface, it was observed that the interaction energies of Li-EC molecules was decreased. In such a case, the Li-ion was bound to the oxygen atoms of the cathode.
Analysis of Hot Carrier Degradation of Lateral Double-Diffused Metal–Oxide–Semiconductor under Gate Pulse Stress
Authors: Furuya Keiichi , Nitta Tetsuya , Katayama Toshiharu , Hatasako Kenichi , Kuroi Takashi , Maegawa Shigeto
Published: April 2010

The lateral double-diffused metal–oxide–semiconductor (LDMOS) transistor is one of the key elements of high-power devices. It is difficult to evaluate the degradation of an LDMOS at the required temperature range, because the self-heating effect of an LDMOS is too large for conventional evaluation in DC. In this paper, we report on the hot carrier degradation of an LDMOS under high-power operation, by investigating the LDMOS deterioration in the case that both the device structure and junction temperature (T
j) are different. The T
j of an LDMOS is controlled by operating the gate voltage (V
g) in pulse mode. Controlling T
j by operating V
g in pulse mode, the T
j dependence of hot carrier degradation under high-power operation can be evaluated widely and quantitatively. The threshold voltage (V
th) shift is observed according to the bias temperature mode irrespective of the device structure. On the other hand, the shift of drain current is affected by the length of the accumulation region under the gate electrode, and a relatively small increase in drain current (I
ds) shift is observed with decreasing T
j. These phenomena are clarified from the results of charge pumping measurement and simulation.
Current Distribution Analysis of Insulated Gate Bipolar Transistor Cells
Authors: Long Hongyao , Sweet Mark R. , Ngwendson Luther-King , Narayanan E. M. Sankara
Published: April 2010

In current insulated gate bipolar transistor (IGBT) technology, a corner or centered gate pad is employed with polycrystalline silicon (poly-Si) to form the metal oxide semiconductor (MOS) gate structure which forms a resistor–capacitor (RC) network across the die. This paper presents, for the first time, an analysis using circuit simulator, SABER, to analyze its influence on the internal behavior of the IGBT. The difference in the interconnect gate impedance between each cathode cells is found to influence their gate drive voltages, which results in the divergence of collector current within each cathode cells during transient periods. Proper distribution of the poly-Si gate impedance is necessary to achieve uniformity of current distribution in the device.
Cathodoluminescence Microcharacterization of Radiative Recombination Centers in Lifetime-Controlled Insulated Gate Bipolar Transistors
Authors: Sugie Ryuichi , Mitani Takeshi , Yoshikawa Masanobu , Iwata Yoshiharu , Satoh Ryohei
Published: April 2010

Cross-sectional cathodoluminescence (CL) measurements were applied to the study of electron-irradiated punch-through insulated gate bipolar transistors (IGBTs) to investigate the relationship between radiative recombination centers and electrical characteristics. IGBTs were additionally annealed at temperatures of 200–400 °C for 1 h. As annealing temperature rose, collector–emitter saturation voltage (V
CES) decreased and current fall time (t
f) increased. The cross-sectional CL measurements showed sharp luminescent peaks at 1018 meV (W or I1), 1040 meV (X or I3), and 790 meV (C) and a broad band at approximately 0.90–1.05 eV. As annealing temperature rose, the intensity of the W line decreased and that of the X line increased, suggesting that small self-interstitial clusters agglomerate and form stable, large self-interstitial clusters reducing the total number of self-interstitial clusters. The C line, which originated from an interstitial oxygen and carbon complex, showed no significant change. We consider that self-interstitial clusters play important roles in the electrical characteristics of lifetime-controlled IGBTs.
Characterization of the Lateral Distribution of Fluorescent Lipid in Binary‐Constituent Lipid Monolayers by Principal Component Analysis
Authors: Sugár István P. , Zhai Xiuhong , Boldyrev Ivan A. , Molotkovsky Julian G. , Brockman Howard L. , Brown Rhoderick E.
Published: April 2010

Lipid lateral organization in binary‐constituent monolayers consisting of fluorescent and nonfluorescent lipids has been investigated by acquiring multiple emission spectra during measurement of each force‐area isotherm. The emission spectra reflect BODIPY‐labeled lipid surface concentration and lateral mixing with different nonfluorescent lipid species. Using principal component analysis (PCA) each spectrum could be approximated as the linear combination of only two principal vectors. One point on a plane could be associated with each spectrum, where the coordinates of the point are the coefficients of the linear combination. Points belonging to the same lipid constituents and experimental conditions form a curve on the plane, where each point belongs to a different mole fraction. The location and shape of the curve reflects the lateral organization of the fluorescent lipid mixed with a specific nonfluorescent lipid. The method provides massive data compression that preserves and emphasizes key information pertaining to lipid distribution in different lipid monolayer phases. Collectively, the capacity of PCA for handling large spectral data sets, the nanoscale resolution afforded by the fluorescence signal, and the inherent versatility of monolayers for characterization of lipid lateral interactions enable significantly enhanced resolution of lipid lateral organizational changes induced by different lipid compositions.
Estimating Ground Inclination Using Strain Sensors with Fourier Series Representation
Authors: Svensson Wolfgang , Holmberg Ulf
Published: April 2010

An embedded measurement system for foot orthosis during gait is proposed. Strain gauge sensors were mounted on a foot orthosis to give information about strain in the sagittal plane. The ankle angle of the orthosis was fixed and strain characteristics were therefore changed when walking on slopes. With a Fourier series representation of the strain during a gait cycle, ground angle at different walking speeds and inclinations could be estimated with similar accuracy as previous studies using kinematically based estimators. Furthermore, if the angle of the mechanical foot ankle was changed, the sensing technique still could estimate ground angle without need for recalibration as opposed to kinematical sensors. This indicates that embedded strain sensors can be used for online control of future orthoses with inclination adaptation. Also, there would be no need to recalibrate the sensing system when changing shoes with different heel heights.
Occurrence and Sources of Triterpenoid Methyl Ethers and Acetates in Sediments of the Cross-River System, Southeast Nigeria
Authors: Oyo-Ita Orok E. , Ekpo Bassey O. , Oros Daniel R. , Simoneit Bernd R. T.
Published: April 2010

Pentacyclic triterpenol methyl ethers (PTMEs), germanicol methyl ether (miliacin), 3-methoxyfern-9(11)-ene (arundoin),β-amyrin methyl ether (iso-sawamilletin), and 3-methoxytaraxer-14-ene (sawamilletin or crusgallin) were characterized in surface sediments of the Cross-River system using gas chromatography-mass spectrometry (GC-MS). Triterpenol esters (mainlyα- andβ-amyrinyl acetates and hexanoates, and lupeyl acetate and hexanoate) were also found. These distinct compounds are useful for assessing diagenesis that can occur during river transport of organic detritus. Poaceae, mainly Gramineae andElaeis guineensishigher plant species, are proposed as primary sources for the PTMEs and esters in the sediments. PTMEs are biomarkers of specific higher plant subspecies, while the triterpenol esters are indicators of early diagenetic alteration of higher plant detritus.
Extending Conceptual Schemas with Business Process Information
Authors: Brambilla Marco , Cabot Jordi , Comai Sara
Published: April 2010

The specification of business processes is becoming a more and more critical aspect for organizations. Such processes are specified as workflow models expressing the logical precedence among the different business activities (i.e., the units of work). Typically, workflow models are managed through specific subsystems, called workflow management systems, to ensure a consistent behavior of the applications with respect to the organization business process. However, for small organizations and/or simple business processes, the complexity and capabilities of these dedicated workflow engines may be overwhelming. In this paper, we therefore, advocate for a different and lightweight approach, consisting in the integration of the business process specification within the system conceptual schema. We show how a workflow-extended conceptual schema can be automatically obtained, which serves both to enforce the organization business process and to manage all its relevant domain data in a unified way. This extended model can be directly processed with current CASE tools, for instance, to generate an implementation of the system (including its business process) in any technological platform.
Serum Levels of Natriuretic Peptides in Children before and after Treatment for an Atrial Septal Defect, a Patent Ductus Arteriosus, and a Coarctation of the Aorta—A Prospective Study
Authors: Eerola Anneli , Jokinen Eero , Boldt Talvikki , Mattila Ilkka P. , Pihkala Jaana I.
Published: April 2010

Background and Objectives. We evaluated and compared the influence of treatment for atrial septal defect (ASD), patent ductus arteriosus (PDA), and coarctation of the aorta (CoA) on serum levels of N-terminal proatriopeptide and N-terminal probrain natriuretic peptide. Correlations between peptide levels and echocardiographic measurements were calculated.Patients and Methods. Peptide levels were measured and echocardiography performed before and 6–12 months after treatment in 21 children with ASD, 25 with PDA, 15 with CoA, and 76 control children.Results. ANPN levels were higher than in controls at baseline in all patient groups, and NT-proBNP in patients with ASD and PDA. Both peptide levels were elevated 6 months after treatment and decreased thereafter. Peptide levels were higher in patients with volume than pressure overload. They correlated with echocardiographic measurements. At the 6-month follow-up, dimensions of the originally overloaded ventricle had normalized only in patients with PDA.Conclusions. After intervention, peptide levels decrease but normalization takes over 6 months. The type of correlation between peptide levels and echocardiography varies according to the loading condition. Measurement of peptide levels can be used for monitoring the course of a patient's heart disease.
An Asymptotic Approach for the Elastodynamic Problem of a Plate under Impact Loading
Authors: Michalopoulou Penelope , Papadopoulos George A.
Published: April 2010

An approach is presented for analyzing the transient elastodynamic problem of a plate under an impact loading. The plate is considered to be in the form of a long strip under plane strain conditions. The loading is taken as a concentrated line force applied normal to the plate surface. It is assumed that this line force is suddenly applied and maintained thereafter (i.e., it is a Heaviside step function of time). Inertia effects are taken into consideration and the problem is treated exactly within the framework of elastodynamic theory. The approach is based on multiple Laplace transforms and on certain asymptotic arguments. In particular, the one‐sided Laplace transform is applied to suppress time dependence and the two‐sided Laplace transform to suppress the dependence upon a spatial variable (along the extent of the infinite strip). Exact inversions are then followed by invoking the asymptotic Tauber theorem and the Cagniard‐deHoop technique. Various extensions of this basic analysis are also discussed.
Id1 Promotes Tumor Cell Migration in Nonsmall Cell Lung Cancers
Authors: Bhattacharya Raka , Kowalski Jeanne , Larson Allison R. , Brock Malcolm , Alani Rhoda M.
Published: April 2010

Id1, which belongs to the Id family of helix-loop-helix transcription factors has been most associated with tumor progression and metastatsis; however, its significance in lung cancers has not been extensively explored. Here we seek to evaluate the expression of Id1 in a pilot study of nonsmall-cell lung cancers (NSCLCs) and determine its diagnostic and functional significance in these tumors. Paired normal and malignant lung tissues as well as a panel of NSCLC primary tumors and cell lines were evaluated for Id1 expression using Western blotting and quantitative RT-PCR. Functional assays were performed to evaluate the role of Id1 in tumor cell growth, migration and progression. We find Id1 expression is upregulated in squamous cell carcinoma when compared to adenocarcinoma of the lung and that expression of Id1 versus the normal control is variable in NSCLCs. We also note that Id1 expression in NSCLC cells is largely growth factor dependant and constitutive expression of Id1 in NSCLC cells significantly increases tumor cell migration without affecting cell proliferation. We conclude that Id1, as a mediator of tumor cell migration, may be an indicator of aggressive potential in nonsmall-cell lung cancers.
High-Frequency Properties of Embedded Passives and Thermal Resistance in Organic Substrates for RF Module
Authors: Kondo Yusuke , Shimada Yasushi , Hirata Yoshitaka , Yamamoto Kazunori , Watanabe Etsuo , Kuriyama Akira
Published: April 2010

Radio Frequency (RF) modules have been miniaturized to meet the demand for smaller and more enhanced handsets for wireless applications such as cellular phones. However, area for passive devices used in RF modules has made further miniaturization difficult. Passives embedded in substrates are now being studied intensively. In addition, circuit simulation technology has been developed that enables efficient designing of RF module circuits. Circuit designers, however, have limited database of organic substrates and embedded passives. Further, optimized thermal designs are required to prevent thermal resistance increase due to miniaturization of substrates.
In this paper, we describe the high-frequency properties of the capacitors embedded in the organic substrates and present the equivalent circuit models of the embedded capacitors. We also present the thermal design of organic substrates applicable to RF modules.
Insulin-like Growth Factor 2 Expression Modulates Taxol Resistance and Is a Candidate Biomarker for Reduced Disease-Free Survival in Ovarian Cancer
Authors: Huang Gloria S. , Brouwer-Visser Jurriaan , Ramirez Marissa J. , Kim Christine H. , Hebert Tiffany M. , Lin Juan , Arias-Pulido Hugo , Qualls Clifford R. , Prossnitz Eric R. , Goldberg Gary L. , Smith Harriet O. , Horwitz Susan Band
Published: April 2010

Purpose: This study was undertaken to examine the role of the insulin-like growth factor (IGF) signaling pathway in the response of ovarian cancer cells to Taxol and to evaluate the significance of this pathway in human epithelial ovarian tumors.

Experimental Design: The effect of Taxol treatment on AKT activation in A2780 ovarian carcinoma cells was evaluated using antibodies specific for phospho-AKT. To study the drug-resistant phenotype, we developed a Taxol-resistant cell line, HEY-T30, derived from HEY ovarian carcinoma cells. IGF2 expression was measured by real-time PCR. A type 1 IGF receptor (IGF1R) inhibitor, NVP-AEW541, and IGF2 small interfering RNA were used to evaluate the effect of IGF pathway inhibition on proliferation and Taxol sensitivity. IGF2 protein expression was evaluated by immunohistochemistry in 115 epithelial ovarian tumors and analyzed in relation to clinical/pathologic factors using the χ2 or Fisher's exact tests. The influence of IGF2 expression on survival was studied with Cox regression.

Results: Taxol-induced AKT phosphorylation required IGF1R tyrosine kinase activity and was associated with upregulation of IGF2. Resistant cells had higher IGF2 expression compared with sensitive cells, and IGF pathway inhibition restored sensitivity to Taxol. High IGF2 tumor expression correlated with advanced stage (P < 0.001) and tumor grade (P < 0.01) and reduced disease-free survival (P < 0.05).

Conclusions: IGF2 modulates Taxol resistance, and tumor IGF2 expression is a candidate prognostic biomarker in epithelial ovarian tumors. IGF pathway inhibition sensitizes drug-resistant ovarian carcinoma cells to Taxol. Such novel findings suggest that IGF2 represents a therapeutic target in ovarian cancer, particularly in the setting of Taxol resistance. Clin Cancer Res; 16(11); 2999–3010. ©2010 AACR.
Regulation of Multilineage Gene Expression and Apoptosis during in vitro Expansion of Human Bone Marrow Stromal Cells with Different Cell Culture Media
Authors: Zhu Huiyong , Miosge Nicolai , Schulz Jutta , Schliephake Henning
Published: April 2010

The aim of the present study was to analyze the effect of 3 different expansion media on the expression of marker genes of mesenchymal differentiation (bone, cartilage, fat) as well as apoptosis and senescence during repeated passaging in human bone marrow stromal cells (hBMSCs) in order to identify potential expansion strategies for the use of these cells into tissue-engineered growth of bone. Medium 1 (EGF, PDGF, low Glc, 2% FCS) was associated with the highest proliferation rate compared to medium 2 (β-mercaptoethanol, high Glc DMEM, 15% FCS) and medium 3 (low Glc DMEM, 10% FCS). Real time RT-PCR indicated the lowest levels of expression of osteonectin, core binding factor-α 1, lipoprotein lipase and cartilage oligo matrix protein in medium-1 cultures as compared to media 2 and 3. Early passages expressed higher levels of peroxisome proliferator-activator receptor-γ2 in medium 1 than in media 2 and 3, whereas no difference of Sox-9 expression was noticed among the 3 media. Expression of apoptosis- and senescence-related genes (Bax, BCL-2 and P16INK4a) exhibited the lowest level of Bax/BCL-2 ratio and P16INK4a gene expression of hBMSC in medium 1. In conclusion, the replacement of FCS by recombinant EGF and PDGF promoted rapid proliferation of hBMSCs without inducing differentiation of hBMSCs. It also inhibited expression of apoptosis-related genes and limited replicative senescence during repeated passaging. Media with the lowest possible FCS content and replacement by EGF and PDGF thus should be used for 2D culturing during expansion of hBMSCs, whereas β-mercaptoethanol and high concentrations of FCS can help to commence osteogenic differentiation.
Slow Cooling Cryopreservation of Cell-Microcarrier Constructs
Authors: Lippens Evi , Cornelissen Maria
Published: April 2010

Ideally, tissue engineered constructs should be readily available to meet the need for fast intervention in complex bone defects. To circumvent the long culture period of these constructs before implantation, we investigated the possibility of cryopreserving cell-loaded constructs. Goat bone marrow-derived mesenchymal stem cells (BMSC) and mouse osteoblast-like cells from the MC3T3-E1 cell line were cultured on gelatin CultiSpher-S® microcarriers. These constructs were cryopreserved using the slow cooling technique, i.e. cooling to –80°C at a rate of –1.5°C/min, and were then stored in liquid nitrogen for 1 week. Four different cryomedia were tested, i.e. 90 vol% serum with 10 vol% dimethylsulphoxide (Me2SO) with or without ascorbic acid (AA) and 90 vol% serum supplemented with 5 vol% Me2SO and 5 vol% hydroxyethyl starch or 5 vol% sucrose (60 mM). Cell viability on the constructs was assessed with fluorescent live/dead staining and the colorimetric MTS assay. Cell viability was compared before freezing and at fixed time points after thawing. Immediately after thawing, the viability percentages in all groups were significantly lower than before cryopreservation (p = 0.0369). No significant differences were observed between the viability percentages on the cell constructs cryopreserved in the different media; however, there was a general tendency for higher cell survival and faster recolonization of constructs cryopreserved in Me2SO with or without AA than of the constructs cryopreserved in the other media. For constructs cryopreserved in 10 vol% Me2SO with or without AA, the recolonization period was 3 days for the BMSC constructs and 3.6 and 3.8 days, respectively, for the MC3T3-E1 constructs.
A Dose Escalation Trial of Biweekly Docetaxel and Gemcitabine with Filgrastim or Pegfilgrastim for the Treatment of Patients with Advanced Solid Tumors
Authors: Dragnev Konstantin H. , Hardin Steven B. , Pipas J. Marc , Davis Thomas H. , Rigas James R.
Published: April 2010

Background/Aims: A single-institution phase I trial to determine the feasibility of using filgrastim or pegfilgrastim to increase the dose intensity of biweekly docetaxel and gemcitabine. Methods: Patients with metastatic solid tumors received gemcitabine 3,000 mg/m2 and increasing doses of docetaxel (55 mg/m2 in 10 mg/m2 increments) every 14 days with filgrastim or pegfilgrastim. Results: 35 patients enrolled, median 2 prior therapies, 158 cycles of therapy. There was 1 dose-limiting toxicity (DLT) (sepsis) at docetaxel 55 mg/m2, 1 DLT (sepsis/diarrhea) at docetaxel 65 mg/m2, and no DLT at docetaxel 75 mg/m2. At docetaxel 85 mg/m2, 2/4 patients had DLT (fatigue/dyspnea, diarrhea). The maximum tolerated dose (MTD) of docetaxel was 75 mg/m2. 1/12 patients treated at MTD experienced DLT (sepsis/dyspnea). The initial 25 patients received filgrastim (average 7 doses/cycle), the last 10 received pegfilgrastim. Conclusions: The MTD for docetaxel was 75 mg/m2 with gemcitabine 3,000 mg/m2 given every 14 days with filgrastim or pegfilgrastim. This regimen was well tolerated with signs of clinical activity. We found no significant differences in toxicities or effectiveness between daily filgrastim and pegfilgrastim given 13 days before the next chemotherapy. The use of granulocyte growth factors allowed increased dose intensity of docetaxel and gemcitabine. This regimen warrants further study in chemotherapy-naïve patients and patients with earlier stages.
Mapping and Ablation of Epicardial Idiopathic Ventricular Arrhythmias From Within the Coronary Venous System
Authors: Baman Timir S. , Ilg Karl J. , Gupta Sanjaya K. , Good Eric , Chugh Aman , Jongnarangsin Krit , Pelosi Frank , Ebinger Matthew , Crawford Thomas , Oral Hakan , Morady Fred , Bogun Frank
Published: April 2010

Background—

The prevalence of epicardial idiopathic ventricular arrhythmias that can be ablated from within the coronary venous system (CVS) has not been described.

Methods and Results—

In a consecutive group of 189 patients with idiopathic ventricular arrhythmias referred for ablation, the site of origin (SOO) of ventricular tachycardia and/or premature ventricular contractions was determined by activation mapping and pace mapping. Mapping was performed within the CVS if endocardial mapping did not reveal an SOO. Venography of the CVS and coronary angiography were performed before ablation in the CVS. In 27 of 189 patients (14%±5%; 95% confidence interval), the SOO of the ventricular arrhythmia was identified from within the coronary venous system, either in the great cardiac vein (n=26) or the middle cardiac vein (n=1). The mean activation time at the SOO was −29±8 ms. Twenty of 27 patients (74%) underwent successful ablation within the CVS. Epicardial ventricular arrhythmias displayed a broader R wave in V
1
compared with arrhythmias in the control group (85 ms [interquartile range, 40] versus 65 ms [interquartile range, 95];
P
<0.01). Two patients had recurrent premature ventricular contractions within 2 weeks after ablation, and no recurrences occurred in the remaining patients during a median follow-up of 13 months (range, 25). In the 7 patients with unsuccessful ablation, failure was because the ablation catheter could not be advanced to the SOO within the great cardiac vein (n=4), inadequate power delivery at the SOO (n=1), proximity to the phrenic nerve (n=1), or proximity of the SOO to a major coronary artery (n=1). Transcutaneous epicardial ablation was effective in 1 of 2 patients in whom it was attempted.

Conclusions—

Almost 15% of idiopathic ventricular arrhythmias have an epicardial origin. ECG characteristics help to differentiate epicardial arrhythmias from endocardial ventricular arrhythmias. The SOO of epicardial arrhythmias can be ablated from within the CVS in approximately 70% of patients.
Major Predictors of Long-Term Clinical Outcomes After Coronary Revascularization in Patients With Unprotected Left Main Coronary Disease
Authors: Min Sun-Yang , Park Duk-Woo , Yun Sung-Cheol , Kim Young-Hak , Lee Jong-Young , Kang Soo-Jin , Lee Seung-Whan , Lee Cheol Whan , Kim Jae-Joong , Park Seong-Wook , Park Seung-Jung
Published: April 2010

Background—

The clinical characteristics that identify high-risk subsets of patients with unprotected left main coronary artery disease undergoing percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) have not been well established.

Methods and Results—

Between January 2000 and June 2006, 2240 patients with unprotected left main coronary artery disease underwent PCI (n=1102) or CABG (n=1138). Twenty-six preprocedural parameters were evaluated by univariate and multivariate Cox regression analysis to identify independent predictors of all-cause mortality and target-vessel revascularization. Interaction tests were performed to compare heterogeneities of effects of preprocedural parameters depending on the revascularization methods. During follow-up (median of 3.1 years), 187 patients died (78 PCI and 109 CABG) and 149 patients had target-vessel revascularization (121 PCI and 28 CABG). EuroSCORE ≥6 was an independent predictor of death in both groups. Additional independent predictors were chronic renal failure and previous congestive heart failure in the PCI group and age ≥75 years, atrial fibrillation, right coronary artery disease, and left main distal bifurcation disease in the CABG group. Interaction analysis showed no heterogeneities of the effects of variables depending on the revascularization methods. Independent predictors of target-vessel revascularization were acute coronary syndrome and left main distal bifurcation disease in the PCI group and history of coronary intervention in the CABG group. The interaction between previous PCI and treatment remained after adjustment for all independent predictors of target-vessel revascularization (interaction
P
=0.0345).

Conclusions—

Several clinical characteristics were identified as important preprocedural predictors of long-term adverse outcomes after percutaneous or surgical revascularization in patients with unprotected left main coronary artery disease.
Impact of Introducer Sheath Coating on Endothelial Function in Humans After Transradial Coronary Procedures
Authors: Dawson Ellen A. , Rathore Sudhir , Cable N. Timothy , Wright D. Jay , Morris John L. , Green Daniel J.
Published: April 2010

Background—

The aim of this study was to compare the impact of transradial catheterization with hydrophilic-coated catheter sheaths versus uncoated sheaths on NO-mediated endothelial-dependent and -independent vasodilator function.

Methods and Results—

Thirty-five subjects undergoing transradial catheterization were recruited and assessed before and the day after catheterization. A subgroup was also assessed 3 to 4 months after catheterization. Subjects received hydrophilic-coated sheaths (n=15) or uncoated sheaths (n=20). Radial artery flow-mediated dilatation and endothelium- and NO-dependent arterial dilatation were assessed within the region of sheath placement. Glyceryl trinitrate endothelium-independent NO-mediated function was also assessed. The noncatheterized arm provided an internal control. Flow-mediated dilatation in the catheterized arm decreased from 10.3�3.8% to 5.3�3.3% and 8.1�2.4% to 5.2�3.7% in the coated and uncoated groups, respectively (
P
<0.01). These values returned toward baseline levels ≈3 months later (coated, 6.4�1.4%; uncoated, 9.4�4.1%;
P
<0.05) versus postprocedure. Glyceryl trinitrate decreased from 14.8�7.2% to 9.5�4.1% (
P
<0.05) in the coated group and from 12.2�4.6% to 7.5�4.2% (
P
<0.01) in the uncoated group. Values returned to baseline at ≈3 months (coated, 16.6�5.6%; uncoated, 12.1�3.9%;
P
<0.05). There was no difference in the magnitude of decrease in flow-mediated dilatation or glyceryl trinitrate between coated and uncoated groups. No changes in function occurred in the noncatheterized arm.

Conclusions—

Placement of a catheter sheath inside the radial artery disrupts vasodilator function, which recovers after 3 months. No differences were evident between hydrophilic-coated and uncoated sheaths.
Combined Mitral and Tricuspid Valve Repair in Rheumatic Valve Disease
Authors: Bernal José M. , Pontón Alejandro , Diaz Begoña , Llorca Javier , García Iván , Sarralde J. Aurelio , Gutiérrez-Morlote Jesús , Pérez-Negueruela Carolina , Revuelta José M.
Published: April 2010

Background—

We examined predictors of early and very long-term outcome after combined mitral and tricuspid valve repair for rheumatic disease.

Methods and Results—

Between 1974 and 2002, 153 consecutive patients (mean age, 46.0±13.2 years) underwent combined mitral and tricuspid valve repair for rheumatic disease. Mitral disease was predominantly stenosis (82.3%); 100% of patients had organic tricuspid valve disease, predominantly with regurgitation (53.6%) or some degree of tricuspid stenosis (46.4%). Mitral repair included commissurotomy in 132 patients (86.3%) associated with a flexible annuloplasty in 108. Tricuspid valve repair included flexible annuloplasty in 68 patients (44.4%) and suture annuloplasty in 20 patients (13.1%) combined with tricuspid commissurotomy in 62 patients (42.5%). Thirty-day mortality was 5.9%. Late mortality was 60.1%. The median follow-up was 15.8 years (interquartile range, 6 to 19 years). Follow-up was 97.9% complete. Age >65 years was the only predictor of late mortality. Kaplan-Meier survival probability was 74.4% at 10 years and 57.0% at 15 years. Sixty-three patients required valve reoperation (mitral valve, 59; tricuspid valve, 38). Predictors of valve reoperations were either mitral or tricuspid commissurotomy without associated prosthetic ring annuloplasty. At 20 years, Kaplan-Meier freedom from reoperation was 48.5±5.1%.

Conclusions—

Combined mitral and tricuspid valve repair in rheumatic disease showed satisfactory early results. Long-term results were poor because of high mortality and a high number of valve-related reoperations. The use of prosthetic ring annuloplasty was significantly associated with a reduced incidence of both mitral and tricuspid valve reoperations.
Cardioprotective and Antiapoptotic Effects of Heme Oxygenase-1 in the Failing Heart
Authors: Wang Guangwu , Hamid Tariq , Keith Rachel J. , Zhou Guihua , Partridge Charles R. , Xiang Xilin , Kingery Justin R. , Lewis Robert K. , Li Qianhong , Rokosh D. Gregg , Ford Rachael , Spinale Francis G. , Riggs Daniel W. , Srivastava Sanjay , Bhatnagar Aruni , Bolli Roberto , Prabhu Sumanth D.
Published: April 2010

Background—

Heme oxygenase-1 (HO-1) is an inducible stress-response protein that imparts antioxidant and antiapoptotic effects. However, its pathophysiological role in cardiac remodeling and chronic heart failure (HF) is unknown. We hypothesized that induction of HO-1 in HF alleviates pathological remodeling.

Methods and Results—

Adult male nontransgenic and myocyte-restricted HO-1 transgenic mice underwent either sham operation or coronary ligation to induce HF. Four weeks after ligation, nontransgenic HF mice exhibited postinfarction left ventricular (LV) remodeling and dysfunction, hypertrophy, fibrosis, oxidative stress, apoptosis, and reduced capillary density, associated with a 2-fold increase in HO-1 expression in noninfarcted myocardium. Compared with nontransgenic mice, HO-1 transgenic HF mice exhibited significantly (
P
<0.05) improved postinfarction survival (94% versus 57%) and less LV dilatation (end-diastolic volume, 46±8 versus 85±32 μL), mechanical dysfunction (ejection fraction, 65±9% versus 49±16%), hypertrophy (LV/tibia length 4.4±0.4 versus 5.2±0.6 mg/mm), interstitial fibrosis (11.2±3.1% versus 18.5±3.5%), and oxidative stress (3-fold reduction in tissue malondialdehyde). Moreover, myocyte-specific HO-1 overexpression in HF promoted tissue neovascularization and ameliorated myocardial p53 expression (2-fold reduction) and apoptosis. In isolated mitochondria, mitochondrial permeability transition was inhibited by HO-1 in a carbon monoxide (CO)–dependent manner and was recapitulated by the CO donor tricarbonylchloro(glycinato)ruthenium(II) (CORM-3). HO-1–derived CO also prevented H
2
O
2
-induced cardiomyocyte apoptosis and cell death. Finally, in vivo treatment with CORM-3 alleviated postinfarction LV remodeling, p53 expression, and apoptosis.

Conclusions—

HO-1 induction in the failing heart is an important cardioprotective adaptation that opposes pathological LV remodeling, and this effect is mediated, at least in part, by CO-dependent inhibition of mitochondrial permeability transition and apoptosis. Augmentation of HO-1 or its product, CO, may represent a novel therapeutic strategy for ameliorating HF.
Risk Factors for Venous Thromboembolism
Authors: Holst Anders G. , Jensen Gorm , Prescott Eva
Published: April 2010

Background—

Studies have suggested a link between risk factors for atherosclerotic disease and venous thromboembolism (VTE), but results are heterogeneous. We sought to identify risk factors for VTE with a focus on risk factors for atherosclerotic disease.

Methods and Results—

Data were taken from the Copenhagen City Heart Study, a prospective cohort study of a random, age-stratified sample of people living in a defined area in Copenhagen, Denmark, started in 1976 with follow-up until 2007. First VTE (deep vein thrombosis and pulmonary embolism) diagnosis was retrieved from electronic national registries from study baseline to 2007. Of 18 954 subjects (median follow-up, 19.5 years) representing 360 399 person-years of follow-up, 969 subjects experienced at least 1 VTE, corresponding to a crude incidence rate of 2.69 (95% confidence interval [CI], 2.52 to 2.86) per 1000 person-years. The variables found to be significantly associated with VTE in a multivariable model adjusted for age and calendar time were as follows: body mass index (hazard ratio [HR] for ≥35 versus <20=2.10 [95% CI, 1.39 to 3.16]); smoking (HR for ≥25 g tobacco per day versus never smoker=1.52 [95% CI, 1.15 to 2.01]); gender (HR for men versus women=1.24 [95% CI, 1.08 to 1.42]); household income (HR for medium versus low=0.82 [95% CI, 0.70 to 0.95]); and diastolic blood pressure (HR for >100 versus <80 mm Hg=1.34 [95% CI, 1.08 to 1.66]). Other cardiovascular risk factors including total/high-density lipoprotein/low-density lipoprotein cholesterol levels, triglyceride levels, and diabetes mellitus were not associated with VTE.

Conclusions—

Obesity and smoking were both found to be important risk factors for VTE whereas total/high-density lipoprotein/low-density lipoprotein cholesterol levels, triglyceride levels, and diabetes mellitus were not.
Lowering Midlife Levels of Systolic Blood Pressure as a Public Health Strategy to Reduce Late-Life Dementia
Authors: Launer Lenore J. , Hughes Timothy , Yu Binbing , Masaki Kamal , Petrovitch Helen , Ross G. Webster , White Lon R.
Published: April 2010

To estimate the potential benefits of lowering systolic blood pressure (SBP) toward preventing late-life dementia, we estimated the population-attributable risk of elevated SBP for dementia. Analyses are based on the cohort of 8006 Japanese American men (born 1900–1919) followed since 1965 as a part of the Honolulu Heart Program, continued as the Honolulu Asia Aging Study. Midlife cardiovascular risk factors and late-life brain function are well described. We estimated the population-attributable risk of dementia cases attributed to midlife SBP, grouped by the seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure criteria (<120, 120 to <140, and ≥140 mm Hg), taking into account treatment history, confounding factors, and competitive risk for death. The analysis is based on 7878 subjects, including 491 cases of dementia, with a mean interval of 25 years between measurement of blood pressure and dementia diagnosis. Compared with those with SBP <120 mm Hg, untreated, and <50 years of age at baseline, 17.7% (95% CI: 4.6% to 29.1%) of the cases were attributable to prehypertensive levels (SBP: 120 to <140 mm Hg) of SBP, translating into 11 excess cases per 1000. Among those who did not report taking antihypertensive medication in midlife, 27% (95% CI: 8.9% to 42.1%) of dementia cases can be attributed to systolic BP ≥120 mm Hg, translating into 17 excess cases per 1000. Although population-attributable risk estimates for population subgroups may differ by relative risk for dementia or prevalence of elevated levels of blood pressure, these data suggest that reducing midlife systolic BP is an effective prevention strategy to reduce risk for late-life dementia.
Filling Pressures and Collagen Metabolism in Hypertensive Patients With Heart Failure and Normal Ejection Fraction
Authors: González Arantxa , López Begoña , Querejeta Ramón , Zubillaga Elena , Echeverría Tomás , Díez Javier
Published: April 2010

This study was designed to evaluate the association between circulating biomarkers of collagen metabolism and elevated left-sided filling pressures (FPs), as assessed from elevated estimated pulmonary capillary wedge pressure (ePCWP), in hypertensive patients with heart failure with normal ejection fraction. Echocardiography was performed and ePCWP was calculated from the formula ePCWP=1.90+1.24(maximum early transmitral flow velocity in diastole:tissue Doppler early mitral annulus velocity). The biomarkers of collagen synthesis (carboxy-terminal propeptide of procollagen type I) and degradation (matrix metalloproteinase [MMP] 1 and tissue inhibitor of MMP-1 [TIMP-1]) were analyzed by ELISA methods. Seventy-eight patients with normal FPs (ePCWP ≤15 mm Hg) and 78 with elevated FPs (ePCWP >15 mm Hg) were included. Compared with controls, the levels of the 3 biomarkers were increased in the 2 groups of patients. The MMP-1:TIMP-1 ratio, an index of MMP-1 activity, was increased in patients with normal FPs and unchanged in patients with elevated FPs. Patients with elevated FPs exhibited higher TIMP-1 levels and a lower MMP-1:TIMP-1 ratio than patients with normal FPs. ePCWP was independently associated with TIMP-1 (
r
=0.349;
P
<0.001) and the MMP-1:TIMP-1 ratio (
r
=−0.240;
P
<0.01) in all of the patients. Receiver operating characteristic curves showed that a cutoff value of TIMP-1 of 1557 ng/mL provided 64% sensitivity and 67% specificity for predicting elevated FPs with a relative risk of 3.71 (95% CI: 1.91 to 7.22). These findings suggest that, in hypertensive patients with heart failure with normal ejection fraction and elevated FPs, collagen synthesis predominates over degradation because of a relative excess of TIMP-1. This imbalance can facilitate myocardial fibrosis, which, in turn, may contribute to the elevation of FPs in these patients.
The Phenomenology, Contextuality, and Existentiality of Emotional Trauma: Ethical Implications
Authors: Stolorow Robert D.
Published: April 2010

In this article, the author chronicles the emergence of two interrelated themes that crystallized in his investigations of the phenomenology of emotional trauma over the course of more than 19 years. One pertains to the context embeddedness of emotional trauma and the other to the claim that the possibility of emotional trauma is built into our existential constitution. The author finds a synthesis of these two themes—trauma’s contextuality and its existentiality—in the recognition of the bonds of deep emotional attunement we can form with one another in virtue of our common finitude. Grasping the relationality of finitude holds significant ethical implications.