bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of density of states on optical properties of GaSe thin film
Authors: Thamilselvan M. , Premnazeer K. , Mangalaraj D. , Narayandass Sa. K. , Yi Junsin
Published: February 2004

A systematic investigation on the effect of substrate temperature on the structure, optical absorption and density of states of vacuum evaporated gallium monoselenide (GaSe) thin films is reported. The X‐ray diffraction analysis shows an occurrence of amorphous to polycrystalline transformation in the films deposited at higher‐temperature substrates (573K). The compositional analysis is made with Auger Electron Spectroscopy (AES). The thickness of the film (175nm) is measured by a multiple beam interferometery. Optical characteristics of the GaSe sample have been analyzed using spectrophotometer in the photon energy range of 1.0 ‐ 4 eV. The absorption mechanism has been recognized and the allowed indirect as well as forbidden direct transitions have been found. As‐deposited films show two indirect and allowed transitions due to spin‐orbit splitting of the valence band, as reported here for the first time. Low field conduction have enabled us to determine the density of states in amorphous and poly‐GaSe films. The amorphous and polycrystalline GaSe thin films have localized states density values of N (EF) = 1.686 × 1017 cm‐3 eV‐1 and 1.257 × 1015 cm‐3 eV‐1 respectively. The experimental results are interpreted in terms of variations in the density of localized states due to progressive decrease of the unsaturated bonds during deposition. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Measurements of optical anisotropy of a calamitic lyotropic liquid crystal
Authors: Beica T. , Moldovan R. , Tintaru M. , Enache I. , Frunza S.
Published: February 2004

Optical birefringence measurements for a calamitic lyotropic liquid crystal containing sodium lauryl sulphate/decanol/water are presented. A value of the order of 10‐3 was obtained, much smaller than that of thermotropic liquid crystals. The order parameter temperature dependence is evaluated using an extrapolating method and taking into accounts the influence of the micelle shape. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Dielectric characteristics of Ce3+ doped Sr0.61Ba0.39Nb2O6 with Cole‐Cole plots technique
Authors: Şentürk E.
Published: February 2004

In this paper, we have investigated two‐relaxator mechanism and dielectric characteristics of Ce3+ doped Sr0.61Ba0.39Nb2O6 with dielectric spectroscopy measurements. The crystal undergoes a ferroelectric phase transition at 340 K. The temperature dependence of the real and imaginer part of the complex dielectric susceptibility in vicinity of ferroelectric‐paraelectric phase transition has been studied in the frequency region 0.1 kHz–10 MHz. The measurements of the dielectric constant of the real and imaginer parts show strongly frequency dependence. The investigations of the dielectric constant revealed a non‐Debye type dielectric relaxation for Ce+3 doped SBN61 by using Cole‐Cole plots. It reveals the coexistence of the two dielectric relaxators in vicinity of the phase transition. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Crystal structure analysis of 5‐amino‐7‐(pyrrolidin‐1‐yl)‐2,4,4‐trimethyl‐1,4‐dihydro‐1,6‐naphthyridine‐8‐carbonitrile
Authors: Selvanayagam S. , Rajakannan V. , Narasinga Rao S. , Shanmuga Sundara Raj S. , Fun H. K. , Raghukumar V. , Velmurugan D.
Published: February 2004

The title compound [CCDC 199359], C16H20N5 crystallized in Monoclinic system with the space group C2/c. The unit cell parameters are: a = 16.554(6), b = 12.145(4), c = 16.221(5)Å and β = 102.67(1)°. The molecular structure is stabilized by an intramolecular C‐H…N type hydrogen bond and the molecular packing by the intermolecular C‐H…N and N‐H…N type hydrogen bonds. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Electrocatalytic Oxidation of Methanol on a Nickel‐Porphyrin IX Complex Modified Glassy Carbon Electrode in Alkaline Medium
Authors: Golabi S. M. , Nozad A.
Published: February 2004

Electrocatalytic oxidation of methanol on a glassy carbon disc electrode modified with Ni(II)‐hematoporphyrin IX, complex and conditioned by potential recycling in a limited range (between 100 and 600 mV vs. SCE) in 0.10 M NaOH solution, abbreviated as NiOHPME(A), was studied by cyclic voltammetry in alkaline medium. The results were compared with those obtained for a NiO modified glassy carbon electrode, NiOME, prepared in similar conditions. The findings show that the NiOHP film at NiOHPME(A) behaves as an efficient electrocatalyst for the oxidation of methanol in alkaline medium via Ni(III) species with the cross‐exchange reaction occurring throughout the layer at a low concentration of methanol and for a thin film of modifier. A plausible mechanism was proposed for catalytic oxidation of methanol at NiOHP modified electrode. Moreover, the effects of various parameters such as the scan rate, methanol concentration, thickness of NiOHP film and the real surface area of modified electrode on the oxidation of methanol were investigated. Finally, it has been shown that the NiOHPME(A) has a long‐term stability toward the oxidation of methanol.
Self‐Assembling of Hybrid Prussian Blue Units in Cinder Matrix: Characterization and Electrocatalysis
Authors: Kumar Annamalai Senthil , Chen Pei‐Yan , Zen Jyh‐Myng
Published: February 2004

Industrial waste cinder (CFe*) has been utilized as a stable anchoring matrix for self‐assembling of Fe(CN)63− as hybrid Prussian blue units (PB, *Fe3+FeII(CN)6) on a screen‐printed carbon electrode (SPE) for efficient catalytic applications. The waste cinder was found to be a composite of calcium and iron silicates similar to glass matrix by X‐ray photoelectron spectroscopic (XPS) study. The hybrid PB formations were confirmed by both FT‐IR and electrochemical methods. Most importantly, the free iron (Fe*) ion bound to the non‐bridging oxygen terminals of the silicates was found to play a key role in the PB formation. The self‐assembled PB hybrid on the cinder‐modified screen‐printed electrodes (designated as PBCFe*‐SPE) improved linear detection range and sensitivity for H2O2 mediated oxidation than those obtained at a classical PB‐SPE in 0.1 M, pH 2 KCl/HCl base electrolyte at 0.0 V (vs. Ag/AgCl) by amperometric batch analysis.
Determination of Azidothymidine – an Antiproliferative and Virostatic Drug by Square‐Wave Voltammetry
Authors: Vacek Jan , Andrysík Zdeněk , Trnková Libuše , Kizek René
Published: February 2004

The 3′‐azido‐3′‐deoxythymidine (AZT, Zidovudine) is an antiproliferative and virostatic drug widely used in human immunodeficiency virus type 1 (HIV‐1) infection treatment. With respect to side effects of high doses and a short half‐life of AZT, a fast and simple detection method for this agent could be helpful. The aim of our study was to determine AZT levels in natural samples (urine, serum, whole blood, and cell cultures, such as the HaCaT line of keratinocytes) without their mineralization and/or purification, by means of electrochemical methods using hanging mercury drop electrode (HMDE). On this electrode, AZT undergoes irreversible reduction at the peak potential near Ep−1.1 V (vs. Ag/AgCl/3 M KCl). Reduction AZT signals were measured by cyclic voltammetry (CV), differential pulse voltammetry (DPV), square‐wave voltammetry (SWV), and constant current chronopotentiometric stripping analysis (CPSA). In phosphate buffer (pH 8) the SWV yielded the best AZT signal with the detection limit of 1 nM. The determination of AZT concentration in biological materials is affected by electroactive components, such as proteins and DNA. For monitoring the influence of these compounds, AZT reduction was performed in the presence of 10 μg/mL calf thymus ssDNA and/or 100 μg/mL bovine serum albumin. In these cases, the detection limit increased to 0.25 μM. Also studied was the AZT concentration in keratinocyte cells (HaCaT line) during cell cultivation. It has been shown that the SWV may be considered as a useful tool for the determination of AZT concentration in cell cultures, and for monitoring AZT pharmacokinetics.
Reference Electrodes Based on Solid Amalgams
Authors: Yosypchuk Bogdan , Novotný Ladislav
Published: February 2004

A reference saturated calomel electrode based on the non‐toxic silver solid amalgam (SCE‐AgSA) as a substitute for liquid mercury is described. Long‐term as well as short‐term tests made during a period of one year confirmed the SCE‐AgSA potential to be equal to that of SCE within the limits of ±1 mV (the difference ΔESCE‐AgSA=+1.08±0.24 mV (vs. SCE); SD=0.87; N=51). The voltammograms of four selected metal ions registered vs. SCE‐AgSA and vs. SCE could practically overlap each other. None of the mentioned electrodes were polarized to a significant degree even if the electric current applied reached 2 mA. On the basis of the obtained results the SCE‐AgSA could be considered as equivalent substitute for SCE. Owing to practically identical electrode potential of both types of the mentioned electrodes the results obtained using SCE‐AgSA are completely comparable to those measured vs. SCE, without any correction of peak potentials.
Electrochemical Detection of Trace Concentrations of Cadmium and Lead with a Boron‐Doped Diamond Electrode: Effect of KCl and KNO3 Electrolytes, Interferences and Measurement in River Water
Authors: Babyak Carol , Smart Ronald B.
Published: February 2004

Parts‐per‐billion levels of cadmium and lead were detected using square‐wave anodic stripping voltammetry with a boron‐doped diamond electrode. Calibration plots (10‐minute deposition time) in KCl and KNO3 were non‐linear at low concentrations (1–5 ppb) due to the deposition mechanism of these metals. The preferred electrolyte for cadmium was KCl, while lead could be measured in either electrolyte. The lowest concentrations included in the linear portion of the calibration plot (5 minute deposition time) for cadmium were 10 ppb and 50 ppb in KCl and KNO3, respectively, and 10 ppb for lead in KNO3. The presence of either lead or copper suppressed the cadmium stripping peak, but the lead stripping peak was unaffected by cadmium, and enhanced by the addition of copper. A river water sample was analyzed for cadmium and lead, and the cadmium results were confirmed using ICP‐AES spectrometry. It was determined electrochemically that a fraction of lead in the river sample was bound by complexing material in the sample.
Determination of Reserpine in Urine by Capillary Electrophoresis with Electrochemiluminescence Detection
Authors: Cao Weidong , Yang Xiurong , Wang Erkang
Published: February 2004

A fast and sensitive approach to detect reserpine in urine using micellar electrokinetic capillary chromatography with electrochemiluminescence (ECL) of Ru(bpy)32+ detection is described. Using a 25 μm i.d. capillary as separation column, the ECL detector was coupled to the capillary in the absence of an electric field decoupler. Field‐amplified injection was used to minimize the effect of ionic strength in the sample and to achieve high sensitivity. In this way, the sample was analyzed directly without any pretreatment. The method was validated for reserpine in the urine over the range of 1×10−6−1×10−4 mol/L with a correlation coefficient of 0.996. The RSD for reserpine at a level of 5 μmol/L was 4.3%. The LOD (S/N=3) was estimated to be 7.0×10−8 mol/L. The average recoveries for 10 μmol/L reserpine spiked in human urine were 94%.
Flow Injection Amperometric Detection at Enzyme‐Modified Gold Nanoelectrodes
Authors: Delvaux Marc , Demoustier‐Champagne Sophie , Walcarius Alain
Published: February 2004

Gold nanotubular electrode ensembles were prepared by using electroless deposition of the metal within the pores of polycarbonate particle track‐etched membranes. Glucose oxidase (Gox), used as a model enzyme, has been immobilized onto preformed self‐assembled monolayers (mercaptoethylamine or mercaptopropionic acid) on electroless gold via cross‐linking with glutaraldehyde or covalent attachment by carbodiimide coupling. Flow‐injection analysis systems in flow‐through or wall‐jet configurations using these Gox‐modified nanoelectrodes are described. The influence of different experimental parameters (i.e., applied potential, flow rate, interferents…︁) on the analytical response of the sensor to glucose has been evaluated. Under optimized conditions, very reproducible results (standard deviations <4%, n=38) were obtained, linear calibration was achieved in the 2×10−4 M to 3×10−2 M concentration range and the detection limit was 2×10−4 M. Moreover, no significant interferences from species like ascorbic and uric acids were observed at a potential of +0.9 V.
Electroanalytical Characteristics of Amisulpride and Voltammetric Determination of the Drug in Pharmaceuticals and Biological Media
Authors: Özkan Sibel A. , Uslu Bengi , Sentürk Zühre
Published: February 2004

The electrochemical oxidation of antipsychotic drug amisulpride (AMS) has been studied in pH range 1.8–11.0 at a stationary glassy carbon electrode by cyclic, differential pulse and square‐wave voltammetry. Two oxidation processes were produced in different supporting electrolyte media. Both of the oxidation processes were irreversible and exhibited diffusion controlled. For analytical purposes, very resolved voltammetric peaks were obtained using differential pulse and square‐wave modes. The linear response was obtained in the range of 4×10−6 to 6×10−4 M for the first and second oxidation steps in Britton‐Robinson buffer at pH 7.0 and pH 3.0 (20% methanol v/v), respectively, using both techniques. These methods were used for the determination of AMS in tablets. The first oxidation process was chosen as indicative of the analysis of AMS in biological media. The methods were successfully applied to spiked human serum, urine and simulated gastric fluid samples.
Effect of Carbon Dioxide and Ammonia on Polymer Electrolyte Membrane Fuel Cell Stack Performance
Authors: Rajalakshmi N. , Jayanth T.T. , Dhathathreyan K.S.
Published: February 2004

Proton exchange membrane fuel cell (PEMFC) performance degrades when impurities are present in the anode fuel gas, referred to as catalyst poisoning. This paper investigates the effect of carbon dioxide and ammonia as impurities in the anode gas of the PEMFC, and found that the presence of CO2decreases the performance of the fuel cell by up to 10%. The performance loss depends on the CO2concentration and the exposure time. The voltage loss is recoverable on passing pure hydrogen gas, indicating that a permanent poisoning of the catalyst layer has not taken place. Exposure of the fuel cell to ammonia beyond 20 ppm, even for a short duration, causes permanent PEMFC failure, probably due to the deterioration of the membrane.
Analysis of Optimal Heat Transfer in a PEM Fuel Cell Cooling Plate
Authors: Chen F.C. , Gao Z. , Loutfy R.O. , Hecht M.
Published: February 2004

An analysis of three‐dimensional computational fluid dynamics (CFD) is conducted to investigate the coupled cooling process involved in fluid flow and heat transfer between the solid plate and the coolant flow for optimization of the cooling design of a fuel cell stack. A conception of IUT (Index of Uniform Temperature) across the entire area is presented to evaluate the degree of uniform temperature profile across the cooling plates. Six cooling modes, including three serpentine‐type modes and another three parallel‐type modes, are presented and analyzed for optimization of the cooling mode of fuel cells. The prediction finds that the cooling effect of serpentine‐type cooling modes could be better than that of parallel‐type cooling modes.
First Steps Towards Fuel Cells Testing Harmonisation: Procedures and Parameters for Single Cell Performance Evaluation
Authors: Lunghi P. , Ubertini S.
Published: February 2004

The great interest in Fuel Cell Systems, combined with the innovation of the device itself, has led to a huge developmental effort to make the steps necessary for future FC plant commissioning.

The clearest and most effective way to evaluate the performance of a fuel cell is to measure it directly and, since few fuel cell test rigs are available at the moment, standard experimental procedures have not been realized so far.

Our research group is currently performing single cell testing at the University of Perugia fuel cell laboratory and particular emphasis has been put on the definition of procedures and the testing of parameterisation. The work team strongly believes that this is the key to effective system testing and reliable performance evaluation.

In this work, the test parameterisation developed by the team, and the resulting advanced control procedure used for a single MCFC experimental characterization are presented. Efforts have been dedicated to obtain some relevant non‐dimensional parameters to allow an easy understanding of the results and quick comparisons with other tests under different operating conditions, or with results obtained on different cells eventually tested in different laboratories. The authors strongly emphasise this topic to avoid the data that developers and research institutions collect being of no practical use due to a lack of shared rules.
Design of a Tubular Ceramic Membrane for Gas Separation in a PEMFC System
Authors: Kamarudin S.K. , Daud W.R.W. , Mohammad A.W. , Som A.Md. , Takriff M.S.
Published: February 2004

The objective of this study is to introduce a shortcut in the method of design for a tubular ceramic membrane (TCM) for gas separation. Generally, it explains the permeation of the multi component gas using cross flow models in a porous membrane and the surface area of the membrane required. The novel aspect of this method is that the expression for the length of the membrane is simplified to a number unit (NTU) and a height of transfer unit (HTU). The HTU term for porous membranes is characterised by the physical properties of the membrane; the feed flow rate, nF, membrane thickness, lM, feed pressure, PF, K the permeability of gas and the diameter of the membrane, DM. The integral for NTU of a porous membrane is the solution for the local permeate along the length of the membrane. It is found that, NTU mainly depends on the rejection stream, xR,, along the membrane and it describes the relative degree of separation. The Proton Electrolyte Membrane Fuel Cell (PEMFC) system is taken as the case study. CO is the main culprit in reducing the performance of the PEMFC and will act as a catalyst poison for the fuel cell anode at a concentration as low as 100 ppm. Thus, the reformate, from primary reforming, contains a significant amount of CO and must be purified. The effect of some important parameters such as temperature, pressure and the thickness of membrane to the degree of separation are presented in this paper. From the results, it can be seen that the system could reduce the CO concentration from 2000 – 500 ppm. Basically the TCM will operate, in series, with a pressure swing adsorber in order to further reduce the concentration of CO to less than 10 ppm before entering the fuel cell stack. However, this paper only focuses on the design of the TCM. Besides this, it is observed that the purity of the hydrogen increased from 72.8 – 96% (at θ = 0.5) after the membrane.
Thermodynamics of Hydrogen Generation from Methane for Domestic Polymer Electrolyte Fuel Cell Systems
Authors: Barz D.P.J. , Trägner U.K. , Schmidt V.M. , Koschowitz M.
Published: February 2004

Low temperature fuel cells such as the Polymer Electrolyte Fuel Cell (PEFC) are preferably used for domestic applications because of their moderate operating conditions. Using the existing distribution system, natural gas is used as a source for a hydrogen rich gas to power this fuel cell type. The high requirements on the fuel gas quality as well as high conversion efficiencies for the small local gas processing units are critical aspects in the evaluation of decentralized fuel cell systems. In the present paper, three typical gas processing methods are evaluated for the supply of a hydrogen rich gas for PEFCs: steam reforming, partial oxidation, and autothermic conversion. All three processes are studied in detail by varying the relevant process parameters: temperature, pressure, steam to fuel ratio, and oxygen to fuel ratio. The results are graphically displayed in numerous nomograms. With the help of these graphs, regions of stable operation and the sensitivity to the operational parameters are discussed. For all three gas processing methods, the graphs generated display methane conversion, the hydrogen yield, and the yields of unwanted components, i.e., carbon monoxide and solid carbon. Although only steady‐state operating conditions were simulated, critical modes of operation, which might occur during start‐up or transient operation can easily be identified. For instance, operating conditions where soot is generated have to be avoided under all circumstances. All simulations were done with the Gibb's reactor model of a commercial simulation program. The Gibb's reactor model was found to be a suitable tool, since the simulated results compared well with reported literature data. According to the simulation results, the methane‐steam‐reforming process appears to be favorable for application to PEFCs. Methane conversion and hydrogen yields are highest for this process while the yield of CO is relatively low.
Electrochemical Reduction of Oxygen on Carbon Supported Pt and Pt/Ru Fuel Cell Electrodes in Alkaline Solutions
Authors: Yu E.H. , Scott K. , Reeve R.W.
Published: February 2004

A study of O2 reduction in 1 M NaOH solution at gas diffusion electrodes made from carbon supported Pt and Pt/Ru catalysts is reported. Two Tafel regions were observed for both the Pt and Pt/Ru electrodes. Although the same mechanism was suggested for oxygen reduction on both Pt and Pt/Ru catalysts, the O2 reduction activity was lower on Ru. Electrochemical Impedance Spectroscopy (EIS) analysis was carried out at different potentials and showed the significant contribution of diffusion on the reaction process and kinetics. The effect of methanol on O2 reduction was investigated in solutions containing various concentrations of methanol. The electrode performance deteriorated with increasing methanol concentration because of a mixed cathode potential. The methanol tolerance, i. e., the methanol concentration which polarises the O2 reduction reaction for O2 reduction, at the Pt/C electrode with a Pt loading of 1.2 mg cm–2 is 0.2 M methanol in 1 M NaOH.
Analysis of Direct Methanol Fuel Cell (DMFC)‐Performance via FTIR Spectroscopy of Cathode Exhaust
Authors: Meier F. , Denz S. , Weller A. , Eigenberger G.
Published: February 2004

Water and methanol flux through Nafion™ and polyaryl‐blend membranes prepared at ICVT were studied under DMFC operation. The water, methanol, and CO2 content in the cathode exhaust were measured by FTIR spectroscopy. Both the water and methanol flux turned out to be strongly dependent on the operating temperature and thus on membrane swelling. Apart from this, water flux through the membrane is primarily affected by the gas volume flux on the cathode side. A coupling between water flux and methanol flux was observed, which leads to the conclusion that methanol is transported both by diffusion and by convection caused by the superimposed water flux. Polyaryl‐blend membranes showed a reduced diffusive methanol transport when compared to Nafion™ due to their different internal microstructure. The impact of methanol cross‐over on cathode losses at high current density needs further clarification with respect to the prevailing mechanism of methanol oxidation at the cathode.
−160C/A polymorphism in the E‐cadherin gene promoter and risk of hereditary, familial and sporadic prostate cancer
Authors: Jonsson Björn‐Anders , Adami Hans‐Olov , Hägglund Maria , Bergh Anders , Göransson Ingela , Stattin Pär , Wiklund Fredrik , Grönberg Henrik
Published: February 2004

The E‐cadherin (CDH1) gene has been associated with prostate carcinogenesis. The C/A polymorphism −160 base pairs relative to the transcription start site has been shown to decrease gene transcription. We analyzed the association between this polymorphism and the risk of sporadic, familial (2 close relatives) and hereditary (3 or more close relatives) prostate cancer. We combined data from 3 population‐based epidemiologic studies in Sweden encompassing altogether 1,036 prostate cancer cases and 669 controls that were genotyped for the short nucleotide polymorphism. Odds ratios with 95% confidence intervals were estimated through unconditional logistic regression. We found no significant association between the A‐allele and sporadic (OR = 1.0; 95% CI = 0.8–1.2) or familial (OR = 1.4; 95% CI = 0.9–2.2) prostate cancer. In contrast, risk of hereditary cancer was increased among heterozygote CA carriers (OR = 1.7; 95% CI = 1.0–2.7) and particularly among homozygote AA carriers (OR = 2.6; 95% CI = 1.4–4.9). Our data indicate that the −160 single nucleotide polymorphism in CDH1 is a low‐penetrant prostate cancer susceptibility gene that might explain a proportion of familial and notably hereditary prostate cancer. © 2004 Wiley‐Liss, Inc.
Genetic downregulation of pregnancy‐associated plasma protein‐A (PAPP‐A) by bikunin reduces IGF‐I‐dependent Akt and ERK1/2 activation and subsequently reduces ovarian cancer cell growth, invasion and metastasis
Authors: Tanaka Yoshiko , Kobayashi Hiroshi , Suzuki Mika , Hirashima Yasuyuki , Kanayama Naohiro , Terao Toshihiko
Published: February 2004

A Kunitz‐type protease inhibitor, bikunin, downregulates expression of uPA and its receptor uPAR at the mRNA and protein levels in several types of tumor cells. Our recent work showed that, using a cDNA microarray analysis, pregnancy‐associated plasma protein‐A (PAPP‐A) is a candidate bikunin target gene. To clarify how reduced levels of PAPP‐A may confer repressed invasiveness, we transfected human ovarian cancer cell line HRA with antisense (AS)‐PAPP‐A cDNA and compared the properties of the transfected cells to those of parental HRA cells. Here, we show that regulation of uPA mRNA and protein by IGF‐I depends on the PI3K and MAPK signaling pathways and phosphorylation of Akt and ERK1/2 is required for IGF‐I‐mediated cell invasion; that IGFBP‐4 protease in HRA cells is identified as PAPP‐A; that reduced PAPP‐A expression is associated with the upregulation of IGFBP‐4 expression; that higher intact IGFBP‐4 levels were associated with low invasive potential and growth rate in AS‐PAPP‐A cells in response to IGF‐I; that IGF‐I stimulates Akt and ERK1/2 activation of both the control and antisense cells, but the relative potency and efficacy of IGF‐I were lower in the antisense cells compared to the control; and that genetic downregulation of PAPP‐A reduces the proliferation, invasion and metastasis of HRA cells. In conclusion, our data identify a novel role for PAPP‐A as a bikunin target gene. IGF‐I‐induced IGFBP‐4 proteolysis by PAPP‐A may enhance cell growth and invasion through IGF‐I‐dependent Akt and ERK1/2 activation and subsequently upregulation of uPA. © 2004 Wiley‐Liss, Inc.
Tumor necrosis factor‐α augmented tumor response in B16BL6 melanoma‐bearing mice treated with stealth liposomal doxorubicin (Doxil®) correlates with altered Doxil® pharmacokinetics
Authors: Brouckaert Peter , Takahashi Nozomi , van Tiel Sandra T. , Hostens Jeroen , Eggermont Alexander M.M. , Seynhaeve Ann L.B. , Fiers Walter , ten Hagen Timo L.M.
Published: February 2004

The application of tumor necrosis factor‐α (TNF) for the treatment of solid tumors is limited by its severe, life‐threatening, toxicity. Therefore, only low dosages of this cytokine can be applied systemically, which results in poor tumor response. It has been demonstrated previously that administration of high‐dose TNF in a so‐called isolated perfusion system markedly improved tumor response when combined with chemotherapy. It appeared that TNF had a major impact specifically on the tumor‐associated vasculature. At these high concentrations, endothelial cell death is induced by TNF, resulting in complete collapse of the tumor vascular bed. Strikingly, this effect alone is not enough to induce a tumor response, but addition of a chemotherapeutic drug is mandatory to obtain an anti‐tumor effect. We showed that TNF has no anti‐tumor effect by itself but augmented drug accumulation mainly in the tumor, most likely by enhancing vascular leakage. It seems that enhanced vascular leakage, but not endothelial cell death, explains the interaction between TNF and the co‐administered drug. We hypothesized that in a low‐dose setting TNF could induce tumor accumulation of chemotherapeutic drugs and consequently improve tumor response. We demonstrate that free TNF has a strong effect on the pharmacokinetics of co‐administered Doxil® in B16BL6 melanoma‐bearing mice, resulting in strongly augmented drug accumulation in the tumor and improved tumor response. Co‐injection of Stealth® liposomal TNF with Doxil® resulted in comparable or less pronounced tumor responses as compared to free TNF. These results imply that systemic application of clinically tolerable doses of TNF may improve drug distribution and tumor response and could be useful in a number of anti‐cancer therapies. © 2004 Wiley‐Liss, Inc.
Preclinical evaluation of the nonsteroidal anti‐inflammatory agent celecoxib on malignant mesothelioma chemoprevention
Authors: Catalano Alfonso , Graciotti Laura , Rinaldi Luciana , Raffaelli Giorgia , Rodilossi Sabrina , Betta Piergiacomo , Gianni Walter , Amoroso Salvatore , Procopio Antonio
Published: February 2004

Malignant mesothelioma (MM) remains the most lethal pleural, peritoneal and pericardial cancer. Here, we characterize the effects of nonsteroidal anti‐inflammatory agents (NSAIDs) on in vitro and in vivo experimental MM models. Unlike primary normal mesothelial cells, the selective cyclooxygenase (COX)‐2 inhibitor celecoxib reduced the in vitro proliferation of several MM cells derived from previously untreated MM patients. Moreover, celecoxib significantly inhibited MM cell colony formation in soft agarose (63–78% at 5 × 10−5 M; p ≤ 0.05) and it elicited remarkable antitumor activity, leading to long‐term survival in >37% of nude mice bearing intraperitoneal MM. Celecoxib was more efficient in inhibiting MM cell growth than acetylsalicylic acid (10−6 M‐10−2 M), indometacin (10−6 M‐10−2 M) and the COX‐2 inhibitor NS‐398 (10−6 M‐10−4 M). Efficacy of these different compounds was not related to the amount of COX‐2 protein levels present on MM cells. Celecoxib, in a dose‐ and time‐dependent manner, induced MM cell apoptosis, which involved decreased Akt phosphorylation, loss of Bcl‐2 and Survivin protein expression and caspase‐3 activation. Furthermore, vascular endothelial growth factor (VEGF), an MM autocrine growth factor and Akt inducer, rescued celecoxib‐induced apoptosis and Akt dephosphorylation. When the VEGF receptor (KDR/Flk‐1) inhibitor, SU‐1498, was used in combination with celecoxib, IC50 of celecoxib in vitro was reduced up to 65%. These data demonstrate that celecoxib may have antitumor properties in MM and provide a rationale for the therapeutic use of celecoxib in combination with a selective VEGF inhibitor. © 2004 Wiley‐Liss, Inc.
Loss of PKR activity in chronic lymphocytic leukemia
Authors: Hii Su Ing , Hardy Lani , Crough Tania , Payne Elizabeth J. , Grimmett Karen , Gill Devinder , McMillan Nigel A.J.
Published: February 2004

There are a number of observations that suggest the dsRNA‐activated protein kinase, PKR, may play an active role in formation and maintenance of leukemia, including nonrandom chromosomal deletions in acute leukemia as well as truncations and deletions of the PKR gene in some leukemia cell lines. However, there is little direct evidence from patient material that this is so. Here we show that full‐length PKR is present but not active in 21 of 28 patient samples from B‐cell chronic lymphocytic leukemia (B‐CLL). PKR from these patients was unable to auto‐activate or phosphorylate substrates but was able to bind dsRNA. Furthermore, the lack of PKR activation was not due to differing levels of the PKR activator, PACT nor of the PKR inhibitor, p58IPK. We compared PKR status with clinical parameters and disease staging. No differences were found between the 2 groups in terms of staging (modified Rai or Binet), age, CD38 status, p53 status, 11q23 deletion status or CEP12 deletion status. However, there was a significant correlation between deletion in 13q14.3 and lack of PKR activity. We show that B‐CLL cells appear to contain a soluble inhibitor of PKR, as lysates from cells lacking PKR activity were able to inhibit exogenous PKR in mixing experiments. Finally, we show suppression of PKR activity was still present following ultrafilitration through a 10,000 Da cutoff filter but was lost upon extraction with phenol/chloroform or by high salt washing. This data suggests loss of PKR activity may contribute to the formation and/or maintenance of CLL. © 2004 Wiley‐Liss, Inc.
No ING1 mutations in human brain tumours but reduced expression in high malignancy grades of astrocytoma
Authors: Tallen Gesche , Kaiser Ines , Krabbe Sonja , Lass Ulrike , Hartmann Christian , Henze Günter , Riabowol Karl , von Deimling Andreas
Published: February 2004

The ING1 family of proteins has been shown to have regulatory functions in oncogenesis, apoptosis, DNA repair and cell cycle regulation. Here we present the first report on LOH analysis of the ING1 locus, mutation analysis of the complete coding sequence including intron‐exon boundaries and expression analysis of the different ING1 splice products and protein isoforms in primary brain tumours. No somatic ING1 mutations were detected. Semi‐quantitative analysis revealed higher levels of p33ING1b RNA in benign than in malignant lesions. This correlation was significant in a subset of 37 astrocytic tumours WHO grades I to IV. ING1 protein isoforms p47ING1a, p33ING1b and p24ING1c were found to be expressed variably in this series. Our findings support a regulatory contribution of ING1 to the development or progression of brain tumours. © 2004 Wiley‐Liss, Inc.
Amplification of chromosome 1 sequences in lipomatous tumors and other sarcomas
Authors: Nilsson Malin , Meza‐Zepeda Leonardo A. , Mertens Fredrik , Forus Anne , Myklebost Ola , Mandahl Nils
Published: February 2004

Amplifications and gains involving 1q are common abnormalities in solid tumors. Recently, an amplicon originating from 1q21–23, containing the candidate oncogenesCOAS1,COAS2andCOAS3(Chromosome One Amplified Sequence) was identified. The presence, distribution and copy number level of extraCOASsequences were investigated in 48 bone and soft tissue tumor (BSTT) samples using metaphase FISH analysis. Amplification was seen in 27/48 (56%) samples. With few exceptions, all 3 genes were involved, but on averageCOAS2exhibited higher copy numbers. The presence of extraCOASsignals, irrespective of copy numbers, was found at similar frequencies in different histologic tumor subtypes. However, medium or high level amplification was common in lipomatous tumors but rare in other, nonlipomatous tumors (9/21vs. 2/27 samples). The most common localization of extraCOASsignals in lipomatous tumors was in supernumerary ring and giant marker chromosomes. Among nonlipomatous tumors, the distribution of extraCOASgenes was more disperse, being located in various unidentified chromosomal structures, including double minutes, and only rarely in ring chromosomes. BecauseMDM2is known to be amplified frequently in BSTTs, and in particular in atypical lipomatous tumors, cases with extra copies ofCOASwere studied also with anMDM2probe. Twelve out of 18 lipomatous tumors had extra copies of bothCOASandMDM2, and the 2 genes were found to be coamplified and interspersed exclusively in ring and giant marker chromosomes. Also 12 out of 18 nonlipomatous tumors exhibited simultaneous gain ofCOASandMDM2, but colocalization in the same chromosome was less frequent. The role of the frequent coamplification ofCOAS, or some other yet unknown gene in the 1q21–23 region, andMDM2remains to be elucidated. © 2004 Wiley‐Liss, Inc.
Cervical cancer as a priority for prevention in different world regions: An evaluation using years of life lost
Authors: Yang Binh H. , Bray Freddie I. , Parkin D. Maxwell , Sellors John W. , Zhang Zuo‐Feng
Published: February 2004

The relative importance of cancer of the cervix among several important causes of mortality (from cancer and other diseases) has been evaluated by estimating the years of life lost (YLL) by young and middle‐aged women (25–64 years old) in different regions of the world. The life years were weighted to reflect their importance to the individual and to society. On a global basis, cancer of the cervix is responsible for about 2% of the total (weighted) YLL, fewer than for other causes of mortality in this age group. However, it is the most important cause of YLL in Latin America and the Caribbean. It also makes the largest contribution to YLL from cancer in the populous regions of SubSaharan Africa and South‐Central Asia where the actual risk of loss of life from this cause is higher, although overshadowed by noncancer deaths (from AIDS, TB and maternal conditions). The overall picture is not very sensitive to the age weighting function used. The fact that most of the loss of life is preventable, and that simple technologies have been developed that make this practicable, means that cervical cancer has an even higher profile from the perspective of resource allocation in low income settings. © 2004 Wiley‐Liss, Inc.
CD1d is expressed on B‐chronic lymphocytic leukemia cells and mediates α‐galactosylceramide presentation to natural killer T lymphocytes
Authors: Fais Franco , Morabito Fortunato , Stelitano Caterina , Callea Vincenzo , Zanardi Sabrina , Scudeletti Marco , Varese Paola , Ciccone Ermanno , Grossi Carlo Enrico
Published: February 2004

Generation of immune responses against B cell chronic lymphocytic leukemia (B‐CLL) has been the aim of several studies that have demonstrated a poor antigen presenting ability of B‐CLL cells and an inconsistent emergence of T cells capable of killing efficiently the leukemic cells. CD1d is a restriction element structurally related to the major histocompatibility complex (MHC) and capable of presenting lipid antigens to CD1d‐restricted T cells (also defined as natural killer‐T [NKT] cells). The synthetic lipid α‐galactosylceramide (α‐GalCer) has been characterized as a potent stimulator of CD1d‐restricted T cells. We have investigated the expression of CD1d on B‐CLL cells. CD1d was detected by flow cytometric analyses on leukemic cells of all B‐CLL cases studied (n = 38) and was expressed at higher density on cells carrying unmutated immunoglobulin variable region (IgV) genes. In addition, CD1d on B‐CLL cells mediated the presentation of α‐GalCer to CD1d‐restricted T cells, which in turn induced B‐CLL cell death. At variance with another study (Metelitsa et al., Leukemia 2003;17:1068–77), no correlation between expression levels of CD1d and susceptibility to NKT cell lysis was observed. Proliferation and production of interferon‐γ (IFN‐γ) and tumor necrosis factor‐α (TNF‐α) by CD1d‐restricted T cells, in the presence of B‐CLL cells loaded with α‐GalCer, were also observed. Our study demonstrates that B‐CLL cells express a monomorphic restriction element that is functionally capable of antigen presentation and can be useful to design novel B‐CLL immunotherapies. © 2004 Wiley‐Liss, Inc.
Initial results from a randomized trial of cervical visual screening in rural south India
Authors: Sankaranarayanan Rengaswamy , Rajkumar Rajamanickam , Theresa Rajapandian , Esmy Pulikattil Okkaru , Mahe Cedric , Bagyalakshmi Karur R. , Thara Somanathan , Frappart Lucien , Lucas Eric , Muwonge Richard , Shanthakumari S. , Jeevan D. , Subbarao T.M. , Parkin Donald Maxwell , Cherian Jacob
Published: February 2004

The impact of a single round of screening of visual inspection with acetic acid (VIA) on cervical cancer incidence and mortality was investigated in a cluster randomized trial in south India. Women 30–59 years of age in 113 clusters in Dindigul District were randomized to VIA screening (57 clusters, 48,225 women) by nurses and to a control group (56 clusters, 30,167 women). 30,577 eligible women were screened between May 2000 and April 2003; 2,939 (9.6%) screen‐positive women were investigated with colposcopy by nurses and 2,777 (9.1%) women had biopsy. CIN 1 was diagnosed in 1,778 women, CIN 2‐3 lesions were found in 222, and there were 69 screen detected invasive cervical cancers. The detection rates of lesions per 1,000 screened women were 58.2 for CIN 1, 7.3 for CIN 2‐3, and 2.3 for invasive cancer. The detection rate of high‐grade lesions in our study was 2–3‐fold higher than those observed in repeatedly screened populations in developed countries. 71% of women with CIN 1 and 80% of those with CIN 2‐3 lesions accepted cryotherapy provided by nurses and surgical treatment by mid‐level clinicians. Overall, 97 and 34 incident cervical cancer cases were observed in the intervention and control arms, respectively. The intervention arm accrued 124,144 person years and the control arm accrued 90,172 during the study period. The age standardized cervical cancer incidence rates were 92.4/100,000 person‐years in the intervention and 43.1/100,000 in the control arms. In the screened arm, 35.0% of cases were in Stage I as opposed to none in the control arm. The preliminary findings from our study indicate that not only is a VIA‐based screening programme feasible, safe and acceptable to a population in rural settings, it also results in early detection of cervical neoplasia. © 2004 Wiley‐Liss, Inc.
Analysis of the natural killer mediated immune response in metastatic renal cell carcinoma patients
Authors: Gati Asma , Da Rocha Sylvie , Guerra Nadia , Escudier Bernard , Moretta Alessandro , Chouaib Salem , Angevin Eric , Caignard Anne
Published: February 2004

Metastatic renal cell carcinomas (MRCC) are considered as immunogeneic tumors on the basis of the clinical responses observed in patients treated by IL‐2. However, renal cell carcinoma patients are also characterized by alterations of the immune response that may compromise the immunotherapeutic approaches. In our study, we have studied the phenotype and the functional capacities of peripheral NK cells in a panel of neprectomized metastatic renal cell carcinoma patients. NK cells were harvested by negative immunoselection from fresh peripheral blood samples. In most of MRCC patients analysed (23/28), the expression of NCR (NKp46 and NKp30) was similar to that of donors. Lytic capacities by activated immunoselected NK cells from MRCC patients assessed against K562 and 3 renal tumor cell lines were in the range of that observed in NK cells from normal donors. HLA‐I− renal tumor cells UOK23 were killed with a good efficiency, whereas HLA‐I renal tumor cells were more resistant. Although LFA‐1/ICAM‐1 interaction potentiates RCC cell lysis, HLA‐I/NKR interaction clearly decreased RCC cell susceptibility to NK cells. In addition, proliferation of NK cells from MRCC patients in response to cytokines was altered. © 2004 Wiley‐Liss, Inc.
Poly(ADP‐ribose) polymerase‐1, a novel partner of progesterone receptors in endometrial cancer and its precursors
Authors: Ghabreau Lina , Roux Jean Paul , Frappart Pierre‐Olivier , Mathevet Patrice , Patricot Louis Marc , Mokni Moncef , Korbi Sadok , Wang Zhao‐Qi , Tong Wei‐Min , Frappart Lucien
Published: February 2004

Endometrial carcinomas are the most common malignancy of the female genital tract. Although the downregulation of the progesterone receptor (PR) in the progression of endometrioid carcinomas (ECs) has been well documented, the mechanism of PR alteration in endometrioid carcinogenesis is poorly understood. Recently, biochemical studies have shown that the DNA strand break‐sensing molecule poly(ADP‐ribose) polymerase (PARP‐1) was associated with the DNA binding domain of PR. In our present study, we show that in normal endometrial epithelium, the expression level of PARP‐1 protein is high in the proliferative phase but markedly decreases during the secretory phase. Interestingly, PARP‐1 expression gradually increases in nonatypical and atypical endometrial hyperplasia, reaching its highest level in grade I, and decreases significantly toward grade III ECs. Notably, PARP‐1 and PR expressions, in each stage, are positively correlated (p < 0.0001), with the exception of nonendometrioid carcinomas. Thus, these data suggest that PARP‐1 is substantially involved in the regulation of progesterone action in the development of ECs. © 2004 Wiley‐Liss, Inc.
Elevated hTERT mRNA levels: A potential determinant of bronchial squamous cell carcinoma (in situ)
Authors: Snijders Peter J.F. , Breuer Roderick H.J. , Sutedja Thomas G. , Egging Monique , Voorhorst Feja J. , Steenbergen Renske D.M. , van der Linden Hans C. , Risse Elle K. , Berkhof Johannes , de Vries Elisabeth G.E. , van der Zee Ate G.J. , Postmus Pieter E. , Meijer Chris J.L.M. , Smit Egbert F.
Published: February 2004

Expression levels of hTERT mRNA were investigated by RT‐PCR in tissue specimens of patients with (Group A) and without (Group B) clinically overt bronchial carcinoma, respectively. Bronchial carcinoma (n = 9) and distant normal (n = 9) specimens were analyzed in Group A. The chance of carcinoma seemed to increase with increasing hTERT mRNA levels (OR = 6.04, 95% CI = 1.02–37). Group B was comprised of 21 patients who underwent autofluorescence bronchoscopy. After analysis of 66 bronchial biopsies the chance of prevalent carcinoma in situ or carcinoma increased with increasing hTERT mRNA levels (OR = 6.19, 95% CI = 1.55–25). Variables like age, gender, smoking history, history of cancer within the airways or the degree of lymphocyte infiltrate in the specimens did not modify this relation. In 7 Group B patients in whom bronchial cancer was diagnosed during follow‐up, biopsies taken before cancer diagnosis from both the area of the newly developed tumor and distantly from this area had been analyzed for hTERT expression. The median hTERT mRNA level in the biopsies from the area of future cancer was significantly higher than in biopsies taken from distant sites (p < 0.03). These data indicate that elevated hTERT mRNA is associated with an increased relative risk of prevalent and incident bronchial squamous cell carcinoma (in situ). © 2004 Wiley‐Liss, Inc.
Calix[8]arene‐mediated self‐assembly of tetrapeptide H‐Leu‐Leu‐Ile‐Leu‐OMe
Authors: Satheeshkumar K. S. , Vasu G. , Vishalakshi V. , Moni M. S. , Jayakumar R.
Published: February 2004

Conformational analysis of peptide 1, H‐Leu‐Leu‐Ile‐Leu‐OMe on complexing with macro cycle calix[8]arene has been carried out using 1H‐NMR and FTIR spectroscopic techniques. Stoichiometry of the complex formed in the 1:8 ratio was evidenced by a Job plot. NMR studies of the above peptide show a marked downfield shift and an increase in 3J values for NH resonances on complexing with calix[8]arene. The characteristic NOE connectivity between Ni+1H and CiαH confirm β‐sheet conformation in the complexed state. Both 1H‐NMR and FTIR results indicate that the α‐amino group of Leu I is proximal to the macrocycle and is involved in hydrogen bond formation with phenolic hydrogen atom of the calix[8]arene. This suggests that calix[8]arene provides a suitable platform for peptide 1 to self‐assemble in a parallel β‐sheet conformation. The nature of calix[8]arene interaction with peptide 1 has been studied using dynamic NMR studies, which concludes that a bifurcated hydrogen bonding interaction exists in the molecular interfaces of the assembly. Copyright © 2003 John Wiley & Sons, Ltd.