bluuebunny/crossref_metadata_2025 huggingface dataset:
Generalization of positive attitude as a function of subgroup and superordinate group identifications in intergroup contact
Authors: González Roberto , Brown Rupert
Published: March 2003

The role of category salience in mediating the effects of intergroup contact was examined. One theoretical model proposes that some psychological salience of subgroup categories is necessary to facilitate the generalization of attitude change beyond the immediate contact situation. Another argues that a re‐categorization of the subgroups into a new superordinate category is more beneficial, whilst a third suggests that de‐categorizing the situation entirely is optimal. An alternative view, which combines the first two models, proposes a Dual Identity strategy (simultaneous high superordinate and high subgroup categorization) as an important mediator of the relationship between contact variables and intergroup attitudes. In the study, participants (N = 114) undertook a cooperative intergroup task under four conditions of category salience: ‘subgroup’, ‘superordinate’, ‘superordinate and subgroup’, and ‘no group salience’. Evaluative ratings and symbolic reward allocations both for the groups encountered (contact) and those outside the situation (generalization) provided measures of intergroup bias. Bias within the contact situation was mainly eliminated in all conditions. However, on the more generalized bias measures, only the ‘superordinate’ and ‘superordinate and subgroup’ (Dual Identity strategy) conditions maintained this low level; in the other two conditions intergroup bias resurfaced. A combination of the first two models is proposed. Copyright © 2002 John Wiley & Sons, Ltd.
Mechanism of action of quaternary diamino quenchers in capillary zone electrophoresis
Authors: Verzola Barbara , Sebastiano Roberto , Righetti Pier Giorgio , Gelfi Cecilia , Lapadula Marta , Citterio Attilio
Published: March 2003

The synthesis of two novel amino compounds, able to quench and reverse the electroosmotic low (EOF) in capillary electrophoresis is here reported. These chemicals are derivatives of two previously described quaternarized piperazines, 1‐(4‐iodobutyl)‐1,4‐dimethylpiperazin‐1‐ium iodide (M1C4I) and 1‐(4‐iodobutyl)4‐aza‐1‐azoniabicyclo[2.2.2] octane iodide (M7C4I), believed to bind covalently to the silica surface via alkylation of ionized silanols through their terminal, reactive iodine. The novel compounds, although unable to form a covalent bond, due to lack of the o‐butyl iodine, are found to be very efficient in suppressing protein interaction with the wall and reversing the EOF. On the basis of their behavior in solution, the minimal structural motifs for strong binding of amino compounds to the silica wall have been derived and are thought to be: (i) the presence of two quaternary nitrogens in the molecule; (ii) a correct distance between said charged nitrogens, represented by a butyl chain (C4); (iii) an hydrophobic “decoration” of the molecules, consisting on a high CH2/N ratio (in the present case 8:1).
A new integrated statistical approach to the diagnostic use of two‐dimensional maps
Authors: Marengo Emilio , Robotti Elisa , Gianotti Valentina , Righetti Pier Giorgio , Cecconi Daniela , Domenici Enrico
Published: March 2003

Two‐dimensional (2‐D) electrophoresis is a very useful technique for the analysis of proteins in biological tissues. The complexity of the 2‐D maps obtained causes many difficulties in the comparison of different samples. A new method is proposed for comparing different 2‐D maps, based on five steps: (i) the digitalisation of the image; (ii) the transformation of the digitalised map in a fuzzy entity, in order to consider the variability of the 2‐D electrophoretic separation; (iii) the calculation of a similarity index for each pair of maps; (iv) the analysis by multidimensional scaling of the previously obtained similarity matrix; (v) the analysis by classification or cluster analysis techniques of the resulting map co‐ordinates. The method adopted was first tested on some simulated samples in order to evaluate its sensitivity to small changes in the spots position and size. The optimal setting of the method parameters was also investigated. Finally, the method was successfully applied to a series of real samples corresponding to the electrophoretic bidimensional analysis of sera from normal and nicotine‐treated rats. Multidimensional scaling allowed the separation of the two classes of samples without any misclassification.
Proteome analysis using isoelectric focusing in immobilized pH gradient gels followed by mass spectrometry
Authors: Giorgianni Francesco , Desiderio Dominic M. , Beranova‐Giorgianni Sarka
Published: March 2003

Over the past several years, a large effort has been focused on improvements of two‐dimensional (2‐D) gel electrophoresis‐based proteomics technology, and on development of novel approaches for proteome analysis. Here, we describe the application of an alternative strategy for the analysis of complex proteomes. The strategy combines isoelectric focusing in immobilized pH gradient strips (in‐gel IEF), mass spectrometry (MS), and bioinformatics. A protein mixture is separated by in‐gel IEF, and the entire strip is cut into a set of gel sections. Proteins in each gel section are digested with trypsin, and the tryptic peptides are subjected to liquid chromatography‐nanoelectrospray‐quadrupole ion‐trap tandem mass spectrometry (LC‐ESI‐MS/MS). The LC‐ESI‐MS/MS data are used to identify the proteins through searches of a protein sequence database. Using this in‐gel IEF‐LC‐MS/MS strategy, we have identified 127 proteins from a human pituitary. This study demonstrates the potential of the in‐gel IEF‐LC‐MS/MS approach for analyses of complex mammalian proteomes.
Two‐dimensional protein map of human vastus lateralis muscle
Authors: Gelfi Cecilia , De Palma Sara , Cerretelli Paolo , Begum Shagn , Wait Robin
Published: March 2003

Protein samples of human vastus lateralis muscle were analyzed by two‐dimensional gel electrophoresis, using immobilized pH gradients encompassing several pH regions in the first dimension and sodium dodecyl sulfate‐polyacrylamide gel electrophoresis in the second dimension. More than 500 protein spots on each gel were detected by silver staining, of which 150 were excised, digested in‐gel with trypsin and characterized by matrix assisted laser desorptioin/ionization‐mass spectrometry and tandem electrospray mass spectrometry. Using these techniques, 124 spots including contractile proteins and metabolic enzymes were identified. This database should provide a valuable resource for the definition of the functional properties of muscle fibres and for assessment of the influence of e.g., hypoxia, ischaemia and ageing on protein level.
Microchannel wall coatings for protein separations by capillary and chip electrophoresis
Authors: Doherty Erin A. S. , Meagher Robert J. , Albarghouthi Methal N. , Barron Annelise E.
Published: March 2003

The necessity for microchannel wall coatings in capillary and chip‐based electrophoretic analysis of biomolecules is well understood. The regulation or elimination of EOF and the prevention of analyte adsorption is essential for the rapid, efficient separation of proteins and DNA within microchannels. Microchannel wall coatings and other wall modifications are especially critical for protein separations, both in fused‐silica capillaries, and in glass or polymeric microfluidic devices. In this review, we present a discussion of recent advances in microchannel wall coatings of three major classes – covalently linked polymeric coatings, physically adsorbed polymeric coatings, and small molecule additives. We also briefly review modifications useful for polymeric microfluidic devices. Within each category of wall coatings, we discuss those used to eliminate EOF, to tune EOF, to prevent analyte adsorption, or to perform multiple functions. The knowledgeable application of the most promising recent developments in this area will allow for the separation of complex protein mixtures and for the development of novel microchannel wall modifications.
Micropreparative capillary gel electrophoresis of DNA: Rapid expressed sequence tag library construction
Authors: Shi Liang , Khandurina Julia , Ronai Zsolt , Li Bi‐Yu , Kwan Wai King , Wang Xun , Guttman András
Published: March 2003

A capillary gel electrophoresis based automated DNA fraction collection technique was developed to support a novel DNA fragment‐pooling strategy for expressed sequence tag (EST) library construction. The cDNA population is first cleaved by BsaJ I and EcoR I restriction enzymes, and then subpooled by selective ligation with specific adapters followed by polymerase chain reaction (PCR) amplification and labeling. Combination of this cDNA fingerprinting method with high‐resolution capillary gel electrophoresis separation and precise fractionation of individual cDNA transcript representatives avoids redundant fragment selection and concomitant repetitive sequencing of abundant transcripts. Using a computer‐controlled capillary electrophoresis device the transcript representatives were separated by their size and fractions were automatically collected in every 30 s into 96‐well plates. The high resolving power of the sieving matrix ensured sequencing grade separation of the DNA fragments (i.e., single‐base resolution) and successful fraction collection. Performance and precision of the fraction collection procedure was validated by PCR amplification of the collected DNA fragments followed by capillary electrophoresis analysis for size and purity verification. The collected and PCR‐amplified transcript representatives, ranging up to several hundred base pairs, were then sequenced to create an EST library.
Transcription factor binding study by capillary zone electrophoretic mobility shift assay
Authors: Ronai Zsolt , Wang Yan , Khandurina Julia , Budworth Paul , Sasvari‐Szekely Maria , Wang Xun , Guttman András
Published: March 2003

Regulation of gene expression through interaction of proteins with specific DNA sequences is a central issue in functional genomics. Capillary electrophoretic mobility shift assay is an efficient novel method for the investigation of sequence specific protein‐DNA interactions, allowing rapid and sensitive quantification of the complex formation. In this paper, we present a pilot study on capillary zone electrophoretic mobility shift assay (CZEMSA) to investigate the interaction between the transcription factors of HeLa nuclear extract and Sp1‐specific fluorescein‐labeled oligonucleotide, using the unlabeled probe as competitor. The mobility shift assay was accomplished by CZE in coated capillaries without polymeric buffer additives. Specificity of the DNA protein complex formation was verified by competition experiments, as well as by supershift assay with an anti‐Sp1 antibody. The applied electric field strength did not affect the stability of DNA‐protein complex during the electrophoretic analysis, allowing rapid identification and quantification of the protein DNA interaction. A practical application to study the interaction between Oryza sativa MADS‐box transcription factor 4 (OsMADS4) and its consensus sequence is also reported.
Separation of peptides and proteins by capillary electrophoresis using acidic buffers containing tetraalkylammonium cations and cyclodextrins
Authors: Quang Changyu , Malek Amir , Khaledi Morteza G.
Published: March 2003

A method for improving separations of peptides and other positively charged species in capillary zone electrophoresis with untreated capillaries using acidic buffers containing tetraalkylammonium cations is described. Tetramethylammonium and tetrabutylammonium cations dynamically modify the capillary surface, leading to a reversal in the direction of the electroosmotic flow. As a result, the adsorption of positively charged peptides and proteins is minimized, and resolution and peak capacity are improved as the migration of cationic analytes is counterbalanced by the electroosmotic flow. The combining effect of reversing electroosmotic flow and cyclodextrin inclusion complexation on separations of closely related peptides and a protein mixture, as well as tryptic digest of hemoglobin is demonstrated.
Attomole sensitivity for unlabeled proteins and polypeptides with on‐chip capillary electrophoresis and universal detection by interferometric backscatter
Authors: Wang Zhanling , Swinney Kelly , Bornhop Darryl J.
Published: March 2003

A universal detector based on backscatter interferometry has been developed to perform nanoliter volume refractive index measurements for on‐chip sodium dodecyl sulfate (SDS) gel based (polyethylene oxide gel) separations and quantification label‐free proteins. The on‐chip interferometric backscatter detector (OCIBD) system consists of a simple, folded optical train based on the interaction of a laser beam with an etched channel in the shape of half cylinder in a fused‐silica plate. The backscattered light from the channel takes on the form of a high‐contrast interference pattern that contains information related to the bulk properties of the fluid located within the probe or detection volume of 2.32×10−9 L. Depending on capillary electrophoresis (CE) injection method, the positional changes of the interference pattern extrema (fringes) allow for the quantification of unlabeled proteins at levels ranging from 11 to 310 amol (2.7×10−8 mol/L) with a linear dynamic range of 2.5 decades (egg albumin). Using OCIBD microchannel‐based SDS capillary gel electrophoresis (SDS/CGE), separation and detection of five label‐free proteins was achieved in less than 100 seconds with detection limits ranging from 0.95 pg (1.1×10−16 mol or 2.5×10−7 mol/L) of calmodulin to 7.0 pg (1.0×10−16 mol or 2.4×10−7 mol/L) for bovine serum albumin (BSA) without signal filtering or active thermal control. This development shows that a universal detector based on backscatter interferometry can be used effectively for on‐chip label‐free solute analysis.
Capillary electrophoresis coupled to time of flight‐mass spectrometry of therapeutic peptide hormones
Authors: Sanz‐Nebot Victoria , Benavente Fernando , Balaguer Elvira , Barbosa José
Published: March 2003

We have established a method for separation and characterization of a series of peptide hormones of pharmaceutical interest and wide therapeutical use by capillary electrophoresis‐electrospray‐mass spectrometry (CE‐ES‐MS) using a sheath flow interface. Several parameters were systematically investigated, such as concentration of the electrolyte, organic solvent and sheath liquid composition, gas flow rates and capillary position. Moreover, limits of detection, linearity, repeatability and day‐to‐day reproducibility of the proposed method were studied in order to obtain the main quality parameters.
Analysis of the performance of antibody capture methods using fluorescent peptides with capillary zone electrophoresis with laser‐induced fluorescence
Authors: Jackman Roy , Schmerr Mary Jo
Published: March 2003

A method to analyze the performance of an antibody capture method using fluorescent peptides by capillary zone electrophoresis using laser‐induced fluorescence (CZE‐LIF) for detection has been developed. Fluorescent peptides from the prion protein were synthesized and the corresponding antibodies were produced in rabbits against these peptides. The antibodies were used to capture the fluorescent peptides. The antibodies were then bound to protein A Sepharose. After elution, the amount of fluorescent peptide that was captured vs. the total amount placed in the assay was evaluated by CZE‐LIF. Of the three peptides used in this evaluation, it was found that the recovery was approximately 25–35%. When the abnormal prion protein was prepared from scrapie‐infected brain samples from hamsters and a sheep using the previously described extraction method and this method, the amount of abnormal prion protein that was measured in the fluorescence immunoassay correlated with amounts estimated from Western blot. We conclude that this method can be used to detect abnormal prion protein in a tissue sample.
Asymmetric one‐storey elastic systems with non‐linear viscous and viscoelastic dampers: Earthquake response
Authors: Lin Wen‐Hsiung , Chopra Anil K.
Published: March 2003

Investigated are earthquake responses of one‐way symmetric‐plan, one‐storey systems with non‐linear fluid viscous dampers (FVDs) attached in series to a linear brace (i.e. Chevron or inverted V‐shape braces).Thus, the non‐linear damper is viscous when the brace is considered rigid or viscoelastic (VE) when the brace is flexible. The energy dissipation capacity of a non‐linear FVD is characterized by an amplitude‐dependent damping ratio for an energy‐equivalent linear FVD, which is determined assuming the damper undergoes harmonic motion. Although this formulation is shown to be advantageous for single‐degree‐of‐freedom (SDF) systems, it is difficult to extend its application to multi‐degree‐of‐freedom (MDF) systems for two reasons: (1) the assumption that dampers undergo harmonic motion in parameterizing the non‐linear damper is not valid for its earthquake‐induced motion of an MDF system; and (2) ensuring simultaneous convergence of all unknown amplitudes of dampers is difficult in an iterative solution of the non‐linear system. To date, these limitations have precluded the parametric study of the dynamics of MDF systems with non‐linear viscous or VE dampers. However, they are overcome in this investigation using concepts of modal analysis because the system is weakly non‐linear due to supplemental damping. It is found that structural response is only weakly affected by damper non‐linearity and is increased by a small amount due to bracing flexibility. Thus, the effectiveness of supplemental damping in reducing structural responses and its dependence on the planwise distribution of non‐linear VE dampers were found to be similar to that of linear FVDs documented elsewhere. As expected, non‐linear viscous and VE dampers achieve essentially the same reduction in response but with much smaller damper force compared to linear dampers. Finally, the findings in this investigation indicate that the earthquake response of the asymmetric systems with non‐linear viscous or VE dampers can be estimated with sufficient accuracy for design applications by analysing the same asymmetric systems with all non‐linear dampers replaced by energy‐equivalent linear viscous dampers. Copyright © 2003 John Wiley & Sons, Ltd.
Exact computation of input‐energy spectra from Fourier amplitude spectra
Authors: Ordaz Mario , Huerta Benjamin , Reinoso Eduardo
Published: March 2003

A theoretically exact relation is presented between the Fourier amplitude spectrum and the elastic input‐energy spectrum. This energy spectrum is computed from the Fourier acceleration amplitude spectrum and the real part of the relative velocity transfer function of the single‐degree‐of‐freedom elastic oscillator. Some accelerometric records collected worldwide are used to prove the solution. It is shown that the relation presented in this work opens the door for a better understanding of the relationship between the input‐energy spectrum and other seismological variables, such as magnitude and focal distance. Copyright © 2003 John Wiley & Sons, Ltd.
Inelastic dynamic analysis of RC bridges accounting for spatial variability of ground motion, site effects and soil–structure interaction phenomena. Part 1: Methodology and analytical tools
Authors: Sextos Anastasios G. , Pitilakis Kyriazis D. , Kappos Andreas J.
Published: March 2003

During strong ground motion it is expected that extended structures (such as bridges) are subjected to excitation that varies along their longitudinal axis in terms of arrival time, amplitude and frequency content, a fact primarily attributed to the wave passage effect, the loss of coherency and the role of local site conditions. Furthermore, the foundation interacts with the soil and the superstructure, thus significantly affecting the dynamic response of the bridge. A general methodology is therefore set up and implemented into a computer code for deriving sets of appropriately modified time histories and spring–dashpot coefficients at each support of a bridge with account for spatial variability, local site conditions and soil–foundation–superstructure interaction, for the purposes of inelastic dynamic analysis of RC bridges. In order to validate the methodology and code developed, each stage of the proposed procedure is verified using recorded data, finite‐element analyses, alternative computer programs, previous research studies, and closed‐form solutions wherever available. The results establish an adequate degree of confidence in the use of the proposed methodology and code in further parametric analyses and seismic design. Copyright © 2003 John Wiley & Sons, Ltd.
Inelastic dynamic analysis of RC bridges accounting for spatial variability of ground motion, site effects and soil–structure interaction phenomena. Part 2: Parametric study
Authors: Sextos Anastasios G. , Kappos Andreas J. , Pitilakis Kyriazis D.
Published: March 2003

The methodology for dealing with spatial variability of ground motion, site effects and soil–structure interaction phenomena in the context of inelastic dynamic analysis of bridge structures, and the associated analytical tools established and validated in a companion paper are used herein for a detailed parametric analysis, aiming to evaluate the importance of the above effects in seismic design. For a total of 20 bridge structures differing in terms of structural type (fundamental period, symmetry, regularity, abutment conditions, pier‐to‐deck connections), dimensions (span and overall length), and ground motion characteristics (earthquake frequency content and direction of excitation), the dynamic response corresponding to nine levels of increasing analysis complexity was calculated and compared with the ‘standard’ case of a fixed base, uniformly excited, elastic structure for which site effects were totally ignored. It is concluded that the dynamic response of RC bridges is indeed strongly affected by the coupling of the above phenomena that may adversely affect displacements and/or action effects under certain circumstances. Evidence is also presented that some bridge types are relatively more sensitive to the above phenomena, hence a more refined analysis approach should be considered in their case. Copyright @ 2003 John Wiley & Sons, Ltd.
Seismic test of a full‐scale model of a five‐storey stone pagoda
Authors: Kim Jae Kwan , Ryu Hyeuk
Published: March 2003

A moderate size earthquake of magnitude 5 occurred at Whagae‐Myun, Hadong‐Gun, Kyongsangnam‐Do, Korea on 4 July 1936. It caused severe damage to the buildings and other structures in Sang‐Gye‐Sa, a famous and beautiful Buddhist temple. A five‐storey stone pagoda was standing in front of Keumdang, the main building. The top component of the pagoda was tipped over and fell down to the ground during the earthquake. In order to have a quantitative estimate of the intensity of the earthquake, a full‐scale model was constructed through a rigorous verification process. The completed model was mounted on a shaking table and subjected to two kinds of dynamic test: exploratory test and fragility test. The exploratory test was performed with low intensity shaking. In the fragility test, the failure modes of the model were investigated while increasing the shaking intensity. The construction details of the model are described and test procedures are reported. Important relations between failure modes and characteristics of ground motion were obtained from the tests. The intensity of the 1936 earthquake was estimated from the examination of test results. Copyright © 2003 John Wiley & Sons, Ltd.
Close range digital photogrammetric analysis of experimental drainage basin evolution
Authors: Brasington J. , Smart R. M. A.
Published: March 2003

Despite the difficulties of establishing formal hydraulic and geometric similarity, small‐scale models of drainage basins have often been used to investigate the evolution and dynamics of larger‐scale landforms. Historically, this analysis has been restricted to planform basin characteristics and only in the last decade has the topographic similarity of experimental landscapes been explored through explicitly three‐dimensional parameters such as the distributions of cumulative drainage area, area–slope and catchment elevation. The current emphasis on three‐dimensional morphometry reflects a growing awareness of the descriptive paucity of planform data and the need for more robust analysis of spatial scaling relationships. This paradigm shift has been significantly facilitated by technological developments in topographic survey and digital elevation modelling (DEM) which now present the opportunity to acquire and analyse high‐resolution, distributed elevation data. Few studies have, however, attempted to use topographic modelling to provide information on the changing pattern and rate of sediment transport though an evolving landscape directly by using multitemporal DEM differencing techniques. This paper reports a laboratory study in which digital photogrammetry was employed to derive high‐resolution DEMs of a simulated landscape in declining equilibrium at 15 minute frequency through a 240 minute simulation. Detailed evaluation of the DEMs revealed a vertical precision of 1·2 mm and threshold level of change detection between surfaces of ±3 mm at the 95 per cent confidence level. This quality assurance set the limits for determining the volumetric change between surfaces, which was used to recover the sediment budget through the experiment and to examine local ‐ and basin‐scale rates of sediment transport. A comparison of directly observed and morphometric estimates of sediment yield at the basin outlet was used to quantify the closure of the sediment budget over the simulation, and revealed an encouragingly small 6·2 per cent error. The application of this dynamic morphological approach has the potential to offer new insights into the controls on landform development, as demonstrated here by an analysis of the changing pattern of the basin sediment delivery ratio during network growth. Copyright © 2003 John Wiley & Sons, Ltd.
Application of airborne LiDAR in river environments: the River Coquet, Northumberland, UK
Authors: Charlton M. E. , Large A. R. G. , Fuller I. C.
Published: March 2003

The potential offered by LiDAR (laser‐induced direction and ranging) for the mapping of gravel‐bed river environments is addressed in this paper. A LiDAR dataset was obtained for a reach of the River Coquet, Northumberland, UK. Topographic data were acquired from the field at the same time using theodolite‐EDM survey of a number of cross‐profiles across the active river channel and bar units. These cross‐profiles provide a means of comparing measurements from the LiDAR data with ground survey. Ordnance Survey large‐scale mapping was used to georeference the survey data, which were then integrated with the LiDAR dataset using GIS software. A close correspondence between ground survey‐derived cross‐profiles and those generated using LiDAR is observed. However, the presence of both vegetation and deep water introduces anomalies in the LiDAR surface. Correction for these anomalies is needed to improve the accuracy of LiDAR mapping in the UK context and similar river environments. It is concluded that LiDAR has potential as an accurate survey tool for obtaining high resolution topographic data from unvegetated, exposed bar surfaces. Copyright © 2003 John Wiley & Sons, Ltd.
Multicriteria methods for technology foresight
Authors: Salo Ahti , Gustafsson Tommi , Ramanathan Ramakrishnan
Published: March 2003

In recent years, many countries have carried out foresight exercises to better exploit scientific and technological opportunities. Often, these exercises have sought to identify ‘critical’ or ‘key’ technologies or, more broadly, to establish research priorities. In this paper, we consider the potential of multicriteria decision‐making methods in this kind of priority‐determination and examine the limitations of these methods in the foresight context. We also provide results from a combined evaluation and foresight study where multicriteria methods were deployed to support the shaping of research and technology development activities in the Finnish forestry and forest industry. Copyright © 2003 John Wiley & Sons, Ltd.
Detailed gene copy number and RNA expression analysis of the 17q12–23 region in primary breast cancers
Authors: Willis Simon , Hutchins Anne‐Marie , Hammet Fleur , Ciciulla John , Soo Wee‐Kheng , White David , van der Spek Peter , Henderson Michael A. , Gish Kurt , Venter Deon J. , Armes Jane E.
Published: March 2003

Chromosome region 17q12–23 commonly shows an increase in DNA copy number in breast cancers, suggesting that several oncogenes are located at this site. We performed a high‐resolution expression array and comparative genomic hybridization analysis of genes mapped to the entire 17q12–23 region, to identify novel candidate oncogenes. We identified 24 genes that showed significant overexpression in breast cancers with gain of 17q12–23, compared to cancers without gain. These genes included previously identified oncogenes, together with several novel candidate oncogenes. FISH analysis using specific gene probes hybridized to tissue arrays confirmed the underlying amplification of overexpressed genes. This high‐resolution analysis of the 17q12–23 region indicates that several established and novel candidate oncogenes, including a Wnt‐signaling pathway member, are amplified and overexpressed within individual primary breast cancer samples. We were also able to confirm the presence of two apparently separate and reciprocally amplified groups of genes within this region. Investigation of these genes and their functional interactions will facilitate our understanding of breast oncogenesis and optimal management of this disease. © 2003 Wiley‐Liss, Inc.
Deletion of Brca2 exon 27 causes hypersensitivity to DNA crosslinks, chromosomal instability, and reduced life span in mice
Authors: Donoho Greg , Brenneman Mark A. , Cui Tracy X. , Donoviel Dorit , Vogel Hannes , Goodwin Edwin H. , Chen David J. , Hasty Paul
Published: March 2003

The Brca2 tumor‐suppressor gene contributes to genomic stability, at least in part by a role in homologous recombinational repair. BRCA2 protein is presumed to function in homologous recombination through interactions with RAD51. Both exons 11 and 27 of Brca2 code for domains that interact with RAD51; exon 11 encodes eight BRC motifs, whereas exon 27 encodes a single, distinct interaction domain. Deletion of all RAD51‐interacting domains causes embryonic lethality in mice. A less severe phenotype is seen with BRAC2 truncations that preserve some, but not all, of the BRC motifs. These mice can survive beyond weaning, but are runted and infertile, and die very young from cancer. Cells from such mice show hypersensitivity to some genotoxic agents and chromosomal instability. Here, we have analyzed mice and cells with a deletion of only the RAD51‐interacting region encoded by exon 27. Mice homozygous for this mutation (called brca2lex1) have a shorter life span than that of control littermates, possibly because of early onsets of cancer and sepsis. No other phenotype was observed in these animals; therefore, the brca2lex1 mutation is less severe than truncations that delete some BRC motifs. However, at the cellular level, the brca2lex1 mutation causes reduced viability, hypersensitivity to the DNA interstrand crosslinking agent mitomycin C, and gross chromosomal instability, much like more severe truncations. Thus, the extreme carboxy‐terminal region encoded by exon 27 is important for BRCA2 function, probably because it is required for a fully functional interaction between BRCA2 and RAD51. © 2003 Wiley‐Liss, Inc.
Prostate cancer aggressiveness locus on chromosome segment 19q12–q13.1 identified by linkage and allelic imbalance studies
Authors: Neville Phillippa J. , Conti David V. , Krumroy Lisa M. , Catalona William J. , Suarez Brian K. , Witte John S. , Casey Graham
Published: March 2003

Whole‐genome scan studies recently identified a locus on chromosome segments 19q12–q13.11 linked to prostate tumor aggressiveness by use of the Gleason score as a quantitative trait. We have now completed finer‐scale linkage mapping across this region that confirmed and narrowed the candidate region to 2 cM, with a peak between markers D19S875 and D19S433. We also performed allelic imbalance (AI) studies across this region in primary prostate tumors from 52 patients unselected for family history or disease status. A high level of AI was observed, with the highest rates at markers D19S875 (56%) and D19S433 (60%). Furthermore, these two markers defined a smallest common region of AI of 0.8 Mb, with 15 (29%) prostate tumors displaying interstitial AI involving one or both markers. In addition, we noted a positive association between AI at marker D19S875 and extension of tumor beyond the margin (P = 0.02) as well as a higher Gleason score (P = 0.06). These data provide strong evidence that we have mapped a prostate tumor aggressiveness locus to chromosome segments 19q12–q13.11 that may play a role in both familial and non‐familial forms of prostate cancer. © 2003 Wiley‐Liss, Inc.
Analysis of t(9;11) chromosomal breakpoint sequences in childhood acute leukemia: Almost identical MLL breakpoints in therapy‐related AML after treatment without etoposides
Authors: Langer Thorsten , Metzler Markus , Reinhardt Dirk , Viehmann Susanne , Borkhardt Arndt , Reichel Martin , Stanulla Martin , Schrappe Martin , Creutzig Ursula , Ritter Jörg , Leis Thomas , Jacobs Ulla , Harbott Jochen , Beck Jörn D. , Rascher Wolfgang , Repp Reinald
Published: March 2003

The translocation t(9;11)(p22;q23) is a recurring chromosomal abnormality in acute myeloid leukemia (AML) fusing two genes designated as MLL and AF9. Within MLL, almost all rearrangements cluster in an 8.3‐kb restricted region and fuse 5′ portions of MLL to a variety of heterologous genes in various 11q23 translocations. AF9 is one of the most common fusion partners of MLL. It spans more than 100 kb, and two breakpoint cluster regions (BCRs) have been identified in a telomeric region of intron 4 (BCR1) and within introns 7 and 8 (BCR2). We investigated 11 children's bone marrow or peripheral blood samples (3 AML, 5 t‐AML, 2 ALL, 1 ALL relapse) and two cell lines (THP‐1 and Mono‐Mac‐6) with cytogenetically diagnosed translocations t(9;11). By use of an optimized multiplex nested long‐range PCR assay, a breakpoint‐spanning DNA fragment from each sample was amplified and directly sequenced. In four patients and two cell lines, the AF9 breakpoints were located within BCR1 and in two patients within BCR2, respectively. However, in five patients the AF9 breakpoints were found outside the previously described BCRs within the centromeric region of intron 4 and even within intron 3 in one case. All five patients with a secondary AML, who had not received etoposides during treatment of the primary malignant disease, revealed almost identical MLL breakpoints very close to a breakage hot spot inducible by topoisomerase II inhibitors or apoptotic triggers in vitro. Sequence patterns around the breakpoints indicated involvement of a “damage‐repair mechanism” in the development of t(9;11) similar to t(4;11) in infants' acute leukemia. © 2003 Wiley‐Liss, Inc.
Pancreatic carcinoma cell lines with SMAD4 inactivation show distinct expression responses to TGFB1
Authors: Jonson Tord , Heidenblad Markus , Håkansson Petra , Gorunova Ludmila , Johansson Bertil , Fioretos Thoas , Höglund Mattias
Published: March 2003

Transforming growth factor beta‐1 (TGFB1)–induced gene expression was studied in five pancreatic carcinoma cell lines and one known TGFB1‐sensitive cell line (HaCaT) by use of high‐density filter‐based cDNA microarrays representing over 4,000 human genes. The results indicate a complex cellular response to TGFB1 with 10% of the investigated genes showing altered expression after 3 or 48 hr of TGFB1 exposure. The tumor cell lines displayed a gradually inversed gene expression pattern, which correlated with reduced sensitivity to TGFB1, as compared to the HaCaT cell line. In the HaCaT cells, several proapoptotic genes showed increased expression in response to TGFB1, whereas the expression of antiapoptotic genes was decreased. In contrast, two pancreatic carcinoma cell lines, previously found to be growth stimulated by TGFB1, displayed an expression pattern opposite to that of these genes. Similarly, the expression of other functional groups of genes, such as cell cycle and transcription factor related genes, was almost completely reversed in these two tumor cell lines. Importantly, three of the five investigated pancreatic carcinoma cell lines responded to TGFB1, although they had SMAD4 inactivations, suggesting that the observed gene expression changes in these cell lines must be accomplished by SMAD‐independent pathways. © 2003 Wiley‐Liss, Inc.
Insights into biaxial extensional tectonics: an examplefrom the Sandıklı Graben, West Anatolia, Turkey
Authors: Cihan Mustafa , Saraç Gerçek , Gökçe Oktay
Published: March 2003

West Anatolia, together with the Aegean Sea and the easternmost part of Europe, is one of the best examples of continental extensional tectonics. It is a complex area bounded by the Aegean–Cyprus Arc to the south and the North Anatolian Fault Zone (NAFZ) to the north. Within this complex and enigmatic framework, the Sandıklı Graben (10 km wide, 30 km long) has formed at the eastern continuation of the Western Anatolian extensional province at the north‐northwestward edge of the Isparta Angle. Recent studies have suggested that the horst–graben structures in West Anatolia formed in two distinct extensional phases. According to this model the first phase of extension commenced in the Early–Middle Miocene and the last, which is accepted as the onset of neotectonic regime, in Early Pliocene. However, it is controversial whether two‐phase extension was separated by a short period of erosion or compression during Late Miocene–Early Pliocene. Both field observations and kinematic analysis imply that the Sandıklı Graben has existed since the Late Pliocene, with biaxial extension on its margins which does not necessarily indicate rotation of regional stress distribution in time. Although the graben formed later in the neotectonic period, the commencement of extension in the area could be Early Pliocene (c. 5 Ma) following a severe but short time of erosion at the end of Late Miocene. The onset of the extensional regime might be due to the initiation of westward motion of Anatolian Platelet along the NAFZ that could be triggered by the higher rate of subduction at the east Aegean–Cyprus Arc in the south of the Aegean Sea. Copyright © 2003 John Wiley & Sons, Ltd.
White matter tractography using diffusion tensor deflection
Authors: Lazar Mariana , Weinstein David M. , Tsuruda Jay S. , Hasan Khader M. , Arfanakis Konstantinos , Meyerand M. Elizabeth , Badie Benham , Rowley Howard A. , Haughton Victor , Field Aaron , Alexander Andrew L.
Published: March 2003

Diffusion tensor MRI provides unique directional diffusion information that can be used to estimate the patterns of white matter connectivity in the human brain. In this study, the behavior of an algorithm for white matter tractography is examined. The algorithm, called TEND, uses the entire diffusion tensor to deflect the estimated fiber trajectory. Simulations and imaging experiments on in vivo human brains were performed to investigate the behavior of the tractography algorithm. The simulations show that the deflection term is less sensitive than the major eigenvector to image noise. In the human brain imaging experiments, estimated tracts were generated in corpus callosum, corticospinal tract, internal capsule, corona radiata, superior longitudinal fasciculus, inferior longitudinal fasciculus, fronto‐occipital fasciculus, and uncinate fasciculus. This approach is promising for mapping the organizational patterns of white matter in the human brain as well as mapping the relationship between major fiber trajectories and the location and extent of brain lesions. Hum. Brain Mapping 18:306–321, 2003. © 2003 Wiley‐Liss, Inc.
Preferences and person trade‐offs: forcing consistency or inconsistency in health‐related quality of life measures?
Authors: Mansley Edward C. , Elbasha Elamin H.
Published: March 2003

We consider assumptions about preferences implicit in the person trade‐off exercises used to derive health‐related quality of life measures for the Global and US Burden of Disease Projects. Because these methods and their results have the potential of being adopted by other researchers, a critical review of this methodology and its assumptions is warranted. Exercise participants are told that quality of life valuation is approached using two different questions to reveal logical inconsistencies in each person's responses. An inconsistency is claimed to exist if a participant's two responses violate a particular mathematical relationship, and participants are forced to modify their responses to satisfy that relationship. We demonstrate that this supposed ‘logical’ relationship need not hold for logically consistent, rational individuals, and we prove that the relationship will in fact hold only for a particular class of social value functions exhibiting two characteristics that may not be consistent with the preferences of some participants. These results imply that the forced modification may invalidate some responses, as it may require some participants to provide final answers that are inconsistent with their true preferences. We then discuss preference characterizations in the existing person trade‐off literature, from which this relationship may have been derived. Published in 2002 by John Wiley & Sons, Ltd.
The effect of cigarette prices on youth smoking
Authors: Ross Hana , Chaloupka Frank J.
Published: March 2003

Prior economic research provides mixed evidence on the impact of cigarette prices on youth smoking. This paper empirically tests the effects of various price measures on youth demand for cigarettes using data collected in a recent nationally representative survey of 17 287 high school students. In addition to commonly used cigarette price measures, the study also examined the effect of price as perceived by the students. This unique information permits the study of the effect of teen‐specific price on cigarette demand. The analysis employed a two‐part model of cigarette demand based on a model developed by Cragg (1971) in which the propensity to smoke and the intensity of the smoking habit are modeled separately. The results confirm that higher cigarette prices, irrespective of the way they are measured, reduce probability of youth cigarette smoking. There is also some evidence of negative price effect on smoking intensity, but it is sensitive to the price measure used in the model. The largest impact on cigarette demand has the teen‐specific, perceived price of cigarettes. Copyright © 2002 John Wiley & Sons, Ltd.
A note on cost‐value analysis
Authors: Østerdal Lars Peter
Published: March 2003

We discuss ‘cost‐value analysis’, a method for health care resource allocation suggested by Nord et al. (Nord E et al. Incorporating societal concerns for fairness in numerical valuations of health programmes. Health Econ 1999; 8: 25–39). Some difficulties and issues for future research are pointed out. Copyright © 2002 John Wiley & Sons, Ltd.
Distribution of NADPH‐diaphorase and expression of nNOS, N‐methyl‐D‐aspartate receptor (NMDAR1) and non‐NMDA glutamate receptor (GlutR2) genes in the neurons of the hippocampus after domoic acid‐induced lesions in adult rats
Authors: Ananth C. , Dheen S. Thameem , Gopalakrishnakone P. , Kaur C.
Published: March 2003

Neuronal degeneration followed by detection of nitric oxide (NO)‐producing neurons of the hippocampus was investigated at 4 h, 16 h, 24 h, 2 days, 5 days, and 14 days after administration of domoic acid (DA), in the present study. Histopathological analysis (Nissl staining) displayed dark‐stained degenerating neurons in the hippocampus at 24 h to 14 days after DA administration, with degeneration most severe at 5–14 days. NADPH‐d‐positive neurons were observed in different subfields of the hippocampus in control rats and DA treated rats at 4–24 h. Complete loss of NADPH‐d‐positive neurons in the CA1 and CA3 subfields and also in the hilus of dentate gyrus (DG) was observed at 5 days and 14 days after the administration of DA. In contrast, at 4–24 h, neuronal nitric oxide synthase (nNOS)‐immunoreactive cells were absent from the hippocampal subfields in control and DA‐treated animals but were observed at 5 days and 14 days after DA administration. N‐methyl‐D‐aspartate receptor (NMDAR1) immunoreactivity was increased in the hippocampal neurons at 5 days after DA administration and double immunofluorescence demonstrated its coexpression with induced nNOS expression. No significant change could be observed in the immunoreactivity of non‐NMDA receptor (GlutR2) as compared with the controls, while occasional immunoreactive neurons were colocalized with induced nNOS expression. Reverse transcription‐polymerase chain reaction analysis showed the upregulated expression of nNOS and downregulated expression of NMDAR1 at 5 days after the administration of DA. Although nNOS mRNA expression was rapidly induced at 5 days after DA administration, in situ hybridization analysis revealed complete loss of nNOS mRNA expression in the region of neuronal degeneration in the hippocampus at 24 h and 5 days after DA administration. The present study has shown that NADPH‐d and nNOS express differentially in the neurons of the hippocampus in DA‐induced neurotoxicity. It is speculated that induction of nNOS and glutamate receptor genes in the neurons of the hippocampus in response to DA‐induced neurotoxicity could have contributed to the neuronal degeneration. Hippocampus 2003;13:260–272. © 2003 Wiley‐Liss, Inc.
Representation of place by monkey hippocampal neurons in real and virtual translocation
Authors: Hori Etsuro , Tabuchi Eiichi , Matsumura Nobuhisa , Tamura Ryoi , Eifuku Satoshi , Endo Shunro , Nishijo Hisao , Ono Taketoshi
Published: March 2003

The hippocampal formation (HF) is hypothesized as a neuronal substrate of a cognitive map, which represents environmental spatial information by an ensemble of neural activity. However, the relationships between the hippocampal place cells and the cognitive map have not been clarified in monkeys. The present study was designed to investigate how activity patterns of place‐selective neurons encode spatial relationships of various environmental stimuli; to do this, we used multidimensional scaling (MDS) for hippocampal neuronal activity in the monkey during the performance of real and virtual translocation. Of 389 neurons recorded from the monkey HF and parahippocampal gyrus (PH), 166 had place fields that displayed increased activity in a specific area of an experimental field and/or on a monitor (place‐selective neurons). The MDS transformed relationships among the 16 places in the experimental field and the monitor, expressed as correlation coefficients between all possible pairs of two places based on the 166 place‐selective responses, into geometric relationships in a two‐dimensional MDS space. In the real translocation tasks, the 16 places were distributed throughout the MDS space, and their relative positions were well correlated to real positions in the experimental laboratory. However, the correlation between the MDS space and real arrangements was significantly smaller in virtual than real translocation tasks. The present results strongly suggest that activity patterns of the HF and PH neurons represent spatial information and might provide a neurophysiological basis for a cognitive map. Hippocampus 2003;13:190–196. © 2003 Wiley‐Liss, Inc.