bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantitative Performance of E‐Scribe Warehouse in Detecting Quality Issues With Digital Annotated ECG Data From Healthy Subjects
Authors: Sarapa Nenad , Mortara Justin L. , Brown Barry D. , Isola Lamberto , Badilini Fabio
Published: March 2008

The US Food and Drug Administration recommends submission of digital electrocardiograms in the standard HL7 XML format into the electrocardiogram warehouse to support preapproval review of new drug applications. The Food and Drug Administration scrutinizes electrocardiogram quality by viewing the annotated waveforms and scoring electrocardiogram quality by the warehouse algorithms. Part of the Food and Drug Administration warehouse is commercially available to sponsors as the E‐Scribe Warehouse. The authors tested the performance of E‐Scribe Warehouse algorithms by quantifying electrocardiogram acquisition quality, adherence to QT annotation protocol, and T‐wave signal strength in 2 data sets: “reference” (104 digital electrocardiograms from a phase I study with sotalol in 26 healthy subjects with QT annotations by computer‐assisted manual adjustment) and “test” (the same electrocardiograms with an intentionally introduced predefined number of quality issues). The E‐Scribe Warehouse correctly detected differences between the 2 sets expected from the number and pattern of errors in the “test” set (except for 1 subject with QT misannotated in different leads of serial electrocardiograms) and confirmed the absence of differences where none was expected. E‐Scribe Warehouse scores below the threshold value identified individual electrocardiograms with questionable T‐wave signal strength. The E‐Scribe Warehouse showed satisfactory performance in detecting electrocardiogram quality issues that may impair reliability of QTc assessment in clinical trials in healthy subjects.
Using Tax Parcels to Select a Location-Based Sample
Authors: Craun Sarah W. , Freisthler Bridget
Published: March 2008

Social science research is increasingly considering place when examining social programs and policies with a spatial component. A specific research challenge involving spatial policies is how to select a sample of individuals based on their geographic locations. This article illustrates the use of geographic information systems, tax parcels, and mail surveys to target residents in varied geographic areas. A provided example demonstrates how researchers obtained a sample of respondents living within one tenth of a mile of multiple registered sex offenders. The challenges of using tax parcels to obtain addresses for apartments and mobile home parks are also explored.
Do SMEs do Knowledge Management?
Authors: Hutchinson Vicky , Quintas Paul
Published: March 2008

Recent studies of knowledge management indicate that the growth of interest in this area is primarily focused on the larger organization. Not only do large firms feature in the majority of published case studies but also their employees are regular contributors to conference proceedings.This article addresses the comparatively under-researched issue of knowledge and its management in small businesses. Looking beyond formal Knowledge Management (KM) initiatives and structures, emphasis is placed upon the importance of informal knowledge processes.Two related propositions are made: first, knowledge is managed by organizations without use of the language and concepts of KM and accompanying formal KM structures, and that this behaviour might uncontroversially be called `informal' knowledge management, and secondly, small firms are more likely to adopt such informal processes to manage knowledge.These propositions are explored within the context of small firms and the research revealed that small firms do indeed manage knowledge informally as part of their normal activities, without the use of the terminology and concepts of KM. However, contrary to expectations, on occasion some also engage in formal KM.
UK Export Performance Research
Authors: Wheeler Colin , Ibeh Kevin , Dimitratos Pavlos
Published: March 2008

Previous research on export performance has been criticized for being a mosaic of autonomous endeavours and for a lack of theoretical development. Building upon extant models of export performance, and a review and analysis of research on export performance in the UK for the period 1990—2005, an integrated model of export performance is developed and theoretical explanations of export performance are put forward. It is suggested that a multi-theory approach to explaining export performance is viable. Management and policy implications for the UK emerging from the review and synthesis of the literature and the integrated model are discussed.
Poetesses in Classical Sanskrit Literature
Authors: Shah Shalini
Published: March 2008

This article seeks to render audible the voices of poetesses in classical Sanskrit literature between the 7th and 13th centuries C.E., and to juxtapose these voices with the Pālīgāthās of the Therīs, the verses of the Prakrit poetesses as well as the poetry of the Tamil bhaktins. We have argued that while the Sanskrit poetesses were not profes-sional writers, their verses occupy a niche of their own in the corpus of Sanskrit kāvya. The poetry of the Sanskrit poetesses belongs to the prema tradition, which stands in contrast to the hegemonic masculine śrngārī tradition of the rest of the Sanskrit kāvya. We have also argued that in spite of the largely feminine concern of bonding with male partners, there is a subversive quality in these voices that makes many of these Sanskrit verses worthy of being treated as female voices with stirrings of feminist consciousness. A close reading of the verses enlightens us about an entire gendered social world inhabited by these Sanskrit poetesses.
Constructing Women's Image in TV Commercials
Authors: Nina–Pazarzi E. , Tsangaris M.
Published: March 2008

This article is a social semiotic analysis of eight particular TV commercials broadcast in Greek television, and undertakes a historical investigation of advertising representations of basic stereotypic roles of women. Our main hypothesis is that the construction of specific representations reflected the existing power relations characterising patriarchal societies, which in turn influenced the attitudes of advertising networks. Actually, the analysis of women's roles as ‘housewife’ and as ‘sexual object’ did not reveal essential differences through time, while the representations of the ‘working woman’ presented partly conflicting behaviours. Gradually, contradictions in women's representations intensified as the more recent commercials rendered her in more and more roles.
The Role of Structure and Agency in Hunger Reduction in India
Authors: Sridhar Devi
Published: March 2008

This article investigates the role of structure and agency in hunger reduction in India using the case study of the Tamil Nadu Integrated Nutrition Project (TINP). The TINP was a World Bank-funded, state-run project that was initiated in 1980 to improve the nutritional and health status of preschool children, and pregnant and nursing women. Its primary purpose was behavioural change of mothers using the educational tools of growth monitoring, nutrition counselling and supplementary feeding. This paper argues that the predominant cause of undernutrition is not ignorance, but structural factors such as poverty and gender inequality that constrain women's agency. In addition, it examines the representation of the feminised ‘mind’ which is the point of interface between the state and the body.
Reflections on Mobilisation of Rural Peasant Women
Authors: Ray Lokenath
Published: March 2008

A group of rural, poor, uneducated women are my heroes. I have encountered them while working in Medinipur, West Bengal, for a long 10 years and honestly speaking I am filled with humility by the courage and selflessness that these heroes have shown.
Editorial: 'Who are you going to believe — me or your own eyes?' New decade; new directions
Authors: Hartley John
Published: March 2008

This issue of the International Journal of Cultural Studies marks the beginning of its second decade of publication. Since the first issue was published in 1998, we have published about two million freshly minted words — nearly 250 articles on culture, media and everyday life in every continent including Antarctica. John Frow has described the journal as follows: `The International Journal of Cultural Studies is one of the most interesting and innovative showcases of recent work in cultural studies. From Balinese punk to Brazilian television, it's eclectic, adventurous and genuinely international in its range; and it publishes work of a consistently high quality.'
Investigation on TIG cladding of copper alloy on steel plate
Authors: Lv S. X. , Xu Z. W. , Wang H. T. , Yang S. Q.
Published: March 2008

Tungsten inert gas cladding of steel substrate with copper alloy under different processing conditions was investigated with the particular emphasis on the influence of cladding current on the concentration and morphology of Fe solute in the cladding layer and the hardness of the Cu/Fe interface. The application of hot wire was helpful to some extent in improving the spreadability of the filler metal but tended to cause intensive transfer of Fe into the copper layer when the current was higher than 240 A. The increase in Fe concentration in the copper layer followed an exponential relation with the growth of welding current. The morphology of Fe in the copper layer depended on its concentration. The hardness of copper layer increased with the welding current and intensively depended on its Fe content. At a welding rate of 3000 mm min–1, the optimum cladding currents were 210–270 A for the use of cold wire and 210–240 A for the use of hot wire.
Comparison of corrosion modes of oxidation and sulphidation of weld metal with rare earth oxides
Authors: Li Z. Y. , Wang B. , Zhang H. Q.
Published: March 2008

Through addition of rare earth oxides into the coating of electrodes, the high temperature oxidation and sulphidation resistance of weld metal were studied. The weight loss test results showed that the addition of rare earth oxides could improve the high temperature resistance of weld metal, especially in sulphidation environment. The reasons for the difference of corrosion rate between oxidation and suphidation were studied with the application of SEM. It was believed that different corrosion modes were the main reasons for that: oxidation rate was mainly decided by the Cr content of the weld metal and sulphidation rate was mainly decided by the inner corrosion occurring in the grain boundary. The marked effect of rare earth oxides in sulphur environment was related to the corrosion mechanism.
Prediction of the outcome of preoperative chemotherapy in breast cancer using DNA probes that provide information on both complete and incomplete responses
Authors: Natowicz René , Incitti Roberto , Horta Euler Guimarães , Charles Benoît , Guinot Philippe , Yan Kai , Coutant Charles , Andre Fabrice , Pusztai Lajos , Rouzier Roman
Published: March 2008

Background

DNA microarray technology has emerged as a major tool for exploring cancer biology and solving clinical issues. Predicting a patient's response to chemotherapy is one such issue; successful prediction would make it possible to give patients the most appropriate chemotherapy regimen. Patient response can be classified as either a pathologic complete response (PCR) or residual disease (NoPCR), and these strongly correlate with patient outcome. Microarrays can be used as multigenic predictors of patient response, but probe selection remains problematic. In this study, each probe set was considered as an elementary predictor of the response and was ranked on its ability to predict a high number of PCR and NoPCR cases in a ratio similar to that seen in the learning set. We defined a valuation function that assigned high values to probe sets according to how different the expression of the genes was and to how closely the relative proportions of PCR and NoPCR predictions to the proportions observed in the learning set was. Multigenic predictors were designed by selecting probe sets highly ranked in their predictions and tested using several validation sets.

Results

Our method defined three types of probe sets: 71% were mono-informative probe sets (59% predicted only NoPCR, and 12% predicted only PCR), 25% were bi-informative, and 4% were non-informative. Using a valuation function to rank the probe sets allowed us to select those that correctly predicted the response of a high number of patient cases in the training set and that predicted a PCR/NoPCR ratio for validation sets that was similar to that of the whole learning set. Based on DLDA and the nearest centroid method, bi-informative probes proved more successful predictors than probes selected using a t test.

Conclusion

Prediction of the response to breast cancer preoperative chemotherapy was significantly improved by selecting DNA probe sets that were successful in predicting outcomes for the entire learning set, both in terms of accurately predicting a high number of cases and in correctly predicting the ratio of PCR to NoPCR cases.
Using RNase sequence specificity to refine the identification of RNA-protein binding regions
Authors: Wang Xin , Wang Guohua , Shen Changyu , Li Lang , Wang Xinguo , Mooney Sean D , Edenberg Howard J , Sanford Jeremy R , Liu Yunlong
Published: March 2008

Massively parallel pyrosequencing is a high-throughput technology that can sequence hundreds of thousands of DNA/RNA fragments in a single experiment. Combining it with immunoprecipitation-based biochemical assays, such as cross-linking immunoprecipitation (CLIP), provides a genome-wide method to detect the sites at which proteins bind DNA or RNA. In a CLIP-pyrosequencing experiment, the resolutions of the detected protein binding regions are partially determined by the length of the detected RNA fragments (CLIP amplicons) after trimming by RNase digestion. The lengths of these fragments usually range from 50-70 nucleotides. Many genomic regions are marked by multiple RNA fragments. In this paper, we report an empirical approach to refine the localization of protein binding regions by using the distribution pattern of the detected RNA fragments and the sequence specificity of RNase digestion. We present two regions to which multiple amplicons map as examples to demonstrate this approach.
Selection of thermodynamic models for combinatorial control of multiple transcription factors in early differentiation of embryonic stem cells
Authors: Chen Chieh-Chun , Zhu Xin-Guang , Zhong Sheng
Published: March 2008

Background

Transcription factors (TFs) have multiple combinatorial forms to regulate the transcription of a target gene. For example, one TF can help another TF to stabilize onto regulatory DNA sequence and the other TF may attract RNA polymerase (RNAP) to start transcription; alternatively, two TFs may both interact with both the DNA sequence and the RNAP. The different forms of TF-TF interaction have different effects on the probability of RNAP's binding onto the promoter sequence and therefore confer different transcriptional efficiencies.

Results

We have developed an analytical method to identify the thermodynamic model that best describes the form of TF-TF interaction among a set of TF interactions for every target gene. In this method, time-course microarray data are used to estimate the steady state concentration of the transcript of a target gene, as well as the relative changes of the active concentration for each TF. These estimated concentrations and changes of concentrations are fed into an inference scheme to identify the most compatible thermodynamic model. Such a model represents a particular way of combinatorial control by multiple TFs on a target gene.

Conclusions

Applying this approach to a time-course microarray dataset of embryonic stem cells, we have inferred five interaction patterns among three regulators, Oct4, Sox2 and Nanog, on ten target genes.
Evaluation of MHC class I peptide binding prediction servers: Applications for vaccine research
Authors: Lin Hong Huang , Ray Surajit , Tongchusak Songsak , Reinherz Ellis L , Brusic Vladimir
Published: March 2008

Background

Protein antigens and their specific epitopes are formulation targets for epitope-based vaccines. A number of prediction servers are available for identification of peptides that bind major histocompatibility complex class I (MHC-I) molecules. The lack of standardized methodology and large number of human MHC-I molecules make the selection of appropriate prediction servers difficult. This study reports a comparative evaluation of thirty prediction servers for seven human MHC-I molecules.

Results

Of 147 individual predictors 39 have shown excellent, 47 good, 33 marginal, and 28 poor ability to classify binders from non-binders. The classifiers for HLA-A*0201, A*0301, A*1101, B*0702, B*0801, and B*1501 have excellent, and for A*2402 moderate classification accuracy. Sixteen prediction servers predict peptide binding affinity to MHC-I molecules with high accuracy; correlation coefficients ranging from r = 0.55 (B*0801) to r = 0.87 (A*0201).

Conclusion

Non-linear predictors outperform matrix-based predictors. Most predictors can be improved by non-linear transformations of their raw prediction scores. The best predictors of peptide binding are also best in prediction of T-cell epitopes. We propose a new standard for MHC-I binding prediction – a common scale for normalization of prediction scores, applicable to both experimental and predicted data. The results of this study provide assistance to researchers in selection of most adequate prediction tools and selection criteria that suit the needs of their projects.
Characterisation of Shiga toxin-producing Escherichia coliO157 strains isolated from humans in Argentina, Australia and New Zealand
Authors: Leotta Gerardo A , Miliwebsky Elizabeth S , Chinen Isabel , Espinosa Estela M , Azzopardi Kristy , Tennant Sharon M , Robins-Browne Roy M , Rivas Marta
Published: March 2008

Background

Shiga toxin-producing Escherichia coli (STEC) is an important cause of bloody diarrhoea (BD), non-bloody diarrhoea (NBD) and the haemolytic uraemic syndrome (HUS). In Argentina and New Zealand, the most prevalent STEC serotype is O157:H7, which is responsible for the majority of HUS cases. In Australia, on the other hand, STEC O157:H7 is associated with a minority of HUS cases. The main aims of this study were to compare the phenotypic and genotypic characteristics of STEC O157 strains isolated between 1993 and 1996 from humans in Argentina, Australia and New Zealand, and to establish their clonal relatedness.

Results

Seventy-three O157 STEC strains, isolated from HUS (n = 36), BD (n = 20), NBD (n = 10), or unspecified conditions (n = 7) in Argentina, Australia and New Zealand, were analysed. The strains were confirmed to be E. coli O157 by biochemical tests and serotyping. A multiplex polymerase chain reaction (PCR) was used to amplify the stx
1, stx
2 and rfb
O157 genes and a genotyping method based on PCR-RFLP was used to determine stx
1 and stx
2 variants. This analysis revealed that the most frequent stx genotypes were stx
2/stx
2c (vh-a) (91%) in Argentina, stx
2 (89%) in New Zealand, and stx
1/stx
2 (30%) in Australia. No stx
1-postive strains were identified in Argentina or New Zealand. All strains harboured the eae gene and 72 strains produced enterohaemolysin (EHEC-Hly). The clonal relatedness of strains was investigated by phage typing and pulsed-field gel electrophoresis (PFGE). The most frequent phage types (PT) identified in Argentinian, Australian, and New Zealand strains were PT49 (n = 12), PT14 (n = 9), and PT2 (n = 15), respectively. Forty-six different patterns were obtained by XbaI-PFGE; 37 strains were grouped in 10 clusters and 36 strains showed unique patterns. Most clusters could be further subdivided by BlnI-PFGE.

Conclusion

STEC O157 strains isolated in Argentina, Australia, and New Zealand differed from each other in terms of stx-genotype and phage type. Additionally, no common PFGE patterns were found in strains isolated in the three countries. International collaborative studies of the type reported here are needed to detect and monitor potentially hypervirulent STEC clones.
Aedes aegyptiuses RNA interference in defense against Sindbis virus infection
Authors: Campbell Corey L , Keene Kimberly M , Brackney Douglas E , Olson Ken E , Blair Carol D , Wilusz Jeffrey , Foy Brian D
Published: March 2008

Background

RNA interference (RNAi) is an important anti-viral defense mechanism. The Aedes aegypti genome encodes RNAi component orthologs, however, most populations of this mosquito are readily infected by, and subsequently transmit flaviviruses and alphaviruses. The goal of this study was to use Ae. aegypti as a model system to determine how the mosquito's anti-viral RNAi pathway interacts with recombinant Sindbis virus (SINV; family Togaviridae, genus Alphavirus).

Results

SINV (TR339-eGFP) (+) strand RNA, infectious virus titers and infection rates transiently increased in mosquitoes following dsRNA injection to cognate Ago2, Dcr2, or TSN mRNAs. Detection of SINV RNA-derived small RNAs at 2 and 7 days post-infection in non-silenced mosquitoes provided important confirmation of RNAi pathway activity. Two different recombinant SINV viruses (MRE16-eGFP and TR339-eGFP) with significant differences in infection kinetics were used to delineate vector/virus interactions in the midgut. We show virus-dependent effects on RNAi component transcript and protein levels during infection. Monitoring midgut Ago2, Dcr2, and TSN transcript levels during infection revealed that only TSN transcripts were significantly increased in midguts over blood-fed controls. Ago2 protein levels were depleted immediately following a non-infectious bloodmeal and varied during SINV infection in a virus-dependent manner.

Conclusion

We show that silencing RNAi components in Ae. aegypti results in transient increases in SINV replication. Furthermore, Ae. aegypti RNAi is active during SINV infection as indicated by production of virus-specific siRNAs. Lastly, the RNAi response varies in a virus-dependent manner. These data define important features of RNAi anti-viral defense in Ae. aegypti.
The use of interim data and Data Monitoring Committee recommendations in randomized controlled trial reports: frequency, implications and potential sources of bias
Authors: Tharmanathan Puvan , Calvert Melanie , Hampton John , Freemantle Nick
Published: March 2008

Background

Interim analysis of accumulating trial data is important to protect participant safety during randomized controlled trials (RCTs). Data Monitoring Committees (DMCs) often undertake such analyses, but their widening role may lead to extended use of interim analysis or recommendations that could potentially bias trial results.

Methods

Systematic search of eight major publications: Annals of Internal Medicine, BMJ, Circulation, CID, JAMA, JCO, Lancet and NEJM, including all randomised controlled trials (RCTs) between June 2000 and May 2005 to identify RCTs that reported use of interim analysis, with or without DMC involvement. Recommendations made by the DMC or based on interim analysis were identified and potential sources of bias assessed. Independent double data extraction was performed on all included trials.

Results

We identified 1772 RCTs, of which 470 (27%; 470/1772) reported the use of a DMC and a further 116 (7%; 116/1772) trials reported some form of interim analysis without explicit mention of a DMC. There were 28 trials (24 with a formal DMC), randomizing a total of 79396 participants, identified as recommending changes to the trial that may have lead to biased results. In most of these, some form of sample size re-estimation was recommended with four trials also reporting changes to trial endpoints. The review relied on information reported in the primary publications and methods papers relating to the trials, higher rates of use may have occurred but not been reported.

Conclusion

The reported use of interim analysis and DMCs in clinical trials has been increasing in recent years. It is reassuring that in most cases recommendations were made in the interest of participant safety. However, in practice, recommendations that may lead to potentially biased trial results are being made.
Expression of TNF-superfamily members BAFF and APRIL in breast cancer: Immunohistochemical study in 52 invasive ductal breast carcinomas
Authors: Pelekanou Vassiliki , Kampa Marilena , Kafousi Maria , Darivianaki Katerina , Sanidas Elias , Tsiftsis Dimitrios D , Stathopoulos Efstathios N , Tsapis Andreas , Castanas Elias
Published: March 2008

Background

Recent studies suggest an association between chronic inflammation, modulating the tissue microenvironment, and tumor biology. Tumor environment consists of tumor, stromal and endothelial cells and infiltrating macrophages, T lymphocytes, and dendritic cells, producing an array of cytokines, chemokines and growth factors, accounting for a complex cell interaction and regulation of differentiation, activation, function and survival of tumor and surrounding cells, responsible for tumor progression and spreading or induction of antitumor immune responses and rejection. Tumor Necrosis Factor (TNF) family members (19 ligands and 29 receptors) represent a pleiotropic family of agents, related to a plethora of cellular events from proliferation and differentiation to apoptosis and tumor reduction. Among these members, BAFF and APRIL (CD257 and CD256 respectively) gained an increased interest, in view of their role in cell protection, differentiation and growth, in a number of lymphocyte, epithelial and mesenchymal structures.

Methods

We have assayed by immunohistochemistry 52 human breast cancer biopsies for the expression of BAFF and APRIL and correlated our findings with clinicopathological data and the evolution of the disease.

Results

BAFF was ubiquitely expressed in breast carcinoma cells, DCIS, normal-appearing glands and ducts and peritumoral adipocytes. In contrast, APRIL immunoreactive expression was higher in non-malignant as compared to malignant breast structures. APRIL but not BAFF immunoreactivity was higher in N+ tumors, and was inversely related with the grade of the tumors. Neither parameter was related to DFS or the OS of patients.

Conclusion

Our data show, for the first time, an autocrine secretion of BAFF and APRIL from breast cancer cells, offering new perspectives for their role in neoplastic and normal breast cell biology and offering new perspectives for possible selective intervention in breast cancer.
Hypermethylated MAL gene – a silent marker of early colon tumorigenesis
Authors: Lind Guro E , Ahlquist Terje , Kolberg Matthias , Berg Marianne , Eknæs Mette , Alonso Miguel A , Kallioniemi Anne , Meling Gunn I , Skotheim Rolf I , Rognum Torleiv O , Thiis-Evensen Espen , Lothe Ragnhild A
Published: March 2008

Background

Tumor-derived aberrantly methylated DNA might serve as diagnostic biomarkers for cancer, but so far, few such markers have been identified. The aim of the present study was to investigate the potential of the MAL (T-cell differentiation protein) gene as an early epigenetic diagnostic marker for colorectal tumors.

Methods

Using methylation-specific polymerase chain reaction (MSP) the promoter methylation status of MAL was analyzed in 218 samples, including normal mucosa (n = 44), colorectal adenomas (n = 63), carcinomas (n = 65), and various cancer cell lines (n = 46). Direct bisulphite sequencing was performed to confirm the MSP results. MAL gene expression was investigated with real time quantitative analyses before and after epigenetic drug treatment. Immunohistochemical analysis of MAL was done using normal colon mucosa samples (n = 5) and a tissue microarray with 292 colorectal tumors.

Results

Bisulphite sequencing revealed that the methylation was unequally distributed within the MAL promoter and by MSP analysis a region close to the transcription start point was shown to be hypermethylated in the majority of colorectal carcinomas (49/61, 80%) as well as in adenomas (45/63, 71%). In contrast, only a minority of the normal mucosa samples displayed hypermethylation (1/23, 4%). The hypermethylation of MAL was significantly associated with reduced or lost gene expression in in vitro models. Furthermore, removal of the methylation re-induced gene expression in colon cancer cell lines. Finally, MAL protein was expressed in epithelial cells of normal colon mucosa, but not in the malignant cells of the same type.

Conclusion

Promoter hypermethylation of MAL was present in the vast majority of benign and malignant colorectal tumors, and only rarely in normal mucosa, which makes it suitable as a diagnostic marker for early colorectal tumorigenesis.
Carbonic anhydrase IX and response to postmastectomy radiotherapy in high-risk breast cancer: a subgroup analysis of the DBCG82 b and c trials
Authors: Kyndi Marianne , Sørensen Flemming B , Knudsen Helle , Alsner Jan , Overgaard Marie , Nielsen Hanne M , Overgaard Jens
Published: March 2008

Introduction

A significant survival improvement after postmastectomy radiotherapy was identified in the Danish Breast Cancer Cooperative Group (DBCG82) b and c studies and in the British Columbia Randomized Radiation Trial. Recently, potential predictive value regarding response to postmastectomy radiotherapy was reported for carbonic anhydrase (CA) IX in a study (reported in abstract form) that included 160 patients. The purpose of the present study was to examine the importance of CA IX to response to postmastectomy radiotherapy in the larger scaled DBCG82 b and c studies.

Methods

The DBCG82 b and c studies included 3,083 high-risk Danish breast cancer patients. The women were randomly assigned to postmastectomy radiotherapy plus systemic therapy (cyclophosfamide, methotrexate and fluorouracil in premenopausal women; and tamoxifen in postmenopausal women) or to systemic therapy alone. Cores from invasive tumour-containing paraffin blocks from 1,000 patients (more than seven nodes surgically removed) were transferred to tissue microarrays. Tissue microarray sections were stained immunohistochemically for CA IX (M75). The median follow up for patients remaining alive was 17 years. Clinical end-points were loco-regional recurrence, distant metastases, disease-specific survival and overall survival. Statistical analyses included κ statistics, χ2 or exact tests, Kaplan-Meier probability plots, Log-rank test and Cox regression analyses.

Results

CA IX was assessable in 945 cores. The percentage of tumours positive for CA IX was 16% (≥ 10% invasive tumour staining). CA IX was not an independent prognostic marker for survival, distant metastases, or locoregional recurrence in the subgroup of 945 patients or within either of the two randomization arms. In subgroup analyses, however, CA IX was an independent prognostic marker for overall survival among postmenopausal women (P = 0.001), women with one to three positive nodes (P = 0.02) and hormone receptor positive women (P = 0.001). Fifteen-year probabilities of overall survival were improved by 9% and 7% after postmastectomy radiotherapy for the subgroups of CA IX negative and CA IX positive patients, respectively.

Conclusion

Within this series of 945 high-risk premenopausal and postmenopausal women, positivity for CA IX was not overall an independent prognostic marker for survival; only in subgroup analyses was it found to have prognostic value. The improvement in 15-year survival after postmastectomy radiotherapy was of similar magnitude in the two subgroups of CA IX positive and CA IX negative patients.
Localized Infant Neuroblastomas Often Show Spontaneous Regression: Results of the Prospective Trials NB95-S and NB97
Authors: Hero Barbara , Simon Thorsten , Spitz Ruediger , Ernestus Karen , Gnekow Astrid K. , Scheel-Walter Hans-Guenther , Schwabe Dirk , Schilling Freimut H. , Benz-Bohm Gabriele , Berthold Frank
Published: March 2008

Purpose

The excellent prognosis of localized neuroblastoma in infants, the overdiagnosis observed in neuroblastoma screening studies, and several case reports of regression of localized neuroblastoma prompted us to initiate a prospective cooperative trial on observation of localized neuroblastoma without cytotoxic treatment.

Patients and Methods

For infants with localized neuroblastoma without MYCN amplification, chemotherapy was scheduled only in cases with threatening symptoms; otherwise, the tumor was either resected or observed by ultrasound and magnetic resonance imaging (MRI).

Results

Of 340 eligible participants, 190 underwent resection, 57 were treated with chemotherapy, and 93 were observed with gross residual tumor. Of those 93 patients with unresected tumors, spontaneous regression was seen in 44, local progression in 28, progression to stage 4S in seven, and progression to stage 4 in four. Time to regression was quite variable, with first signs of regression noted 1 to 18 months after diagnosis and in 15 of 44 patients even after the first year of life. So far, complete regression was observed in 17 of 44 patients 4 to 20 months after diagnosis. Known clinical risk factors were not able to differentiate between patients with regression and regional or metastatic progression. Overall survival (OS; 3-year OS, 0.99 ± 0.01) and metastases-free survival (rate at 3 years, 0.94 ± 0.03) for patients with unresected tumors was excellent and was not different from patients treated with surgery or chemotherapy.

Conclusion

Spontaneous regression is regularly seen in infants with localized neuroblastoma and is not limited to the first year of life. A wait-and-see strategy is justified in those patients.
The mutationROR2W749X, linked to human BDB, is a recessive mutation in the mouse, causing brachydactyly, mediating patterning of joints and modeling recessive Robinow syndrome
Authors: Raz Regina , Stricker Sigmar , Gazzerro Elizabetta , Clor Julie L. , Witte Florian , Nistala Harakiran , Zabski Stefanie , Pereira Renata C. , Stadmeyer Lisa , Wang Xiangmin , Gowen Lori , Sleeman Mark W. , Yancopoulos George D. , Canalis Ernesto , Mundlos Stefan , Valenzuela David M. , Economides Aris N.
Published: March 2008

Mutations in ROR2 result in a spectrum of genetic disorders in humans that are classified, depending on the nature of the mutation and the clinical phenotype, as either autosomal dominant brachydactyly type B (BDB,MIM 113000) or recessive Robinow syndrome (RRS, MIM 268310). In an attempt to model BDB in mice, the mutation W749X was engineered into the mouse Ror2 gene. In contrast to the human situation, mice heterozygous for Ror2W749FLAG are normal and do not develop brachydactyly,whereas homozygous mice exhibit features resembling RRS. Furthermore, both Ror2W749FLAG/W749FLAG and a previously engineered mutant, Ror2TMlacZ/TMlacZ, lack the P2/P3 joint. Absence of Gdf5 expression at the corresponding interzone suggests that the defect is in specification of the joint. As this phenotype is absent in mice lacking the entire Ror2 gene, it appears that specification of the P2/P3 joint is affected by ROR2 activity. Finally, Ror2W749FLAG/W749FLAG mice survive to adulthood and exhibit phenotypes (altered body composition, reduced male fertility) not observed in Ror2 knockout mice, presumably due to the perinatal lethality of the latter. Therefore, Ror2W749FLAG/W749FLAGmice represent a postnatal model for RRS, provide insight into the mechanism of joint specification, and uncover novel roles of Ror2 in the mouse.
Dynamic behaviour of high‐strength sheet steel in dynamic tension: Experimental and numerical analyses
Authors: Rusinek A , Cheriguene R , Bäumer A , Larour P
Published: March 2008

This paper presents the behaviour of high‐strength steel TRIP 700, frequently applied in automotive industries. This material is used to design some car components owing to high stress levels induced by phase transformation. Generally, a pre‐plastic deformation is induced in the sheet steel at a low strain rate to transform austenite into martensite. The next step is to design for example a crash box, as described previously by Durrenberger et al. [1], in order to increase the level of energy absorption. The problem with testing this material is the specimen attachment during the tension test, notably at intermediate and high strain rates. A special problem appears when this material is used for crash applications, namely the plastic behaviour at intermediate strain rates 50 s−1εεε3×102 s−1 and for the maximum stress level observed at εmax≈103 s−1 must be defined correctly. In order to evaluate the behaviour of materials for this range of strain rates, servohydraulic machines are used. However, even if the actuator allows for velocities V0≥10 m/s, usually some problems appear during force measurement because the natural frequency of the load cell is too low. Even using a piezoelectric load cell, the material behaviour cannot be defined precisely. In order to obtain more precise information by force measurement, resistance strain gauges are generally used. One possibility is to cement these on to the specimen head. However, using this technique it is necessary to have a good knowledge of the parasite effects as discussed in this paper. Therefore, a coupled experiment‐numerical simulation allows some effects due to the specimen design and resistance gauge position to be demonstrated.
A test rig for investigations of gas turbine combustor cooling concepts under realistic operating conditions
Authors: Behrendt T , Hassa Ch
Published: March 2008

In the current paper, a new test rig for the characterization of advanced combustor cooling concepts for gas turbine combustors is presented. The test rig is designed to allow investigations at elevated pressures and temperatures representing realistic operating conditions of future lean low emission combustors. The features and capabilities of the test rig in comparison to existing rigs are described. The properties of the hot gas flow are measured in order to provide the necessary data for a detailed analysis of the measured cooling effectivity of combustor wall test samples. Results of the characterization of the velocity and temperature distribution in the hot gas flow at the leading edge of the test sample at pressures up to p = 10 bar and global flame temperatures up to TF = 2000 K are presented.
Uncertainty-based model-order reduction of flexible systems preserving robust closed-loop performance
Authors: Aouf N , Boulet B
Published: March 2008

In the current paper, initial research results on uncertainty-based closed-loop model-order reduction techniques for flexible systems are detailed. Two uncertainty models to decide what flexible modes to be truncated from the original flexible system model while preserving closed-loop performance are presented. Robust control framework is used with the robust performance criterion to show that the new inverse uncertainty representation of flexible modes gives better closed-loop performance than the more classical additive uncertainty representation adapted, in the current paper, for flexible systems. Simulation based on a three mass flexible model validates the good results of the inverse uncertainty model-order reduction technique.
A disturbance rejection-based control system design for Z-axis vibratory rate gyroscopes
Authors: Zheng Q , Dong L
Published: March 2008

The current paper presents a new control strategy known as active disturbance rejection control (ADRC) for controlling the sense axis of a vibrational microelectromechanical system (MEMS) gyroscope and detecting time-varying rotation rates. In the ADRC framework, the generalized disturbance, which is referred to as the combination of the internal dynamics and external disturbances, is estimated and compensated for in real time. It is assumed that the drive axis outputs an ideal sinusoidal signal. A force-to-rebalance mode of operation is applied to the sense axis of the gyroscope. Under this mode, the output of the sense axis is continuously monitored and driven to zero by ADRC and the rotation rate is estimated by employing the demodulation technique. Simulation results and performance analysis demonstrate the effectiveness and robustness of the ADRC against parameter variations and noises.
Adaptive stabilization of non-linear systems at unknown equilibrium points: An invariant manifold and uniform δ-persistent excitation approach
Authors: Duarte-Mermoud M A , Estrada J L , Travieso-Torres J C
Published: March 2008

The adaptive stabilization of a class of continuous-time non-linear systems (not necessarily chaotic) at the unknown equilibrium points is treated in this paper. The controller is designed based on the invariant manifold theory and on the concept of uniform δ-persistent excitation (U δ-PE). Firstly, the case when there are no constraints on the parameter estimates is presented and then the case when the parameter estimates are confined to a certain region is discussed. In the last case the proposed alternative does not require knowledge of bounds but new estimates have to be introduced. Finally, the behaviour of the proposed scheme is verified through simulations on the Lorenz system for both chaotic and non-chaotic cases.
Novel Photoreaction Using Diphenyl Disulfide Derivatives: Photoinduced Oxidation of Allyl Alcohol
Authors: Tsuboi Takaaki , Takaguchi Yutaka , Tsuboi Sadao
Published: March 2008

Allyl alcohols are oxidized to acrylaldehydes using diphenyl disulfide derivatives upon photoirradiation. The reaction occurs via α-hydrogen abstraction by a sulfanyl radical. Interestingly, the oxidation reaction occurs in moderate yield when a dendrimer disulfide is used as a mediator.
Mesomorphic Effect of Discotic-type Liquid-crystalline Compounds as Neutral Carriers on Potentiometric Ion-sensing Membranes
Authors: Moriuchi-Kawakami Takayo , Nishimura Hiroshi , Shibutani Yasuhiko , Sugino Takushi , Shimizu Yo
Published: March 2008

Mesomorphic porphyrin, 5,10,15,20-tetrakis(4-n-dodecylphenyl)porphyrin (C12TPPH2) and the cobalt complex C12TPPCo were used as neutral carriers of ion-selective electrodes (ISEs) to investigate the mesomorphic effect in potentiometric cation- and anion-sensing membranes. The selectivity coefficiency of a potentiometric cation-sensing membrane incorporating C12TPPH2 was drastically affected by heat-induced phase transitions of ionophoric liquid-crystalline compound. This paper is the first report that proved the heat-induced phase transition of ionophoric liquid-crystalline compound in the potentiometric ion-sensing membrane. It is noteworthy that selectivity sequence of the potentiometric cation-sensing membrane is remarkable changed by the mesomorphic effect. Furthermore, mesomorphic effect on a potentiometric anion-sensing membrane incorporating C12TPPCo was also demonstrated.
Management of Parkinson's disease in older women
Authors: Price Molly Daymont , Shulman Lisa M
Published: March 2008

Elderly women with Parkinson's disease (PD) represent a specific patient population that may benefit from individualized treatment strategies. PD has been shown to occur approximately twice as often in men than in women, resulting in theories regarding estrogen being protective against the disease and as a potential treatment strategy. Given women's longer life expectancy they are more likely to reach an age where antiparkinsonian medications are associated with side-effects. This paper will review medical and surgical treatments as well as the relationship of gender and age with respect to the management of PD.
Adsorption of Oxalic Acid onto Hematite: Application of Surface Potential Measurements
Authors: Preočanin Tajana , Majić Željka , Kovačević Davor , Kallay Nikola
Published: March 2008

The surface potential at the hematite/aqueous oxalic acid interface was measured by means of a hematite Single Crystal Electrode. This allowed the simultaneous interpretation of the surface potential, electrokinetic potential and adsorption data for the adsorption of oxalic acid onto a hematite surface. Based on the Surface Complexation Model, this interpretation suggested that the oxalate ion is bound to a metal ion at the solid surface to form a singly-charged oxalate-surface complex, with the charge being exposed to the potential at the outer Helmholtz layer. A number of equilibrium parameters describing the interfacial equilibrium were obtained. Thus, for the two protonation steps of the surface sites, the thermodynamic equilibrium constants were log K1 = 7.1 ± 0.4 and log K2 = 5.2 ± 0.4, respectively. Two assumptions were tested with regard to the adsorption equilibrium constant, i.e. the charge of the surface complex is exposed to the inner surface potential, ψ0, or to the outer surface potential, ψd. The constancy of the interfacial equilibrium constants led to the conclusion the latter assumption was the more appropriate. The observed value of the adsorption equilibrium constant was log Kads = 3.0 ± 0.8. It was shown that measurement of the surface potential by Single Crystal Electrodes is a helpful tool in elucidating the equilibrium behaviour of the complex at the interface.
Effects of Surface Structure and Temperature on the Surface Mediation, Layer Concentration and Molecular Projection Area: Adsorption of Argon and Nitrogen onto Graphitized Thermal Carbon Black
Authors: Do D.D. , Do H.D. , Nicholson D.
Published: March 2008

This paper is devoted to an investigation of the effects of surface structure (structure-less or structured) on the description of the adsorption isotherm and the isosteric heat of nitrogen and argon adsorption onto graphitized thermal carbon black. It was found that the surface structure had little effect on the adsorption of either argon or nitrogen at 77 K and 87.3 K. The variation of the monolayer coverage concentration was also investigated as well as the concentrations of higher layers as a function of pressure and temperature. Finally, the commonly used values for the molecular projection area of nitrogen and argon for graphitized thermal carbon black (16.2 Å2 and 13.8 Å2) were revisited. For this material, a value of 15.5 Å2 is recommended for nitrogen at 77 K, while for the case of argon at the same temperature the recommended values of 13.8 Å2 and 12.94 Å2 are suggested for the reduced pressure range (0.1–0.2P/P0) and (0.25–0.35P/P0), respectively. A value of 14 Å2 for argon at 87.3 K is suggested for the BET plot over the reduced pressure range of 0.1–0.2P/P0.
Student and Stakeholder Perceptions of the Transition to High School
Authors: Smith Joshua S. , Akos Patrick , Lim Sungtaek , Wiley Shanna
Published: March 2008

A mixed method, longitudinal design was used to assess student and stakeholder perceptions of the transition to high school. Comparisons between parent and student perceptions revealed few differences and both groups were generally optimistic about entering the Freshmen Center. Following the transition, student perceptions exhibited important changes that point to a need for clarifying the academic, social, and organizational similarities and differences between the two grade levels. Interviews with school staff revealed concerns particularly about differences in high school assessment and disciplinary practices. Implications of the data and practical applications for high school transition programming are presented.