bluuebunny/crossref_metadata_2025 huggingface dataset:
Mucochloric Acid: A Useful Synthon for the Selective Synthesis of 4‐Aryl‐3‐chloro‐2(5H)‐furanones, (Z)‐4‐Aryl‐5‐[1‐(aryl)methylidene]‐3‐chloro‐2(5H)‐furanones and 3,4‐Diaryl‐2(5H)‐furanones
Authors: Bellina Fabio , Anselmi Chiara , Martina Francesca , Rossi Renzo
Published: June 2003

3,4‐Dichloro‐2(5H)‐furanone, which has been prepared efficiently from mucochloric acid, has been transformed selectively into 4‐aryl‐3‐chloro‐2(5H)‐furanones either by Suzuki‐ or Stille‐type reactions. These monochloro derivatives have been used as precursors either to (Z)‐4‐aryl‐5‐[1‐(aryl)methylidene]‐3‐chloro‐2(5H)‐furanones, including naturally occurring rubrolide M, or to unsymmetrical 3,4‐diaryl‐2(5H)‐furanones. Some 2(5H)‐furanone derivatives so prepared have been found to exhibit significant cytotoxic activity in vitro against the NCI three‐cell‐line panel, but limited cytotoxicity against the NCI human tumor 60 cell‐line panel. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Shake table tests on a mass eccentric model with base isolation
Authors: Samali Bijan , Wu Yi Min , Li Jianchun
Published: June 2003

A mass eccentric structure is usually more seismically vulnerable than its concentric counterpart because of the coupled torsional–translational response of such structures. In this work, dynamic characteristics and response of a five‐storey benchmark model with moderate mass eccentricity were investigated using a shake table, simulating four different ground motions. The effectiveness of laminated rubber bearings (LRB) and lead‐core rubber bearings (LCRB) in protecting eccentric structures was examined and evaluated in relation to translational and torsional responses of the benchmark model. It was observed that both translational and torsional responses were significantly reduced with the addition of either a LRB or LCRB isolated system regardless of the nature of ground motion input. The LRB were identified to be more effective than LCRB in reducing model relative displacements, the relative torsional angle as well as accelerations, and therefore provided a better protection of the superstructure and its contents. On the other hand, LCRB rendered a smaller torsional angle and absolute displacement of the base isolation system, hence a more stable structural system. Copyright © 2003 John Wiley & Sons, Ltd.
An advanced analytical model for high damping rubber bearings
Authors: Tsai C. S. , Chiang Tsu‐Cheng , Chen Bo‐Jen , Lin Shih‐Bin
Published: June 2003

Base‐isolation technologies have been developed over the years in attempts to mitigate the effects of earthquakes on structures and potentially vulnerable contents in earthquake prone areas of the world. The high damping rubber bearing (HDRB) is a relatively recent and evolving technology of this kind. The isolator shifts the fundamental period of the base‐isolated structure to a value beyond the range of the plentiful energy‐containing periods of earthquake motions and supplies significant damping to dissipate energy caused by motions. Nevertheless, the highly non‐linear mechanical behaviour of the HDRB is so complex, especially at large strains, that it is difficult to model it analytically. In this paper, an extensive study of experimental tests for identifying the mechanical characteristics of the HDRB is presented. By modifying the Wen's model to include the rate‐dependent effects, an advanced analytical model in an incremental form for the HDRB is also proposed. A very good agreement between the analytical and experimental results has been obtained. It is illustrated that the proposed mathematical model can predict well the mechanical behaviour of HDRB bearings, even at large shear strain. Copyright © 2003 John Wiley & Sons, Ltd.
Dynamic analysis of structures using modified Lanczos co‐ordinates
Authors: Kim Byoung‐Wan , Jung Hyung‐Jo , Kim Woon‐Hak , Lee In‐Won
Published: June 2003

An efficient dynamic analysis method using the modified Lanczos co‐ordinates is presented. The proposed method is obtained by applying the modified Lanczos algorithm using Lanczos vectors that satisfy the stiffness‐orthonormality condition to the conventional Lanczos co‐ordinates method. The modified Lanczos co‐ordinates method is more efficient than the conventional method in the case of structures under multi‐input loads. The effectiveness of the modified Lanczos co‐ordinates method is verified by analysing a numerical example. Copyright © 2003 John Wiley & Sons, Ltd.
Evaluating foundation mass, damping and stiffness by the least‐squares method
Authors: Ju S. H.
Published: June 2003

This paper discusses how to use the three‐dimensional (3D) time‐domain finite‐element method incorporating the least‐squares method to calculate the equivalent foundation mass, damping and stiffness matrices. Numerical simulations indicate that the accuracy of these equivalent matrices is acceptable when the applied harmonic force of 1+sine is used. Moreover, the accuracy of the least‐squares method using the 1+sine force is not sensitive to the first time step for inclusion of data. Since the finite‐element method can model problems flexibly, the equivalent mass, damping and stiffness matrices of very complicated soil profiles and foundations can be established without difficulty using this least‐squares method. Copyright © 2003 John Wiley & Sons, Ltd.
Dispersion analysis of the least‐squares finite‐element shallow‐water system
Authors: Le Roux D. Y. , Carey G. F.
Published: June 2003

The frequency or dispersion relation for the least‐squares mixed formulation of the shallow‐water equations is analysed. We consider the use of different approximation spaces corresponding to co‐located and staggered meshes, respectively. The study includes the effect of Coriolis, and the dispersion properties are compared analytically and graphically with those of the mixed Galerkin formulation. Numerical solutions of a test problem to simulate slow Rossby modes illustrate the theoretical results. Copyright © 2003 John Wiley & Sons, Ltd.
Numerical wave tank based on a σ‐transformed finite element inviscid flow solver
Authors: Turnbull M. S. , Borthwick A. G. L. , Taylor R. Eatock
Published: June 2003

Inviscid two‐dimensional free surface wave motions are simulated using a σ‐transformed finite‐element model based on potential theory for irrotational, incompressible fluid flow over a flat fixed bed. The free surface boundary condition is fully non‐linear, and so non‐linear effects up to very high order can be modelled. The σ‐transformation involves linear stretching of the mesh between the bed and free surface. This has two major advantages. First, remeshing due to the moving free surface is avoided. Second, the mesh nodes are aligned vertically, allowing a high order calculation of the free surface vertical velocity component to be implemented without smoothing, except for very steep waves. The model however is further restricted to non‐overturning, non‐breaking waves because of the uniqueness of the σ‐transformation. Excellent agreement is obtained with analytical and alternative numerical data for small amplitude free sloshing in a rectangular tank and forced sloshing in a horizontally base‐excited rectangular tank. At higher amplitudes, non‐linear effects are evident in the simulations by the present numerical model. The model is also able to reproduce steep progressive waves due to a wave‐maker in agreement with Stokes 5th theory, second‐order shallow water waves in agreement with cnoidal theory, and focused wave groups that match the experimental measurements acquired by Baldocket al. [A laboratory study of non‐linear surface waves on water.Phil. Trans. R. Soc. Lond. A 1996;354:649–676]. Copyright © 2003 John Wiley & Sons, Ltd.
A time‐implicit high‐order compact differencing and filtering scheme for large‐eddy simulation
Authors: Rizzetta D. P. , Visbal M. R. , Blaisdell G. A.
Published: June 2003

This work investigates a high‐order numerical method which is suitable for performing large‐eddy simulations, particularly those containing wall‐bounded regions which are considered on stretched curvilinear meshes. Spatial derivatives are represented by a sixth‐order compact approximation that is used in conjunction with a tenth‐order non‐dispersive filter. The scheme employs a time‐implicit approximately factored finite‐difference algorithm, and applies Newton‐like subiterations to achieve second‐order temporal and sixth‐order spatial accuracy. Both the Smagorinsky and dynamic subgrid‐scale stress models are incorporated in the computations, and are used for comparison along with simulations where no model is employed. Details of the method are summarized, and a series of classic validating computations are performed. These include the decay of compressible isotropic turbulence, turbulent channel flow, and the subsonic flow past a circular cylinder. For each of these cases, it was found that the method was robust and provided an accurate means of describing the flowfield, based upon comparisons with previous existing numerical results and experimental data. Published in 2003 by John Wiley & Sons, Ltd.
Thermal properties of cowpea flour: A study by differential scanning calorimetry
Authors: Henshaw Folake O. , McWatters Kay H. , Akingbala John O. , Chinnan Manjeet S.
Published: June 2003

The thermal properties of 12 varieties of cowpea flour were studied by differential scanning calorimetry (DSC). Flour samples were prepared to a paste of 60% moisture content and sealed in standard DSC pans. Samples were scanned at a heating rate of 5°C/min over a scan range of 40–130°C. Samples exhibited single major endotherms, which occurred over varied temperatures. The transition enthalpy (ΔH) ranged between 1.4 J/g and 4.7 J/g. Transition onset (To) and transition peak (Tp) temperatures ranged between 75–78°C and 78–82°C, respectively. All the DSC parameters measured varied significantly among the varieties. The transition enthalpy (ΔH) was the most discriminating parameter and accounted for 80% of the total variance. The major chemical components of cowpea flour, starch amylose and protein are significant predictors of ΔH. Protein denaturation appears to be a significant modification which occurs during processing of cowpea seeds to flour. The transition enthalpy ΔH could become an important functional index of cowpea flour when related to some quality parameters in products that contain the flour.
Differentiation of toxigenic Staphylococcus aureusin staphylococcal isolates from prepared and frozen foods by combined arbitrarily primed polymerase chain reaction and DNA probe
Authors: Córdoba M. G. , Jordano R. , Aranda E. , Benito M. J. , Córdoba J. J.
Published: June 2003

In prepared and frozen flamenquín and hake fish fingers Staphylococcus aureus as sanitary hazards have been detected. In the present work, a combined method that includes an arbitrarily primed PCR (AP‐PCR) and a mixed DNA probe hybridisation designed for the enterotoxigenic genes sea, seb, sec, and sed will be assayed to differentiate enterotoxigenic S. aureus from other staphylococcal species isolated during the processing of prepared and frozen foods. From the protocols tested for the AP‐PCR, the highest number of amplification bands showing the best resolution was achieved at 30°C annealing and 35°C extension temperatures. Several staphylococci identified by a biochemical test as S. aureus showed in the AP‐PCR analysis different banding patterns to the references S. aureus. The isolates, were investigated by slot blot hybridisation for genes encoding A, B, C, and D staphylococcal enterotoxins to determine their enterotoxigenic potential. Several isolates characterised by the AP‐PCR analysis as S. aureus hybridised with the DNA probe mixture. The combined AP‐PCR and DNA probe hybridisation assayed was able to differentiate toxigenic S. aureus from other staphylococcal species from prepared and frozen foods. This method could be considered as microbial quality assurance in these products.
Mathematical modeling of Saccharomyces cerevisiae inactivation under high‐pressure carbon dioxide
Authors: Erkmen Osman
Published: June 2003

High‐pressure carbon dioxide inactivation curves of Saccharomyces cerevisiae at different temperatures were analysed using the modified Gompertz model. Comparable λ and μ values were obtained under pressure treatment as function of temperature. The phase of disappearance (λ) and the inactivation rate (μ) of S. cerevisiae were inversely related. Higher μ values were obtained at 50°C than at 40, 30, and 20°C under 10.0 MPa CO2 pressure. Increased pressure and temperature had significant effects on the survival of S. cerevisiae. Arrhenius, linear and square‐root models were used to analyse the temperature dependence of the inactivation rate constant. For the Arrhenius model the activation energy (Eμ) was 56.49 kJ/mol at 10.0 MPa, and 55.70, 53.83, and 52.20 kJ/mol at 7.5, 5.0, and 2.5 MPa, respectively. Results of this study enable the prediction of yeast inactivation exposed to different CO2 pressures and temperatures.
Phenolic constituents and antioxidant capacities of Crataegus monogyna (Hawthorn) callus extracts
Authors: Bahorun Theeshan , Aumjaud Esha , Ramphul Hemlata , Rycha Maheshwaree , Luximon‐Ramma Amitabye , Trotin Francis , Aruoma Okezie I.
Published: June 2003

Crataegus (Hawthorn) has long been used as a folk medicine and is widely utilized in pharmaceutical preparations mainly because of its neuro‐ and cardiosedative actions and its low toxicity. The pharmacological effects of Crataegus have mainly been attributed to the polyphenolic contents. In this study, the production of polyphenols by ten‐year‐old Crataegus monogyna calli was studied in relation to growth variation and antioxidant capacity within a subculture period. Assays based on the Trolox equivalent antioxidant capacity (TEAC( ferric reducing antioxidant power (FRAP) and stability in oil‐in‐water emulsion were used to characterize the antioxidant actions of the callus cultures. High TEAC (3.66 μmol/g dry weight) and FRAP (208.19 μmol Fe2+/g dry weight) values were observed when maximal growth was reached (days 30–35( and this seemed to be influenced by optimum total phenol (47.40 mg/g dry weight( proanthocyanidin (20.81 mg/g dry weight( flavonoid (7.01 mg/g dry weight( anthocyanin (6.18 mg/g dry weight( (–)‐epicatechin (1.77 mg/g dry weight( procyanidin B2 (3.97 mg/g dry weight( and chlorogenic acid (1.11 mg/g dry weight) production during that period. The TEAC values were strongly associated with total flavonoids and to a lesser extent with total phenols, anthocyanins and total proanthocyanidins. The FRAP antioxidant values correlated to total phenols, proanthocyanidins and flavonoids, respectively. The polyphenolic rich calli were as effective as butylated hydroxytoluene (BHT) in preventing hydroperoxide and conjugated diene formation in a 30% oil‐in‐water emulsion prepared with stripped sunflower oil, during 7 days storage at 30°C. Crataegus monogyna cell culture represents an important alternative source for natural antioxidants.
Characterisation and quantification of the reaction(s) catalysed by transglutaminase using the o‐phthaldialdehyde reagent
Authors: Flanagan John , FitzGerald Richard J.
Published: June 2003

The potential application of the o‐phthaldialdehyde (OPA) reagent for quantification of the type and extent of the reaction(s) catalysed by transglutaminase (TGase) during incubation with sodium caseinate (NaCN) was investigated. Initial studies were performed to ensure that NH3, a by‐product of TGase activity, could be determined with the OPA reagent in trichloroacetic acid (TCA) supernatants of NaCN solutions. The detectable concentration of exogenously added NH3 (at NH3 concentrations > 10 mM) was found to decrease during extended incubation at 23, 37 and 50°C and at either pH 7.0 or 8.0 in 4% w/v NaCN solutions, even when taking into account the evaporation of water from the sample. The recovery of NH3 from 12% w/v TCA supernatants of NaCN solutions spiked with 5 mM NH3 at 23°C and pH 7.0 was found to be 88%. The release of NH3 and the decrease in ε‐amino groups on incubating NaCN with TGase was subsequently quantified using the OPA reagent. Incubation of NaCN (4% w/v) with TGase at 23°C resulted in progressive increases and decreases, respectively, in NH3 and ε‐amino group concentration with increased incubation time. These changes were dependent on TGase : NaCN. It was estimated that approximately 20% of the available Lys residues in NaCN were involved in TGase‐catalysed cross‐links. However, the observed decrease in ε‐amino group concentration was higher than expected. This may be due to concealment of noncross‐linked amino groups in polymerised NaCN, making them unavailable for reaction with the OPA reagent.
The effect of water content on proton transport in polymer electrolyte membranes
Authors: Commer P. , Cherstvy A.G. , Spohr E. , Kornyshev A.A.
Published: June 2003

We investigate proton transport in a polymer electrolyte membrane using continuum theory and molecular dynamics (MD) computer simulations. Specifically our goal is to understand the possible molecular origin of the effect of water content on the activation energy (AE) and pre‐exponential factor of proton conductivity, in comparison with experimental observations reported for Nafion, where a decrease of AE with increasing water content has been observed. We study proton diffusion in a single pore, using a slab‐like model. We find that although the average proton diffusion coefficient is several times smaller in a narrow pore than in a wide water‐rich pore, its AE is almost unaffected by the pore width. This contradicts an earlier proposed conjecture that the sizable Coulomb potential energy barriers near the lattice of immobile point‐like SO3– groups increase the AE in a narrow pore. Here we show that these barriers become smeared out by thermal motion of SO3– groups and by the spatial charge distribution over their atoms. This effect strongly diminishes the variation of the AE with pore width, which is also found in MD simulations. The pre‐exponential factor for the diffusion process, however, decreases, indicating a limited number of pathways for proton transfer and the freezing out of degrees of freedom that contribute to the effective frequency of transfer. Decreasing the pore size diminishes bulk‐like water regions in the pore, with only less mobile surface water molecules remaining. This hampers proton transfer. The increase of AE takes place only if the thermal motion of the SO3– head groups freezes out simultaneously with decreasing water content, but the effect is not profound. The stronger effect observed experimentally may thus be associated with some other rate‐determining consecutive process, concerned with polymer dynamics, such as opening and closing of connections (bridges) between aqueous domains in the membrane under low water content.
Radioactive Labeling Study and FTIR Measurements of Methanol Adsorption and Oxidation on Fuel Cell Catalysts
Authors: Coutanceau C. , Hahn F. , Waszczuk P. , Wieckowski A. , Lamy C. , Léger J.‐M.
Published: June 2003

The adsorption and the electrooxidation of methanol‐derived surface CO on fuel‐cell grade platinum and platinum‐ruthenium alloy nanoparticle catalysts were studied using a combination of electrochemical measurements and radioactive labeling (thin foil radioactive labeling technique) and in situ infrared reflectance spectroscopy. The kinetics of formation of surface and bulk products coming from methanol and surface/bulk exchange processes were found to be significantly different on Pt compared to Pt/Ru. The observed difference in the kinetics of CO adsorption underlines the electronic effect in the surface catalytic activity due to modification of the electronic structure of surface platinum atoms by ruthenium. Correlation between FTIR and radiolabeling measurements indicated that the adsorption of CO from methanol is a very slow process at low potential but that the coverage by CO poison is greater at higher potential. Then, the results obtained from both analytical techniques (in situ IR reflectance spectroscopy and radioactive labeling method) displayed very good agreement and allowed us to validate them for the investigation of the methanol oxidation mechanism.
Performance of a DMFC Using Pt‐Ru/C Catalysts Prepared by Reduction with Formic Acid
Authors: Lizcano‐Valbuena W.H. , de Souza A. , Paganin V.A. , Leite C.A.P. , Galembeck F. , Gonzalez E.R.
Published: June 2003

In this work Pt‐Ru/C catalysts are prepared in different atomic ratios by reduction with formic acid and submitted to thermal treatment in a hydrogen atmosphere. Physical characterisation of the materials by XRD, EDX, and TEM shows that the particle size increases as a consequence of the thermal treatments and this effect is relevant in the electrochemical behaviour of these materials in a DMFC. Finally, the performance of the DMFC with different flow fields is examined.
Dynamic Modeling and Simulation of a Countercurrent Molten Carbonate Fuel Cell (MCFC) with Internal Reforming
Authors: Heidebrecht P. , Sundmacher K.
Published: June 2003

A dynamic mathematical model for a countercurrent MCFC with direct internal methane reforming is introduced. It allows for the simulation of the gas phase compositions and flows, the temperatures in gas and solid phases, the cell voltage, and the current density distribution. This state space model is fully formulated in terms of dimensionless parameter groups, which are derived from the underlying physical and chemical phenomena. The model assumptions and equations are outlined in detail and a numerical solution strategy is proposed. The model is used to predict the current‐voltage curve as well as the dynamic cell response to a stepwise load change.
Genomic imbalances in CML blast crisis: 8q24.12–q24.13 Segment identified as a common region of over‐representation
Authors: Gribble Susan M. , Reid Alistair G. , Roberts Ian , Grace Colin , Green Anthony R. , Nacheva Elizabeth P.
Published: June 2003

The acute phase of chronic myeloid leukemia (CML) is accompanied by secondary chromosomal changes. The additional changes have a non‐random pattern; however, highly abnormal (marker) chromosomes are reported in some 20% of abnormal karyotypes. These marker chromosomes have proved to be beyond the resolution of conventional G‐banding analysis. We used molecular cytogenetic techniques to determine the structure of complex chromosome markers in 10 CML‐derived cell lines after our investigations of CML patients in blast crisis. Multicolor fluorescence in situ hybridization identified a multitude of structural chromosome aberrations. In addition, genomic gains identified by comparative genomic hybridization (CGH) were mapped to highly complex marker chromosomes in more than one cell line. The most common genomic loss detected by CGH affected chromosome 9, whereas the most common genomic gains affected, in order of frequency, the sequences of 8q, 6, and 13q. The smallest discrete amplification on 8q was identified in cell line MEG‐01. This amplicon contains sequences represented by the marker D8S263/RMC08P029 but did not contain the proximal MYC gene or a more distal marker, D8S256/RMC08P025. We determined the size of the amplicon to be less than the chromosome segment 8q24.12–q24.13. The use of region‐ and locus‐specific probes to analyze the organization of highly complex marker structures aided the identification of preferentially amplified genomic regions. The resultant amplifications could harbor gene(s) driving disease progression. © 2003 Wiley‐Liss, Inc.
Molecular characterization of acute leukemias by use of microarray technology
Authors: Kohlmann Alexander , Schoch Claudia , Schnittger Susanne , Dugas Martin , Hiddemann Wolfgang , Kern Wolfgang , Haferlach Torsten
Published: June 2003

Accurate subclassification of leukemia and the identification of prognostic determinants are essential to guide therapy and to improve patients' outcome. According to present standards, pre‐therapeutic assessment depends on a combination of different methods. We aimed to expand the molecular characterization of different acute leukemia subtypes to identify new genome‐wide diagnostic markers. Total RNA from 90 adult patients suffering from acute lymphoblastic leukemia (ALL, n = 25) and acute myeloid leukemia (AML, n = 65) was extracted at diagnosis and high density oligonucleotide microarrays were used to analyze the expression profiles of 12,000/22,000 genes in all specimens (Affymetrix U95Av2/U133A). All cases were thoroughly characterized by individual combinations of cytomorphology, cytogenetics, multiparameter immunophenotyping, and molecular genetics. The expression signature of a small set of differentially expressed genes was sufficient to accurately discriminate eight clinically relevant acute leukemia subgroups. Underlying chromosomal aberrations or immunophenotypical characteristics were strictly correlated with a distinct gene expression pattern for AML with t(8;21), t(15;17), t(11q23)/MLL, or inv(16) as well as for precursor B‐ALL with t(9;22), t(8;14), or t(11q23)/MLL and precursor T‐ALL. These data support a possible future application of microarray technology for classification of the acute leukemias. © 2003 Wiley‐Liss, Inc.
More extensive genetic alterations in unmutated than in hypermutated cases of chronic lymphocytic leukemia
Authors: Karhu Ritva , Tobin Gerard , Thunberg Ulf , Vilpo Leena , Sundström Christer , Knuutila Sakari , Rosenquist Richard , Vilpo Juhani
Published: June 2003

B‐cell chronic lymphocytic leukemia (CLL) is not a uniform disease entity; approximately half of the CLL cases have undergone immunoglobulin VH gene hypermutation, whereas the other half display unmutated VH genes. We investigated genome changes in 12 hypermutated cases (M‐CLL) and 22 unmutated cases (UM‐CLL) by use of comparative genomic hybridization, G‐banding, and multicolor fluorescence in situ hybridization (m‐FISH) after optimal mitogen stimulation and FISH analysis of typical CLL aberrations: 11q deletion, 13q deletion, and trisomy 12. Very high frequencies of aberrations were found in both groups: 82% in UM‐CLL and 83% in M‐CLL. Deletions of 11q and 13q were equally distributed in M‐CLL and UM‐CLL. However, larger aberrations detectable by CGH, trisomy 12, and complex aberrations were less frequent in M‐CLL than in UM‐CLL. These observations led to a hypothesis that unmutated and mutated CLL have different biological Backgrounds, given that large and/or complex chromosomal aberrations and hypermutation of the CLL progenitor cells tend to be mutually exclusive. © 2003 Wiley‐Liss, Inc.
Monochromosome transfer provides functional evidence for growth‐suppressive genes on chromosome 14 in nasopharyngeal carcinoma
Authors: Cheng Yue , Ko Josephine M. Y. , Lung Hong L. , Lo Paulisally H. Y. , Stanbridge Eric J. , Lung Maria L.
Published: June 2003

In many cancers, including nasopharyngeal carcinoma (NPC), extensive and multiple regions of allelic loss occur on chromosome 14. However, to date no functionally conclusive tumor suppressor genes have yet been identified on this chromosome. Through use of the monochromosome transfer technique, this study provides functional evidence for the importance of two discrete regions of chromosome 14. A newly established A9 mouse donor cell line containing an intact copy of chromosome 14 was used for transfer of this intact chromosome into the NPC HONE1 cell line. Twelve independently established microcell hybrids demonstrated uniform loss of specific chromosome 14 loci from both endogenous and exogenous alleles. By microsatellite typing and fluorescence in situ hybridization with BAC probes, the two critical regions were localized to 14q11.2–13.1 and 14q32.1. Selective elimination of these regions during hybrid selection was strongly associated with both hybrid survival and tumor growth in vivo. This functional evidence now narrows down the candidate areas for further studies and suggests that at least two hitherto unidentified growth‐related genes localized on two critical regions of chromosome arm 14q play an important role in tumorigenesis. © 2003 Wiley‐Liss, Inc.
A new chromosome banding technique, spectral color banding (SCAN), for full characterization of chromosomal abnormalities
Authors: Kakazu Naoki , Bar‐Am Irit , Hada Satoshi , Ago Hiroatsu , Abe Tatsuo
Published: June 2003

We have developed spectral color banding (SCAN) as a new chromosome banding technique based on spectral analysis of differentially labeled chromosome band‐specific painting probes. In this study, we succeeded in displaying a multicolor banding pattern for chromosome 3, which was almost identical to the pattern obtained with the corresponding G‐banding. We applied this method to metaphase cells from different normal male donors with various levels of G‐banding resolution, ranging from 250 to 850 bands per haploid set. The same multicolor banding pattern was observed in all samples regardless of the length of the chromosomes or the quality of the G‐banding. We then used SCAN in a diffuse large B‐cell lymphoma case for a complete analysis of the intrachromosomal change for chromosome 3, which could not be fully characterized by G‐banding or even by spectral karyotyping (SKY). SCAN could detect the duplicated segment and identify the origin of the chromosome band on the basis of the specific spectral color of each band. This study demonstrates that SCAN is a useful tool for full characterization of chromosomal abnormalities not identified by SKY. © 2003 Wiley‐Liss, Inc.
Globalization, global health, and access to healthcare
Authors: Collins Téa
Published: June 2003

It is now commonly realized that the globalization of the world economy is shaping the patterns of global health, and that associated morbidity and mortality is affecting countries' ability to achieve economic growth. The globalization of public health has important implications for access to essential healthcare. The rise of inequalities among and within countries negatively affects access to healthcare. Poor people use healthcare services less frequently when sick than do the rich. The negative impact of globalization on access to healthcare is particularly well demonstrated in countries of transitional economies. No longer protected by a centralized health sector that provided free universal access to services for everyone, large segments of the populations in the transition period found themselves denied even the most basic medical services. Only countries where regulatory institutions are strong, domestic markets are competitive and social safety nets are in place, have a good chance to enjoy the health benefits of globalization. Copyright © 2003 John Wiley & Sons, Ltd.
Prioritization of prevention activities to combat the spread of HIV/AIDS in resource constrained settings: a cost‐effectiveness analysis from Chad, Central Africa
Authors: Hutton Guy , Wyss Kaspar , N'Diékhor Yemadji
Published: June 2003

In Chad, as in most sub‐Saharan Africa countries, HIV/AIDS poses a massive public health threat as well as an economic burden, with prevalence rates estimated at 9% of the adult population. In defining and readjusting the scope and content of the national HIV/AIDS control activities, policy makers sought to identify the most cost‐effective options for HIV/AIDS control. The cost‐effectiveness analysis reported in this paper uses a mixture of local and international information sources combined with appropriate assumptions to model the cost‐effectiveness of feasible HIV prevention options in Chad, with estimates of the budget impact. The most cost‐effective options at under US$100 per infection prevented were peer group education of sex workers and screening of blood donors to identify infected blood before transfusion. These options were followed by mass media and peer group education of high risk men and young people, at around US$500 per infection prevented. Anti‐retroviral therapy for HIV infected pregnant women and voluntary counselling and testing were in the order of US$1000 per infection prevented. The paper concludes with recommendations for which activities should be given priority in the next phase of the national HIV/AIDS control programme in Chad. Copyright © 2003 John Wiley & Sons, Ltd.
Alterations of BLU, a candidate tumor suppressor gene on chromosome 3p21.3, in human nasopharyngeal carcinoma
Authors: Liu Xiao‐Qiong , Chen Han‐Kui , Zhang Xiao‐Shi , Pan Zhi‐Gang , Li Ang , Feng Qi‐Sheng , Long Qing‐Xin , Wang Xun‐Zhang , Zeng Yi‐Xin
Published: June 2003

Nonrandom allelic loss on chromosome 3p is a common event in nasopharyngeal carcinoma (NPC) with the implication that certain tumor suppressor gene(s) in this region are involved in the pathogenesis of these tumors. The BLU gene, located at 3p21.3, has recently been identified as a candidate tumor suppressor gene due to the occurrence of missense mutations and loss of its expression in lung cancer. To investigate the involvement of BLU gene in NPC, we examined both genetic and epigenetic changes of BLU in NPC primary tumors and cell lines. No pathogenic mutations were detected in the entire coding region of this gene in 45 primary NPC tumors and 5 NPC cell lines. While BLU was expressed in 100% (15 of 15) of noncancerous nasopharyngeal epithelia, its transcripts were missing in all 5 NPC cell lines, and absent or reduced mRNA levels were observed in 78% (28 of 36) of the primary tumors. In the NPC cell lines, loss of BLU expression correlated with hypermethylation of the CpG island promoter sequence, and expression was restored after treatment with 5′‐aza‐2′‐deoxycytidine. Methylation specific PCR analysis revealed that the BLU promoter was highly methylated in 74% (17 of 23) of primary tumors in which BLU was downregulated, whereas only 2 of 9 non‐neoplastic nasopharyngeal epithelia exhibited hypermethylation in the BLU promoter region. The high incidence of BLU alterations suggests that it may be one of the critical tumor suppressor genes on chromosome 3p21.3 involved in the development of NPC. © 2003 Wiley‐Liss, Inc.
Endogenous decoy receptor 3 blocks the growth inhibition signals mediated by Fas ligand in human pancreatic adenocarcinoma
Authors: Tsuji Shoichiro , Hosotani Ryo , Yonehara Shin , Masui Toshihiko , Tulachan Sidhartha S. , Nakajima Sanae , Kobayashi Hiroyuki , Koizumi Masayuki , Toyoda Eiji , Ito Daisuke , Kami Kazuhiro , Mori Tomohiko , Fujimoto Koji , Doi Ryuichiro , Imamura Masayuki
Published: June 2003

Many cancers are resistant to Fas‐mediated apoptosis despite the expression of Fas. To investigate the mechanisms by which Fas signals are attenuated, we focused on decoy receptor 3 (DcR3). DcR3 is a soluble receptor against Fas ligand belonging to the tumor necrosis factor receptor superfamily and overexpresses in some forms of cancers. Exogenous DcR3 inhibits Fas‐mediated apoptosis in Fas‐sensitive Jurkat cells. In our study, we examined the expression and function of DcR3 in pancreatic cancers. TaqMan RT‐PCR showed that DcR3 mRNA was highly expressed in pancreatic cancer cell lines (71%) and tissues (67%). Its expression significantly correlated with cancer invasion to veins. Western blotting showed that the DcR3 protein was produced and secreted in 4 of 6 cell lines. The protein expressions were compatible with the mRNA expression. Five of 7 pancreatic cancer cell lines became sensitive to agonistic anti‐Fas antibody (CH‐11) to various extents, without Fas upregulation, when exposed to CH‐11 for 48 hr after pretreatment with IFNγ. Four of 7 pancreatic cancer cell lines were inhibited from growing, compared to control cells, when cocultured with membrane‐bounded Fas ligand (mFasL) transfected lymphomas for 48 hr after pretreatment with IFNγ. DcR3 reduced this growth inhibition when added exogenously. Regression analysis showed that the DcR3 expression significantly correlated with the sensitivity to mFasL, and not to CH‐11. These results suggest that DcR3 is highly expressed in many pancreatic cancers and endogenous DcR3 blocks the growth inhibition signals mediated by mFasL. DcR3 can be a candidate target molecule for the therapeutic intervention. © 2003 Wiley‐Liss, Inc.
Synergistic antiproliferative and apoptotic effects induced by epidermal growth factor receptor and protein kinase a inhibitors in human prostatic cancer cell lines
Authors: Mimeault Murielle , Pommery Nicole , Hénichart Jean‐Pierre
Published: June 2003

Our results revealed that the blockade of epidermal growth factor receptor (EGFR) tyrosine kinase and protein kinase A (PKA) signaling pathways by specific inhibitors (PD153035 and Rp‐cAMPs) leads to a synergistic inhibition of EGF‐ and serum‐stimulated growth of human prostatic cancer cells (LNCaP, DU145 and PC3) concomitant with an arrest in the G1 phase of cellular cycle. Of particular interest, the combination of PD153035 and Rp‐cAMPs also caused a more substantial apoptotic/necrotic death of these prostatic cancer cells as compared to drugs alone. Moreover, we observed that the inhibition of acidic sphingomyelinase and caspase cascades results in a marked reduction of DNA fragmentation and apoptotic death induced by PD153035, alone or in combination with Rp‐cAMPs, in EGF stimulated PC3 cells. This suggests that these agents might mediate their cytotoxic effects at least in part via the ceramide generation and activation of caspase signaling pathways. N‐oleoylethanolamine (OE), an inhibitor of acidic ceramidase, consistently potentiated the apoptotic effects of PD153035 in all the prostatic cancer cell lines tested. Additionally, the cellular ceramide content estimated for PC3 cells was increased after treatment with PD153035, alone or in combination, at a lower dose with OE and Rp‐cAMPs.The synergistic apoptotic effect of PD153035 plus Rp‐cAMPs induced in PC3 was also accompanied by a significant rate of mitochondrial membrane depolarization and release of cytochrome c into cytosol as compared to drugs alone. Combined, the results indicated that the simultaneous inhibition of EGFR and PKA signaling cascades might lead to a more massive apoptotic death of metastatic prostatic cancer cells by increasing ceramide accumulation and activating of caspase cascade of a mitochondrial dependent manner. © 2003 Wiley‐Liss, Inc.
Breast cell invasive potential relates to the myoepithelial phenotype
Authors: Gordon Linda A. , Mulligan Kellie T. , Maxwell‐Jones Helen , Adams Matthew , Walker Rosemary A. , Jones J. Louise
Published: June 2003

On the basis of marker profile, the majority of breast carcinomas are thought to be derived from luminal epithelial cells; however, a subgroup of tumours with more mesenchymal characteristics are associated with a worse prognosis. The hypothesis of our study is that some breast carcinomas exhibit myoepithelial rather than pure mesenchymal differentiation and that acquisition of myoepithelial characteristics confers an aggressive phenotype. Pure luminal epithelial cells and fibroblasts are readily distinguished by many markers but distinguishing between myoepithelial and fibroblast cell lineages is more problematic. The markers found to be most discriminating in our study were CK14, α6β4 integrin and the myoepithelial‐associated desmosomal cadherin DSg3. These markers were applied to a series of breast cell lines and purified normal breast cell populations and the expression profile related to in vitro invasive behaviour. This demonstrated that expression of one or more myoepithelial markers by tumour cells (MDA MB 231, MDA MB 468, MDA MB 436) was associated with a high invasive capacity compared with cells with a pure luminal phenotype (MCF‐7, T47D, ZR75). To address why myoepithelial characteristics are associated with higher invasion, the in vitro behaviour of normal myoepithelial cells and two other nontumourigenic breast cell lines (MCF‐10A, HBL100) was also analysed. Primary myoepithelial cells from normal human breast exhibit a high invasive capacity when grown at low density, suggesting that invasive capacity is part of the myoepithelial phenotype. In keeping with this, both nontumourigenic cell lines exhibited features of the myoepithelial phenotype and a high invasive capacity. These results suggest that tumours that exhibit a myoepithelial phenotype may be clinically more aggressive because a high invasive capacity is intrinsic to the myoepithelial phenotype. © 2003 Wiley‐Liss, Inc.
Distinct methylation profiles of glioma subtypes
Authors: Uhlmann Karen , Rohde Klaus , Zeller Constanze , Szymas Janusz , Vogel Siegfried , Marczinek Karola , Thiel Gundula , Nürnberg Peter , Laird Peter W.
Published: June 2003

Gliomas are tumors of the central nervous system with a wide spectrum of different tumor types. They range from pilocytic astrocytoma, with a generally good prognosis, to the extremely aggressive malignant glioblastoma. In addition to these 2 types of contrasting neoplasms, several other subtypes can be distinguished, each characterized by specific phenotypic, as well as genotypic features. Recently, the epigenotype, as evident from differentially methylated DNA loci, has been proposed to be useful as a further criterion to distinguish between tumor types. In our study, we screened 139 tissue samples, including 33 pilocytic astrocytomas, 46 astrocytomas of different grades, 7 oligoastrocytomas, 10 oligodendrogliomas, 10 glioblastoma multiforme samples and 33 control tissues, for methylation at CpG islands of 15 different gene loci. We used the semiquantitative high throughput method MethyLight to analyze a gene panel comprising ARF, CDKN2B, RB1, APC, CDH1, ESR1, GSTP1, TGFBR2, THBS1, TIMP3, PTGS2, CTNNB1, CALCA, MYOD1 and HIC1. Seven of these loci showed tumor specific methylation changes. We found tissue as well as grade specific methylation profiles. Interestingly, pilocytic astrocytomas showed no evidence of CpG island hypermethylation, but were significantly hypomethylated, relative to control tissues, at MYOD1. Our results show that glioma subtypes have characteristic methylation profiles and, with the exception of pilocytic astrocytomas, show both locus specific hyper‐ as well as hypomethylation. © 2003 Wiley‐Liss, Inc.
Mammary tumor latency is increased in mice lacking the inducible nitric oxide synthase
Authors: Ellies Lesley G. , Fishman Michael , Hardison Joy , Kleeman Jeanine , Maglione Jeannie E. , Manner Cathyryne K. , Cardiff Robert D. , MacLeod Carol L.
Published: June 2003

Nitric oxide (NO) and its metabolites are implicated in carcinogenesis and metastasis. Both stimulatory and inhibitory effects of NO have been reported in relation to breast cancer and its role in the development of malignancies and metastasis remains uncertain. We have used the polyomavirus middle T antigen (PyV‐mT) targeted to the mouse mammary gland and bred into an inducible NO synthase (iNOS)‐deficient C57Bl/6 strain to examine a role for nitric oxide in modulating tumors that develop in the complex environment of the whole animal. The development of hyperplasias was delayed to the extent that the earliest palpable tumors arose 2–4 weeks later in PyV‐mT/iNOS−/− mice compared with PyV‐mT/iNOS+/+ mice, identifying a role for iNOS in early events in mammary tumor formation. Tumors that did develop in PyV‐mT/iNOS−/− mice were characteristically well differentiated and had a cribriform pattern. Other tumors were myoepithelial adenocarcinomas with uniform nuclear size. In contrast, mice capable of iNOS activity typically developed solid nodular adenocarcinomas with a high mitotic index and pleomorphic nuclei. No significant effect of iNOS deficiency was found on vascular density in hyperplasias or tumors by examining CD31‐positive vessels. The infiltration of lesions by macrophages, cells capable of significant NO production, remained unchanged in PyV‐mT/iNOS−/− mice. Metastatic potential was retained by PyV‐mT‐transformed epithelium in the absence of iNOS, indicating that NO production by iNOS is not essential for this process. These results indicate a role for iNOS in tumorigenesis, particularly in the regulation of early events. © 2003 Wiley‐Liss, Inc.
Prognostic value of bcl‐6, CD10 and CD38 immunoreactivity in stage I–II gastric lymphomas: Identification of a subset of CD10+ large B‐cell lymphomas with a favorable outcome
Authors: Ponzoni Maurilio , Ferreri Andrés J.M. , Pruneri Giancarlo , Pozzi Barbara , Dell'Oro Stefania , Pigni Alessandra , Pinotti Graziella , Villa Eugenio , Freschi Massimo , Viale Giuseppe , Capella Carlo
Published: June 2003

bcl‐6, CD10 and CD38 are useful markers for identifying 2 molecularly and prognostically distinct profiles of diffuse large B‐cell lymphomas (LCLs), defined as germinal‐center B‐like and activated B‐like. We investigated the prognostic role of bcl‐6, CD10 and CD38 immunoreactivity in 102 gastrectomized patients with primary gastric lymphomas (PGLs). There were 41 low‐grade marginal zone lymphomas of MALT‐type (LGML) and 61 diffuse large B‐cell lymphomas with (DLCLMLs; n = 31) or without (DLCLs; n = 30) an LGML component. bcl‐6, CD10 and CD38 were significantly more commonly expressed in DLCL or DLCML as compared with LGML (50% vs. 48% vs. 17%, p = 0.0002 for bcl‐6; 27% vs. 26% vs. 0%, p = 0.0004 for CD10; 45% vs. 48% vs. 13%, p = 0.0005 for CD38, respectively). CD10 immunoreactivity was independently associated with a better survival in diffuse LCL patients (5‐year overall survival: 88% ± 8% vs. 66% ± 7%; p = 0.04); bcl‐6 or CD38 immunoreactivities did not disclose any prognostic implication. Age, presence of LGML component, lactic dehydrogenase serum levels and use of chemotherapy were additional independent prognostic factors. We conclude that CD10 immunoreactivity assessment could be a clear, easy‐to‐interpret and reliable prognostic factor in PGL. Accordingly, patients with CD10+ gastric large B‐cell lymphomas may be at reduced risk and eligible for clinical trials evaluating more conservative therapeutic options. © 2003 Wiley‐Liss, Inc.
Myeloperoxidase promotor polymorphism and risk of hepatoblastoma
Authors: Pakakasama Samart , Chen Tina T.‐L. , Frawley William , Muller Carolyn , Douglass Edwin C. , Tomlinson Gail E.
Published: June 2003

Myeloperoxidase (MPO) is a major enzyme found in neutrophils. Oxidation by MPO produces free radicals that demonstrate genotoxic properties. A polymorphism (G to A) within the promotor region of the MPO gene reduces transcription and expression. This polymorphism is associated with a protective effect against some cancers in adults including lung cancer. The objective of our study was to investigate the effect of this MPO polymorphism on the risk of hepatoblastoma, the most common cancer of the liver in childhood. By using PCR‐SSCP, we determined the genotype at this polymorphism in 48 cases of Caucasian children with hepatoblastoma and 180 normal controls. Genotypes were confirmed by a second method using Aci I restriction enzyme restriction. We found that A allele was associated with reduced risk of hepatoblastoma of 50% (OR, 0.51; 95%CI, 0.27–0.93) and G/A or A/A genotype reduced the risk by 56% (OR, 0.44; 95%CI, 0.21–0.90). Our data suggest that A allele is a protective factor with regard to the risk of hepatoblastoma, perhaps by altering genotoxic properties of xenobiotic substances which may act as carcinogens. © 2003 Wiley‐Liss, Inc.