bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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

AbstractBackgroundProtein 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.ResultsOf 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).ConclusionNon-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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract
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.
Novel Photoreaction Using Diphenyl Disulfide Derivatives: Photoinduced Oxidation of Allyl Alcohol
Authors: Tsuboi Takaaki , Takaguchi Yutaka , Tsuboi Sadao 
Published: March 2008

Abstract
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

Abstract
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.
Comparison of Skeletal Effects of Ovariectomy Versus Chemically Induced Ovarian Failure in Mice
Authors: Wright Laura E , Christian Patricia J , Rivera Zelieann , Van Alstine William G , L Funk Janet , L Bouxsein Mary , Hoyer Patricia B 
Published: March 2008

Abstract
Bone loss associated with menopause leads to an increase in skeletal fragility and fracture risk. Relevant animal models can be useful for evaluating the impact of ovarian failure on bone loss. A chemically induced model of menopause in which mice gradually undergo ovarian failure yet retain residual ovarian tissue has been developed using the chemical 4-vinylcyclohexene diepoxide (VCD). This study was designed to compare skeletal effects of VCD-induced ovarian failure to those associated with ovariectomy (OVX). Young (28 day) C57Bl/6Hsd female mice were dosed daily with vehicle or VCD (160 mg/kg/d, IP) for 15 days (n = 6–7/group) and monitored by vaginal cytology for ovarian failure. At the mean age of VCD-induced ovarian failure (∼6 wk after onset of dosing), a different group of mice was ovariectomized (OVX, n = 8). Spine BMD (SpBMD) was measured by DXA for 3 mo after ovarian failure and OVX. Mice were killed ∼5 mo after ovarian failure or OVX, and bone architecture was evaluated by μCT ex vivo. In OVX mice, SpBMD was lower than controls 1 mo after OVX, whereas in VCD-treated mice, SpBMD was not lower than controls until 2.9 mo after ovarian failure (p &lt; 0.05). Both VCD-induced ovarian failure and OVX led to pronounced deterioration of trabecular bone architecture, with slightly greater effects in OVX mice. At the femoral diaphysis, cortical bone area and thickness did not differ between VCD mice and controls but were decreased in OVX compared with both groups (p &lt; 0.05). Circulating androstenedione levels were preserved in VCD-treated mice but reduced in OVX mice relative to controls (p &lt; 0.001). These findings support that (1) VCD-induced ovarian failure leads to trabecular bone deterioration, (2) bone loss is attenuated by residual ovarian tissue, particularly in diaphyseal cortical bone, and (3) the VCD mouse model can be a relevant model for natural menopause in the study of associated bone disorders.