bluuebunny/crossref_metadata_2025 huggingface dataset:
STRUCTURE AND DIELECTRIC PROPERTIES OFLa-DOPED LEAD STRONTIUM TITANATE THIN FILMS DERIVED FROM SOL–GEL METHOD
Authors: LI X. T. , WU C. , WENG W. J. , HAN G. R. , DU P. Y.
Published: March 2008

A series of ( Pb0.4Sr0.6)1-xLa2x/3TiO3(PSLT) thin films were deposited on ITO/glass substrates by sol–gel technique. Their phase status, surface morphology, and dielectric properties were studied by X-ray diffraction, scanning electron microscope, and impedance analyzer, respectively. Results show that the PSLT thin films were consisted of tetragonal perovskite phase PSLT thin films for x < 0.4, and cubic perovskite phase PSLT thin films for x > 0.4. Dielectric properties such as dielectric constants, dielectric tunabilitis, and inharmonic coefficient were characterized as a function of the film composition.
SYNTHESIS OF Pb(Mg1/3Nb2/3)O3–PbTiO3 FILM ON Ti SUBSTRATES BY A SINGLE STEP AT LOW TEMPERATURE
Authors: CHEN XIULI , FAN HUIQING
Published: March 2008

The relaxor ferroelectric Pb ( Mg 1/3 Nb 2/3) O 3– PbTiO 3 compositions are of interest owing to their excellent dielectric, electromechanical, electro-optical, and other properties. In this paper, the 0.80 Pb ( Mg 1/3 Nb 2/3) O 3–0.20 PbTiO 3 (PMN–PT 80/20) films with pure perovskite structure were synthesized by a single step at 150°C. The corresponding oxides were used as starting materials, namely PbO , MgO , Nb 2 O 5, and TiO 2. By using oxides as precursors, we simplified the hydrothermal process, allowing the process to be more economical. The influences of the Ti metal substrate on the PMN–PT 80/20 films are investigated. By surveying the variations of films, it was suggested that the substrate reacted with the ions in the solution. The films were smooth and homogeneous. There were no cracks and abnormity crystals on the surface of the films. The thickness was about 20 μm. The frequencies dependence of the dielectric properties of PMN–PT 80/20 films was stable even at a high frequency range over 1 MHz.
THE ELECTROCHEMICAL PROPERTIES OF Li/FeS BATTERY USING ELECTROLESS NICKEL PLATED FeS POWDER
Authors: KIM SUNG-HYUN , CHOI YOUNG-JIN , KIM DONG-HUN , JUNG SUNG-HOON , KIM KI-WON , AHN HYO-JUN , AHN JOU-HYEON , GU HAL-BON
Published: March 2008

In order to investigate the electrochemical properties of Li / FeS cell, FeS powder was fabricated by using a high-energy ball milling method. Then, surface of FeS powder was coated with metallic nickel. Nickel coating was conducted by using electroless nickel plating method. Nickel chloride ( NiCl 2 · 6 H 2 O ) was used as the nickel ion source for electroless nickel plating. The effects of nickel coating on the electrochemical properties of FeS electrode for Li/FeS cell were investigated by CV measurement and charge/discharge tests. Then, cells for electrochemical tests were assembled by stacking a lithium anode, separator containing liquid electrolyte, and FeS cathode in turn. From the results, electroless nickel plated FeS electrode showed very high initial discharge capacity of 581 mAh/g- FeS . And also, it showed higher discharge capacity than that of bare FeS electrode until the 29th cycle. Therefore, it is found that metallic nickel gives beneficial effects on enhancing the electrical conductivity of FeS cathode material. 82.47.Cb.
OXIDATION OF AMORPHOUS Cu54Zr22Ti18Ni6 COATING BETWEEN 573 AND 769 K IN AIR
Authors: CHOI J. H. , LEE D. B.
Published: March 2008

Gas-atomized amorphous Cu 54 Zr 22 Ti 18 Ni 6 powders were sprayed onto a steel substrate by the kinetic spraying method to make an amorphous Cu 54 Zr 22 Ti 18 Ni 6 coating. The oxidation behavior of the coating was studied over the temperature range 573–769 K in air. The oxidation products were primarily Cu 2 O , CuO , β- ZrO 2, ZrTiO 4, and Cu . Copper oxides were the major oxides. Preferential oxidation of Cu occurred around the surface of the coating.
EFFECT OF PRE-HEATING TEMPERATURE ON THE CHARACTERISTICS OF SOL–GEL DERIVED LEAD ZIRCONATE TITANATE FILMS
Authors: THOUMTOM SARAWUT , RUJIJANAGUL GOBWUTE , TONTRAKOON JERAPONG , TUNKASIRI TAWEE
Published: March 2008

Effect of pre-heating temperature on the properties of Lead zirconate titanate (PZT) powders and films was investigated. PZT powders and films were prepared via a triol-based sol–gel route. The PZT powders prepared at various heating temperatures were characterized. The preheating temperature range of 200°C–400°C and annealing temperature of 600°C were chosen to make the films. AFM micrograph revealed the thin films with homogeneous, dense, and crack-free properties. The pre-heating temperature was found to have a significant effect on phase formation, prefer orientation, and dielectric properties of the films. Higher dielectric constant and dielectric loss were observed at higher pre-heating temperature. However, all films showed the dielectric loss less than 0.04.
KINETIC MONTE CARLO SIMULATION OF HETEROEPITAXIAL GROWTH OF InSb BUFFER LAYER AND EFFECTS ON InSb/GaAs FILMS
Authors: XIONG M. , LI M. C. , WANG H. L. , ZHAO L. C.
Published: March 2008

InSb films on GaAs (001) substrates have been grown using a two-step method by molecular beam epitaxy (MBE). The Kinetic Monte Carlo (KMC) method, based on solid-on-solid (SOS) model has been introduced to simulate the Volmer–Weber growth of InSb buffer layer on GaAs substrate. The buffer surface becomes rough obviously and produces an undulating profile during the last coverage of the substrate. The undulating buffer surface would play an adverse role in the surface morphology of the following InSb epilayer. Therefore, the growth of InSb epilayer before the formation of undulating buffer surface would get a better surface, which has been convinced by the results of atomic force microscope (AFM) observations.
COMPARISON OF MAGNETIC PROPERTY OF Cu-, Al-, AND Li-DOPED ZnO DILUTE MAGNETIC SEMICONDUCTOR THIN FILMS
Authors: VAN L. H. , DING J. , HONG M. H. , FAN Z. C. , WANG L.
Published: March 2008

The properties of Cu -, Al -, and Li -doped ZnO dilute magnetic semiconductor (DMS) have been analyzed and compared. Zincite with wurtzite structures have been synthesized successfully on SiO 2 (101) and SiO 2 (110) substrates in both the Cu – ZnO and Li – ZnO DMS. The highly textured ZnO (002) peaks were able to form in the Cu – ZnO system at 400°C. However, it formed at even much lower temperature in the Li – ZnO system, that is only 25°C. ZnO (002) peaks in both systems were formed without any impurity phases. However, no crystalline structure is synthesized in the Al – ZnO system. The thin films formed are amorphous. The structural and related magnetic properties of the films were analyzed by XRD, AFM, and VSM. The films were found to be at their highest magnetism at the value of 3.1 emu/cm3 for Co – ZnO and 2.5 emu/cm3 for Li – ZnO , synthesized at 400°C, and under 1 × 10-4 Torr oxygen partial pressure.
SYNTHESIS AND CHARACTERIZATION OF FERROMAGNETIC NANOWIRES USING AAO TEMPLATES
Authors: THONGMEE S. , MA Y. W. , DING J. , YI J. B. , SHARMA G.
Published: March 2008

Ferromagnetic ( Ni , Co , Fe ) nanowires were electrodeposited using AAO template. XRD analysis indicated that the ferromagnetic wires had preferred orientation. For longer deposition time, the nanowires with textured structure changed to single crystal. The investigation on the growth mechanism showed that in the initial stage, the nanowires were polycrystalline. Our TEM analysis revealed the transition from polycrystalline structure to single crystal from the bottom to the top. The growth mechanisms are probably due to the competition growth of the adjacent grains and the confinement of growth in the nano-sized hole of the AAO template.
EFFECTS OF SPUTTERED Ar PRESSURE AND SUBSTRATE TEMPERATURE ON THE MICROSTRUCTURE AND MAGNETIC PROPERTIES OF Cr/SmCo5/Cr FILMS
Authors: ZHEN CONGMIAN , ZHANG JINJUAN , MA LI , HOU DENGLU , LIU YING , LI SHIQIANG
Published: March 2008

Cr / SmCo 5/ Cr films were fabricated by a DC facing targets magnetron sputtering. The influences of sputtered Ar pressure and substrate temperature on their microstructure and magnetic properties were investigated. Magnetic measurements indicate that the optimal substrate temperature was 450°C, and the film deposited at 2 Pa Ar pressure had the largest in-plane coercivity (2403.54 Oe). No SmCo 5 diffraction peaks except Cr (110) peak with body-centered-cubic structure were seen in all the samples by X-ray diffusion. The Needle-like grains of the film deposited at low Ar pressure were observed by atomic force microscope. The domain pattern of the film fabricated at 2 Pa Ar pressure showed more uniform. When the sputtered Ar pressure was 2 Pa, the narrowest switching field distribution (0.57) was obtained, indicating a narrower grain size distribution. The δM value was nearly zero for the film deposited at 2 Pa Ar pressure, and this indicated that there was almost noninteraction between grains.
EFFECTS OF OPERATING CONDITIONS ON THE DEPOSITION OF GaAs IN A VERTICAL CVD REACTOR
Authors: BAEK JAE-SANG , BOO JIN-HYO , KIM YOUN-JEA
Published: March 2008

A numerical study is needed to gain insight into the growth mechanism and improve the reactor design or optimize the deposition condition in chemical vapor deposition (CVD). In this study, we have performed a numerical analysis of the deposition of gallium arsenide ( GaAs ) from trimethyl gallium (TMG) and arsine in a vertical CVD reactor. The effects of operating parameters, such as the rotation velocity of susceptor, inlet velocity, and inlet TMG fraction, are investigated and presented. The three-dimensional model which is used in this investigation includes complete coupling between the thermal-fluid transport and species transport with chemical reaction.
CO-OXIDATION CATALYZED BY NANOCRYSTALLINE CeO2 PARTICLES WITH DIFFERENT MORPHOLOGIES
Authors: PONG W. Y. , CHANG H. Y. , CHEN H. I. , CHANG J. R.
Published: March 2008

Nanocrystalline cerium oxide ( CeO 2) particles prepared by the novel two-stage precipitation method were used for the catalysis of CO oxidation. Firstly, two shapes, i.e. particulate (P-) and needle-like (N-), CeO 2 nanoparticles were formed via proposed temperature-arranged routes. The crystalline structure, morphology, particle size, and surface area of samples were characterized by using XRD, TEM, HRTEM, and BET techniques. Furthermore, the morphological effect of the CeO 2 samples on the catalytic activity of CO oxidation was investigated. From the experimental results, it indicated that the prepared samples were all nonporous and fcc-structured CeO 2. The CeO 2 particles, as precipitating at 90°C for 5 min and then aging at 90°C, were particulate, whereas they were needle-like by aging at 0°C. The CO oxidation reaction showed that the catalytic activity of N- CeO 2 nanoparticles was higher than that of P- CeO 2, attributing from the exposed higher-energy {100} and {110} facets for N- CeO 2 nanoparticles. Moreover, the calcined samples with higher degree of crystallinity showed further promotion in catalytic activity. It was also worthy to note, that by replacing the CeO 2 catalyst by Pd / CeO 2, a large increase in the CO conversion was found, especially catalyzed by Pd /N- CeO 2.
SYNTHESIS AND CHARACTERIZATION OF LiFePO4/C PREPARED VIA A SOL–GEL METHOD
Authors: LIN YAN , PAN HONGGE , GAO MINGXIA , MIAO HE , LI SHOUQUAN , WANG YUE
Published: March 2008

Carbon-coated lithium ion phosphate was synthesized from a gel precursor with ferric iron and a carbon source of organic chelating agent via a sol–gel method. The dependence of the microstructure and electrochemical performance of the synthesized LiFePO 4/ C on the pH value of the precursor solution during gel formation and the sintering time was investigated. The obtained LiFePO 4/ C particles were characterized by X-ray diffraction, field-emission scanning electron microscopy, and element analysis. The results show that the pH value has little effect on the phase purity. At a sintering temperature of 700°C, the discharge capacity of LiFePO 4/ C under 0.1 C (1 C = 170 mA/g) regime decreased from 152.8 to 62.5 mAh/g with decreasing the sintering time from 12 h to 8 h. Appropriate sintering time can lead to well-crystallized LiFePO 4/ C , which improves the electrochemical performance.
DIELECTRIC CHARACTERISTICS OF BST/BZT/BST MULTILAYER
Authors: QIN W. F. , ZHU J. , XIONG J. , TANG J. L. , JIE W. J. , ZHANG Y. , LI Y. R.
Published: March 2008

Ba 0.6 Sr 0.4 TiO 3 (BST) and Ba 0.6 Sr 0.4 TiO 3/ Ba ( Zr 0.2 Ti 0.8) O 3/ Ba 0.6 Sr 0.4 TiO 3 (BST/BZT/BST) multilayer (ML) films were prepared by pulsed laser deposition on the LaNiO 3-coated LaAlO 3 substrate. X-ray diffraction analysis revealed that the two kinds of films could be epitaxially grown in pure single-oriented perovskite phases and atomic force microscopy showed that the grain size of ML films was similar to BST films in size. The dielectric properties of the BST and ML thin films were measured at 10 kHz and 300 K with a parallel-plate capacitor configuration. The results revealed that the dielectric tunability for ML films slightly decreased, while the loss decreased synchronously. The figure-of-merit factor value increases from 17.32 for BST films to 42.14 for ML films under an applied electric field of 300 kV/cm. The leakage current density of the BST thin films at a positive bias field of 300 kV/cm decreases from 3.76 × 10-6 to 1.25 × 10-7 A/cm2 for ML films. This work clearly reveals the highly promising potential of BST/BZT/BST multilayer films compared with BST films for application in tunable microwave devices.
Hyperinsulinemia and impaired leptin-adiponectin ratio associate with endothelial nitric oxide synthase polymorphisms in subjects with in-stent restenosis
Authors: Galluccio Elena , Piatti PierMarco , Citterio Lorena , Lucotti Pietro C. G. , Setola Emanuela , Cassina Laura , Oldani Matteo , Zavaroni Ivana , Bosi Emanuele , Colombo Antonio , Alfieri Ottavio , Casari Giorgio , Reaven Gerald M. , Monti Lucilla D.
Published: March 2008

Little is known about the association of endothelial nitric oxide synthase (NOS3) gene polymorphisms and the presence of insulin resistance and the early evolution of atherosclerosis in nondiabetic subjects with cardiovascular disease (CAD) and stent implantation. The present study was performed in an attempt to better understand whether metabolic, endothelial, and angiographic findings characteristic of subjects with cardiovascular disease and in-stent restenosis are related to NOS3 variants. This is a case-control study performed from 2002 to 2006. All subjects admitted to the study were recruited in the Nord-Centre of Italy, most from Milan and its surrounding towns. Measures of glucose tolerance, insulin sensitivity, markers of endothelial dysfunction, forearm vasodilation, and adipokine levels were determined and associated to the frequency of two single-nucleotide polymorphisms of NOS3, i.e., Glu298Asp (rs1799983, G/T) and rs753482 (intron 18 A/C). A total of 747 subjects, not known to have diabetes, were evaluated: 333 subjects had asymptomatic CAD, 106 subjects had unstable angina and were evaluated for in-stent restenosis 6 mo after stent placement, and 308 were control subjects. The presence of TT and CC minor alleles was significantly greater in case groups compared with control subjects. At phenotypic level, subjects with the polymorphisms were characterized by hyperinsulinemia and reduced reactive hyperemia, whereas increased leptin and decreased adiponectin levels were present in subjects with restenosis in the presence of reduced minimal lumen diameter and length of stenosis almost doubled. Hyperinsulinemia, endothelial dysfunction, and a more atherogenic profile seem to be peculiar features of subjects with asymptomatic CAD and restenosis carrying NOS3 gene variants.
Experiments Needed in Meson and Baryon Spectroscopy
Authors: Bugg D. V.
Published: March 2008

Three (or four) straightforward experiments would contribute greatly to completing the spectroscopy of baryons and light mesons. In the baryon sector, data are needed on inelastic reactions from a polarised target withπ±andK±beams up to∼3 GeV/c. Similar data are needed in the light meson sector forp¯pinteractions in the momentum range 0.3–2 GeV/c. In both cases, valuable information is to be obtained from longitudinal (L) and sideways (S) target polarisations as well as the conventional normal (N) polarisation. Thirdly,3S1and3D1mesons in the mass range 1–2.4 GeV could probably be separated either by diffractive dissociation of transversely polarised photons or bye+e−radiative return experiments using transversely and longitudinally polarised electrons.
Finite Element Formulation of Forced Vibration Problem of a Prestretched Plate Resting on a Rigid Foundation
Authors: Eröz M. , Yildiz A.
Published: March 2008

The three-dimensional linearized theory of elastodynamics mathematical formulation of the forced vibration of a prestretched plate resting on a rigid half-plane is given. The variational formulation of corresponding boundary-value problem is constructed. The first variational of the functional in the variational statement is equated to zero. In the framework of the virtual work principle, it is proved that appropriate equations and boundary conditions are derived. Using these conditions, finite element formulation of the prestretched plate is done. The numerical results obtained coincide with the ones given by Ufly and in 1963 for the static loading case.
Gilbert's Syndrome and Irinotecan Toxicity: Combination with UDP-Glucuronosyltransferase 1A7 Variants Increases Risk
Authors: Lankisch Tim O. , Schulz Christoph , Zwingers Thomas , Erichsen Thomas J. , Manns Michael P. , Heinemann Volker , Strassburg Christian P.
Published: March 2008

Background: Gilbert's syndrome is characterized by a functional promoter single nucleotide polymorphism (SNP) of the UDP-glucuronosyltransferase (UGT) 1A1 gene and represents a pharmacogenetic risk factor for irinotecan toxicity, but study data remain controversial. The active CPT-11 metabolite 7-ethyl-10-hydroxycamptothecin is detoxified by several UGT1A proteins, which include UGT1A7 with a high specific activity that may contribute to the risk of irinotecan toxicity in Gilbert's syndrome patients.

Methods: Genotyping of the UGT1A1*28, UGT1A7 N129K/R131K, and UGT1A7-57T/G variants was done in 105 irinotecan-treated patients with metastatic colorectal cancer; adverse events were documented during all 297 treatment cycles and analyzed by Cochran-Mantel-Haenszel, Mann-Whitney, and χ2 tests.

Results: The presence of UGT1A7 but not UGT1A1 variants was associated with at least one adverse event. In patients combining all three variants, thrombocytopenia and leukopenia were significantly more frequent. The overall incidence of adverse events was significantly higher (P = 0.0035) in carriers of the UGT1A risk alleles, who also had significantly higher rate of dose reductions.

Conclusions: Irinotecan toxicity is more likely in patients with Gilbert's syndrome carrying the UGT1A1*28 allele combined with reduced function UGT1A7 N129K/R131K and UGT1A7-57T/G SNP. Based on the ability of UGT1A7 to metabolize and eliminate the active irinotecan metabolite 7-ethyl-10-hydroxycamptothecin, the UGT1A1/UGT1A7 SNP combination haplotype appears to be a superior risk predictor than Gilbert's syndrome alone. (Cancer Epidemiol Biomarkers Prev 2008;17(3):695–701)
Association of Genetic Variants at 8q24 with Breast Cancer Risk
Authors: Fletcher Olivia , Johnson Nichola , Gibson Lorna , Coupland Ben , Fraser Agnes , Leonard Angela , dos Santos Silva Isabel , Ashworth Alan , Houlston Richard , Peto Julian
Published: March 2008

Recent whole genome association studies of prostate, breast, and colorectal cancer have identified susceptibility loci on 8q24. We genotyped three variants associated with prostate cancer (rs10090154, rs13254738, and rs7000448), one associated with both prostate and colorectal cancer (rs6983267), and one associated with breast cancer (rs13281615) in a series of 1,499 breast cancer cases and 1,390 controls. 1,267 (85%) of the cases had two primary breast cancers. Our analysis provides further evidence of the relationship between rs13281615 and risk of breast cancer, with heterozygote odds ratio (OR) 1.30 95% confidence interval (CI) 1.09-1.54 and homozygote OR 1.52 (95% CI, 1.22-1.89; Ptrend = 0.00003), and confirms the prediction that the risk is substantially higher in this genetically enriched series (OR per allele, 1.24; 95% CI, 1.12-1.38) than in a large series of mainly unselected cases (reported OR per allele, 1.08; 95% CI, 1.05-1.11). We observed a protective effect of rs13254738 for breast cancer (allelic OR, 0.88; 95% CI, 0.78-0.98; P = 0.02), which is supported by the Cancer Genetic Markers of Susceptibility data (pooled allelic OR, 0.88; 95% CI, 0.81-0.96; P = 0.003). None of the other three single nucleotide polymorphisms, two associated with prostate (rs10090154 and rs7000448) and one with both prostate and colorectal cancers (rs6583267), was associated with breast cancer risk in our study. This evidence of a protective effect for breast cancer of one variant (rs13254738) that has been associated previously with a 1.25-fold increased risk of prostate cancer, with no effect for the two other variants, indicates that the effects of the risk alleles clustered at 8q24 are cancer site specific. (Cancer Epidemiol Biomarkers Prev 2008;17(3):702–5)
Cyclooxygenase-2 and Inducible Nitric Oxide Synthase Gene Polymorphisms and Risk of Reflux Esophagitis, Barrett's Esophagus, and Esophageal Adenocarcinoma
Authors: Ferguson Heather R. , Wild Christopher P. , Anderson Lesley A. , Murphy Seamus J. , Johnston Brian T. , Murray Liam J. , Watson R.G. Peter , McGuigan Jim , Reynolds John V. , Hardie Laura J.
Published: March 2008

The incidence of esophageal adenocarcinoma has increased in recent years, and Barrett's esophagus is a recognized risk factor. Gastroesophageal reflux of acid and/or bile is linked to these conditions and to reflux esophagitis. Inflammatory disorders can lead to carcinogenesis through activation of “prosurvival genes,” including cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). Increased expression of these enzymes has been found in esophageal adenocarcinoma, Barrett's esophagus, and reflux esophagitis. Polymorphic variants in COX-2 and iNOS genes may be modifiers of risk of these conditions. In a population-based case-control study, we examined associations of the COX-2 8473 T>C and iNOS Ser608 Leu (C>T) polymorphisms with risk of esophageal adenocarcinoma, Barrett's esophagus, and reflux esophagitis. Genomic DNA was extracted from blood samples collected from cases of esophageal adenocarcinoma (n = 210), Barrett's esophagus (n = 212), and reflux esophagitis (n = 230) and normal population controls frequency matched for age and sex (n = 248). Polymorphisms were genotyped using TaqMan allelic discrimination assays. Odds ratios and 95% confidence intervals were obtained from logistic regression models adjusted for potential confounding factors. The presence of at least one COX-2 8473 C allele was associated with a significantly increased risk of esophageal adenocarcinoma (adjusted odds ratio, 1.58; 95% confidence interval, 1.04-2.40). There was no significant association between this polymorphism and risk of Barrett's esophagus or reflux esophagitis or between the iNOS Ser608 Leu polymorphism and risk of these esophageal conditions. Our study suggests that the COX-2 8473 C allele is a potential genetic marker for susceptibility to esophageal adenocarcinoma. (Cancer Epidemiol Biomarkers Prev 2008;17(3):727–31)
Meta-analysis of Colorectal Cancer Gene Expression Profiling Studies Identifies Consistently Reported Candidate Biomarkers
Authors: Chan Simon K. , Griffith Obi L. , Tai Isabella T. , Jones Steven J.M.
Published: March 2008

Purpose: Elucidation of candidate colorectal cancer biomarkers often begins by comparing the expression profiles of cancerous and normal tissue by performing gene expression profiling. Although many such studies have been done, the resulting lists of differentially expressed genes tend to be inconsistent with each other, suggesting that there are some false positives and false negatives. One solution is to take the intersection of the lists from independent studies. However, often times, the statistical significance of the observed intersection are not assessed.

Methods: Recently, we developed a meta-analysis method that ranked differentially expressed genes in thyroid cancer based on the intersection among studies, total sample sizes, average fold change, and direction of differential expression. We applied an improved version of the method to 25 independent colorectal cancer profiling studies that compared cancer versus normal, adenoma versus normal, and cancer versus adenoma to highlight genes that were consistently reported as differentially expressed at a statistically significant frequency.

Results: We observed that some genes were consistently reported as differentially expressed with a statistically significant frequency (P < 0.05) in cancer versus normal and adenoma versus normal comparisons but not in the cancer versus adenoma comparison.

Conclusion: Our meta-analysis method identified genes that were consistently reported as differentially expressed. A review of some of the candidates revealed genes described previously as having diagnostic and/or prognostic value as well as novel candidate biomarkers. The genes presented here will aid in the identification of highly sensitive and specific biomarkers in colorectal cancer. (Cancer Epidemiol Biomarkers Prev 2008;17(3):543–52)
Cancer Risk in Children with Birth Defects and in Their Families: A Population Based Cohort Study of 5.2 Million Children from Norway and Sweden
Authors: Bjørge Tone , Cnattingius Sven , Lie Rolv Terje , Tretli Steinar , Engeland Anders
Published: March 2008

Background: Cancer and birth defects may share factors that influence risk. A malformation may involve physiologic changes or changes in lifestyle that might affect cancer risks.

Methods: In Norway and Sweden, the population-based medical birth and cancer registries were linked to identify subsequent cancer occurrence in children with birth defects and among their parents and siblings. Altogether, 5.2 million children and their families were included. The standardized incidence ratio (SIR) served as a measure of relative risk.

Results: There was an increased overall cancer risk in individuals with birth defects in the two countries [SIR, 1.7; 95% confidence interval (95% CI), 1.6-1.9], and the increased risk remained into early adulthood. Individuals with malformations in the nervous system were at increased risk of developing cancer in the brain/nervous system (Norway: SIR, 58; 95% CI, 41-80; Sweden: SIR, 8.3; 95% CI, 4.0-15), individuals with Down syndrome were at an increased risk of leukemia (Norway: SIR, 36; 95% CI, 26-48; Sweden: SIR, 36; 95% CI, 28-46), and there was an increased overall cancer risk for individuals with multiple birth defects (Norway: SIR, 5.5; 95% CI, 3.3-8.7; Sweden: SIR, 3.6; 95% CI, 2.2-5.4). There was no increased overall cancer risk among mothers (SIR, 1.0; 95% CI, 1.0-1.0), fathers (SIR, 1.0; 95% CI, 0.9-1.0), and siblings (SIR, 1.0; 95% CI, 0.9-1.1) of children with birth defects.

Conclusions: We observed an increased overall cancer risk in individuals with birth defects. The highest risks were seen for individuals with malformations in the nervous system, Down syndrome, and multiple defects. No increased overall cancer risk was seen among their parents or siblings. (Cancer Epidemiol Biomarkers Prev 2008;17(3):500–6)
NAT2*7 Allele Is a Potential Risk Factor for Adult Brain Tumors in Taiwanese Population
Authors: Liu H. Eugene , Hsiao Pei-Yu , Lee Ching-Chen , Lee Jen-Ai , Chen Hsiang-Yin
Published: March 2008

Arylamine N-acetyltransferase-2 (NAT2) displays extensive genetic polymorphisms that affect the rates of acetylation of drugs and toxic compounds such as amine carcinogens. The association of NAT2 polymorphisms with adult brain tumors has been unclear. To investigate whether the NAT2 genotype is a risk factor of brain tumors, we determined the frequencies of three common polymorphisms in the NAT2 gene, NAT2*5 (T341C), NAT2*6 (G590A), and NAT2*7(G857A), in brain tumor patients and in age- and gender-matched control subjects (n = 27 in each group). Genotyping was carried out using PCR-RFLP and subjects were phenotyped as a fast or slow acetylator based on the genotypes. The odds ratio of NAT2*7 allele frequency was significantly higher in patients with brain tumor than in controls (odds ratio, 6.786; 95% confidence interval, 2.06-22.37; P = 0.003); in the mean time, NAT2*4/*7 genotype was significantly more common in the patient group than in controls (odds ratio, 6.19; 95% confidence interval, 1.68-22.79; P = 0.0039). The tumors in the patients with NAT2*7 allele tended to be high-grade astrocytoma or glioblastoma multiforme (P = 0.016). In conclusion, these data suggest that the presence of NAT2*7 allele might be a potential risk factor for the development of brain tumors in Taiwan. (Cancer Epidemiol Biomarkers Prev 2008;17(3):661–5)
Effect of Tissue Shipping on Plasma Cell Isolation, Viability, and RNA Integrity in the Context of a Centralized Good Laboratory Practice–Certified Tissue Banking Facility
Authors: Ahmann Gregory J. , Chng Wee Joo , Henderson Kimberly J. , Price-Troska Tammy L. , DeGoey Roberta W. , Timm Michael M. , Dispenzieri Angela , Greipp Philip R. , Sable-Hunt Alicia , Bergsagel Leif , Fonseca Rafael
Published: March 2008

The Multiple Myeloma Research Consortium has established a tissue bank for the deposition of bone marrow samples from patients with multiple myeloma to be mailed and processed under good laboratory practices. To date, over 1,000 samples have been collected. At this time, limited information is available on shipped bone marrow aspirates in regards to cell viability, yield, purity, and subsequent RNA yield and quality. To test these determinants, we did a pilot study on behalf of the Multiple Myeloma Research Consortium where samples were drawn at Mayo Clinic Rochester (MCR) pooled and split into two equal aliquots. One-half of each sample was processed following good laboratory practices compliant standard operating procedures, immediately after sample procurement, at MCR. The CD138+ cells were stored at -80°C as a Trizol lysate. The other half of the aspirate was sent overnight to Mayo Clinic Scottsdale where they were processed using identical standard operating procedures. The RNA was extracted and analyzed in a single batch at MCR. At both locations, samples were assayed for the following quality determinants: Viability was assessed using a three-color flow cytometric method (CD45, CD38, and 7-AAD). Cell counts were done to determine plasma cell recovery and post-sort purity determined by means of a slide-based immunofluorescent assay. RNA recovery and integrity was assessed using the Agilent Bioanalyzer. Lastly, gene expression profiles were compared to determine the signature emanating from the shipment of samples. Despite minor differences, our results suggest that shipment of samples did not significantly affect these quality determinants in aggregate. (Cancer Epidemiol Biomarkers Prev 2008;17(3):666–73)
International Correlation between Human Papillomavirus Prevalence and Cervical Cancer Incidence
Authors: Maucort-Boulch Delphine , Franceschi Silvia , Plummer Martyn ,   the IARC HPV Prevalence Surveys Study Group
Published: March 2008

Data from population-based human papillomavirus (HPV) surveys in regions of low, intermediate, and high cervical cancer incidence were used to study the ecologic correlation between high-risk HPV prevalence and cervical cancer incidence. All the surveys were conducted by the IARC according to a standardized protocol for the collection of female population samples and detection of HPV DNA using PCR assay in a central laboratory. Cervical cancer incidence data were extracted, when available, from a cancer registry covering the surrounding or nearby area of the prevalence survey. Thirteen areas were included in this analysis. The relation between high-risk HPV prevalence and cervical cancer incidence was investigated within 10-year age groups from age 25 to 65 years. A Poisson regression model was used to predict cervical cancer incidence from HPV prevalence, and the strength of the correlation was assessed using Spearman’s rank correlation coefficient. The rank correlation was weakest in women ages 25 to 34 years and strongest in women ages 55 to 64 years. In addition, the prevalence of high-risk HPV was not able to predict cervical cancer incidence accurately in every country. Nevertheless, our data raise a concern about the cervical cancer burden in areas where reliable cervical cancer statistics do not exist but where the prevalence of high-risk HPV in women over age 45 is high. (Cancer Epidemiol Biomarkers Prev 2008;17(3):717–20)
Urinary 8-Oxo-7,8-Dihydro-2′-Deoxyguanosine in Patients with Parasite Infection and Effect of Antiparasitic Drug in Relation to Cholangiocarcinogenesis
Authors: Thanan Raynoo , Murata Mariko , Pinlaor Somchai , Sithithaworn Paiboon , Khuntikeo Narong , Tangkanakul Walaluk , Hiraku Yusuke , Oikawa Shinji , Yongvanit Puangrat , Kawanishi Shosuke
Published: March 2008

Parasite infection of Opisthorchis viverrini is a major risk factor for cholangiocarcinoma. Our previous immunohistochemical studies showed that O. viverrini infection induced oxidative DNA lesions in the bile duct epithelium during cholangiocarcinoma development. The current study assessed the levels of 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG), an oxidative DNA lesion, in the urine and leukocytes of O. viverrini–infected subjects and cholangiocarcinoma patients. Forty-nine O. viverrini–infected patients, 55 cholangiocarcinoma patients, and 17 healthy controls were enrolled in the study. We measured 8-oxodG levels in the urine and leukocytes of these subjects using an electrochemical detector coupled to high-performance liquid chromatography. O. viverrini–infected patients were assessed before treatment and 2 months and 1 year after praziquantel treatment. Urinary 8-oxodG levels were significantly higher in cholangiocarcinoma patients (6.83 ± 1.00 μg/g creatinine) than in O. viverrini–infected patients (4.45 ± 0.25 μg/g creatinine; P < 0.05) and healthy subjects (3.03 ± 0.24 μg/g creatinine; P < 0.01) and higher in O. viverrini–infected subjects than in healthy subjects (P < 0.01). The urinary 8-oxodG levels in O. viverrini–infected patients significantly decreased 2 months after praziquantel treatment and were comparable with levels in healthy subjects 1 year after treatment. Urinary 8-oxodG levels were significantly correlated with leukocyte 8-oxodG levels, plasma nitrate/nitrite levels, and aspartate aminotransferase activity. In conclusion, this study, in addition to our previous studies, indicates that 8-oxodG formation by parasite infection may play an important role in cholangiocarcinoma development. Urinary 8-oxodG may be a useful biomarker to monitor not only infection but also carcinogenesis. (Cancer Epidemiol Biomarkers Prev 2008;17(3):518–24)
Nonsteroidal Anti-inflammatory Drug Use and Serum Total Estradiol in Postmenopausal Women
Authors: Hudson Alana G. , Gierach Gretchen L. , Modugno Francesmary , Simpson Jennifer , Wilson John W. , Evans Rhobert W. , Vogel Victor G. , Weissfeld Joel L.
Published: March 2008

Laboratory and epidemiologic evidence suggest that nonsteroidal anti-inflammatory drug (NSAID) use may be inversely related to the risk of breast cancer; however, the mechanism by which NSAIDs may protect against the development of this disease is uncertain. The objective of this observational study was to assess the relationship between current NSAID use and endogenous estradiol levels, an established breast cancer risk factor. To evaluate this aim, we conducted a cross-sectional investigation among 260 postmenopausal women who were not recently exposed to exogenous hormones. Information on current NSAID use (aspirin, cyclooxygenase-2 inhibitors, and other NSAIDs combined) was collected using a questionnaire at the time of blood draw. Estradiol was quantified in serum by radioimmunoassay. General linear models were used to evaluate the association between NSAID use and serum total estradiol. The age-adjusted and body mass index–adjusted geometric mean serum estradiol concentration among NSAID users (n = 124) was significantly lower than nonusers of NSAIDs (n = 136; 17.8 versus 21.3 pmol/L; P = 0.03). Further adjustment for additional potential confounding factors did not substantially alter estimates (17.7 versus 21.2 pmol/L; P = 0.03). To our knowledge, this report is the first to examine the relationship between NSAID use and serum estradiol in postmenopausal women. These cross-sectional findings suggest that NSAID use may be associated with lower circulating estradiol levels, potentially representing one mechanism through which NSAIDs exert protective effects on breast cancer. (Cancer Epidemiol Biomarkers Prev 2008;17(3):680–7)
Metabolism of the Tobacco-Specific Carcinogen 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanone to Its Biomarker Total NNAL in Smokeless Tobacco Users
Authors: Hecht Stephen S. , Carmella Steven G. , Stepanov Irina , Jensen Joni , Anderson Amanda , Hatsukami Dorothy K.
Published: March 2008

The tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is one of the most abundant carcinogens in smokeless tobacco products. NNK uptake by measurement of the urinary metabolites 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and its glucuronides (total NNAL) has been reported in many studies, but there are no data in the literature on the percentage of the NNK dose that is converted to NNAL in smokeless tobacco users. In this study, 15 male subjects abstained from tobacco use for 3 weeks before placing 2 g smokeless tobacco between their cheeks and gums for 30 min. They then continued abstinence and collected three consecutive 24-h urine samples. The amount of NNK in the tobacco before and after use was determined along with the amount in expectorated saliva. The NNK dose thus calculated was compared with the amount of total NNAL excreted in the next 72 h. These data, taken together with previous pharmacokinetic data, show that the percent conversion of NNK to total NNAL in smokeless tobacco users is ∼14% to 17%. This figure can be used to calculate daily exposure to NNK in smokeless tobacco users (∼6 μg). The results of this study also indicate that metabolic activation of NNK to intermediates that can react with DNA is its major pathway of metabolism in smokeless tobacco users. (Cancer Epidemiol Biomarkers Prev 2008;17(3):732–5)
Mutation of human plasminogen kringle 1–5 enhances antiangiogenic action via increased interaction with integrin αvβ3
Authors: Chang Po-Chiao , Chang Yu-Jia , Wu Hua-Lin , Chang Chin-Wei , Lin Chung-I. , Wang Wei-Chih , Shi Guey-Yueh
Published: March 2008

Angiogenesis plays a primary role in tumor growth and metastasis. Angiostatin, a proteolytic fragment containing the first four kringle domains of human plasminogen, can inhibit angiogenesis. The anti-angiogenic activities of kringle 1–5 (K1–5) and kringle 5 fragments of plasminogen are greater than angiostatin in inhibiting angiogenesis and angiogenesis-dependent tumor growth. To further optimize kringle fragment anti-angiogenic activities, mutations were created at the potential glycosylation sites Asn-289 and Thr-346 and the Lys binding site, Leu-532, at kringle 5, including K1–5N289A (replacing Asn by Ala at residue 289), K1–5T346A, K1–5L532R, K1–5N289A/T346A, K1–5T346A/ L532R, K1–5N289A/L532R, and K1–5N289A/T346A/L532R. Wild-type and mutant K1–5 proteins were expressed successfully by the Pichia pastoris expression system. Native K1–5 from proteolytic cleavage and wild-type K1–5 have similar activity in inhibiting basic fibroblast growth factor-induced endothelial cell proliferation. Among these mutated proteins, K1–5N289A/ T346A/L532R exhibited the greatest effect in inhibiting endothelial cell proliferation and in inducing endothelial cell apoptosis. Integrin αvβ3-mediated adhesion of K1–5N289A/ T346A/L532R to endothelial cells was more greatly enhanced when compared to wild type K1–5. Furthermore, K1–5N289A/ T346A/L532R was most potent in inhibiting basic fibroblast growth factor-induced angiogenesis in Matrigel assay in vivo. Angiogenesis-dependent tumor growth was inhibited by systemically injected K1–5N289A/T346A/L532R into mice. These results demonstrate that alteration of glycosylation and Lys binding properties could increase the anti-angiogenic action of K1–5, possibly via enhanced interaction with integrin αvβ3 in endothelial cells.
Prolonged in-vivo half-life of factor VIIa by fusion to albumin
Authors: Weimer Thomas , Wormsbächer Wilfried , Kronthaler Ulrich , Lang Wiegand , Liebing Uwe , Schulte Stefan
Published: March 2008

For the treatment of haemophilia patients with inhibitors, recombinant factor VIIa (rFVIIa) is available as a therapeutic option to control bleeding episodes with a good balance of safety and efficacy. However, the short in-vivo half-life of approximately 2.5 hours makes multiple injections necessary, which is inconvenient for both physicians and patients. Here we describe the generation of a recombinant FVIIa molecule with an extended half-life based on genetic fusion to human albumin. The recombinant FVII albumin fusion protein (rVII-FP) was expressed in mammalian cells and upon activation displayed a FVII activity close to that of wild type FVIIa. Pharmacokinetic studies in rats demonstrated that the half-life of the activated recombinant FVII albumin fusion protein (rVIIa-FP) was extended six- to sevenfold compared with wild type rFVIIa. The in-vitro and in-vivo efficacy was evaluated and was found to be comparable to a commercially available rFVIIa (NovoSeven®). The results of this study demonstrate that it is feasible to develop a half-life extended FVIIa molecule with haemostatic properties very similar to the wild-type factor.
Inherited thrombophilic abnormalities and risk of portal vein thrombosis
Authors: Galli Matteo , Gianni Monica , Ageno Walter , Dentali Francesco
Published: March 2008

Inherited thrombophilic abnormalities may have a role in the development of portal vein thrombosis (PVT).However, the prevalence of these factors in patients with PVT has been evaluated only in small studies with non-conclusive results. It was the purpose of this study to assess the risk of PVT associated with factorV Leiden (FVL) and G20210A prothrombin mutation (PTM). The MEDLINE, EMBASE, Cochrane Library databases, reference lists of retrieved articles and contact with content experts were used. Studies carried out in Western Europe comparing the prevalence of prothrombotic abnormalities in patients with PVT and in controls without a history of thromboembolic disease were included. Two reviewers independently selected studies and extracted study characteristics, quality and outcomes. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for each trial and pooled using a fixed and random-effects model. Statistical heterogeneity was evaluated using the I2 statistic. Sensitivity analyses were performed examining separately studies according to the etiology of PVT and to control population. Twelve studies involving more than 3,000 patients were included. The pooled OR for PVT was 1.90 (95%CI: 1.25, 2.90) in patients with FVL and 4.48 (95%CI: 3.10, 6.48) in patients with PTM. In conclusion, PVT is associated with the presence of FVL and PTM in Western Europe.
Death due to recurrent thromboembolism among younger healthier individuals hospitalized for idiopathic pulmonary embolism
Authors: Zhou Hong , Murin Susan , White Richard
Published: March 2008

The incidence of death due to recurrent pulmonary embolism (PE) after a first-time idiopathic PE is not well defined. We conducted a retrospective study of patients age 18 to 56 years who had idiopathic PE between 1994–2001.The incidence and cause of death within five years was determined using linked discharge records and a master death registry. A total of 3,456 patients had a first-time idiopathic PE. The rate of recurrent VTE 0–6 months after the index event was 13.1%/year, and 2.9%/year 6–60 months after the event. During the mean follow-up of 3.2 years 118 (3.4%, 95% confidence interval [CI]=2.8–4.1%) patients died. Fifty-two (44%) deaths occurred <29 days after the index PE (case-fatality rate =1.5%,95%CI=1.1–2.0%). Among the 66 cases (1.9%) that died after 28 days, 18 (0.52%) were due to recurrent PE or its sequelae: eight had recurrent PE alone, five had recurrent PE and a serious co-morbid illness, and five had thromboembolic pulmonary hypertension with or without acute PE. The person-time rate of death (deaths per 100 patientyears) attributed to any recurrent thromboembolism 6–60 months after the event was 0.16% (95%CI=0.1–0.26%). Ten of the 18 (56%) late thromboembolic deaths reflected a first-time recurrent PE. The 28-day case-fatality rate for recurrentVTE was 2.8% (95%CI= 1.5–4.9%).In this cohort of younger patients with idiopathic PE, the rate of death due to recurrentVTE, particularly to first-time recurrent PE, was low. Among the patients who died of thromboembolism >28 days after the index PE, 28% had developed pulmonary hypertension.
Allosteric regulation of αIIbβ3 by β3 95–105
Authors: Haas Thomas
Published: March 2008

The linear recognition sequences of an anti-β3 antibody that blocked platelet aggregation were identified using β3 tryptic peptides. Two of these recognition sequence-containing peptides were mapped to β3 92–105, and antibodies affinity purified using these peptides blocked platelet aggregation. Examining the structure of αIIbβ3 identified β3 95–105 as the solvent accessible sequence within β3 92–105. A peptide corresponding to β3 95–105 was synthesized and used to affinity purify the β3 antibody. Anti-β3 95–105 completely blocked platelet aggregation and agonist-induced fibrinogen binding to platelets, but had no effect on cyclic-RGD binding. Binding of anti-β3 95–105 to αIIbβ3 also did not alter the structure of the αIIb cap subdomain, as measured by anti-αIIb 201–217 binding. β3 95–105 and peptides spanning two adjacent sequences in the structure of β3 did not bind fibrinogen and were ineffectual in blocking agonist-induced platelet aggregation. Structure analysis revealed that β3 95–105 is adjacent to one of the two hinges in β3 that allows for the outward swing of the hybrid and PSI domains which is central to the conversion of αIIbβ3 from a low into a high affinity state.Thus, the binding of an antibody to β3 95–105 could serve as a fulcrum for allosteric regulation of αIIbβ3 by regulating the movement of the hybrid-PSI domain.