bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reduced expression of N-Myc downstream-regulated gene 2 in human thyroid cancer
Authors: Zhao Huadong , Zhang Jian , Lu Jianguo , He Xianli , Chen Changsheng , Li Xiaojun , Gong Li , Bao Guoqiang , Fu Qiang , Chen Suning , Lin Wei , Shi Hai , Ma Jianjun , Liu Xinping , Ma Qingjiu , Yao Libo 
Published: October 2008

Abstract

Background

NDRG2 (N-Myc downstream-regulated gene 2) was initially cloned in our laboratory. Previous results have shown that NDRG2 expressed differentially in normal and cancer tissues. Specifically, NDRG2 mRNA was down-regulated or undetectable in several human cancers, and over-expression of NDRG2 inhibited the proliferation of cancer cells. NDRG2 also exerts important functions in cell differentiation and tumor suppression. However, it remains unclear whether NDRG2 participates in carcinogenesis of the thyroid.

Methods
In this study, we investigated the expression profile of human NDRG2 in thyroid adenomas and carcinomas, by examining tissues from individuals with thyroid adenomas (n = 40) and carcinomas (n = 35), along with corresponding normal tissues. Immunohistochemistry, quantitative RT-PCR and western blot methods were utilized to determine both the protein and mRNA expression status of Ndrg2 and c-Myc.

Results
The immunostaining analysis revealed a decrease of Ndrg2 expression in thyroid carcinomas. When comparing adenomas or carcinomas with adjacent normal tissue from the same individual, the mRNA expression level of NDRG2 was significantly decreased in thyroid carcinoma tissues, while there was little difference in adenoma tissues. This differential expression was confirmed at the protein level by western blotting. However, there were no significant correlations of NDRG2 expression with gender, age, different histotypes of thyroid cancers or distant metastases.

Conclusion
Our data indicates that NDRG2 may participate in thyroid carcinogenesis. This finding provides novel insight into the important role of NDRG2 in the development of thyroid carcinomas. Future studies are needed to address whether the down-regulation of NDRG2 is a cause or a consequence of the progression from a normal thyroid to a carcinoma.
Leptin/HER2 crosstalk in breast cancer: in vitro study and preliminary in vivoanalysis
Authors: Fiorio Elena , Mercanti Anna , Terrasi Marianna , Micciolo Rocco , Remo Andrea , Auriemma Alessandra , Molino Annamaria , Parolin Veronica , Di Stefano Bruno , Bonetti Franco , Giordano Antonio , Cetto Gian Luigi , Surmacz Eva 
Published: October 2008

Abstract

Background
Obesity in postmenopausal women is associated with increased breast cancer risk, development of more aggressive tumors and resistance to certain anti-breast cancer treatments. Some of these effects might be mediated by obesity hormone leptin, acting independently or modulating other signaling pathways. Here we focused on the link between leptin and HER2. We tested if HER2 and the leptin receptor (ObR) can be coexpressed in breast cancer cell models, whether these two receptors can physically interact, and whether leptin can transactivate HER2. Next, we studied if leptin/ObR can coexist with HER2 in breast cancer tissues, and if presence of these two systems correlates with specific clinicopathological features.

Methods
Expression of ObR, HER2, phospo-HER2 was assessed by immonoblotting. Physical interactions between ObR and HER2 were probed by immunoprecipitation and fluorescent immunostaining. Expression of leptin and ObR in breast cancer tissues was detected by immunohistochemistry (IHC). Associations among markers studied by IHC were evaluated using Fisher's exact test for count data.

Results
HER2 and ObR were coexpressed in all studied breast cancer cell lines. In MCF-7 cells, HER2 physically interacted with ObR and leptin treatment increased HER2 phosphorylation on Tyr 1248. In 59 breast cancers, the presence of leptin was correlated with ObR (the overall association was about 93%). This result was confirmed both in HER2-positive and in HER2-negative subgroups. The expression of leptin or ObR was numerically more frequent in larger (> 10 mm) tumors.

Conclusion
Coexpression of HER2 and the leptin/ObR system might contribute to enhanced HER2 activity and reduced sensitivity to anti-HER2 treatments.
SELDI-TOF-MS determination of hepcidin in clinical samples using stable isotope labelled hepcidin as an internal standard
Authors: Ward Douglas G , Roberts Keith , Stonelake Paul , Goon Patrick , Zampronio Cleidiane G , Martin Ashley , Johnson Philip J , Iqbal Tariq , Tselepis Chris 
Published: October 2008

Abstract

Background
Hepcidin is a 25-residue peptide hormone crucial to iron homeostasis. It is essential to measure the concentration of hepcidin in cells, tissues and body fluids to understand its mechanisms and roles in physiology and pathophysiology. With a mass of 2791 Da hepcidin is readily detectable by mass spectrometry and LC-ESI, MALDI and SELDI have been used to estimate systemic hepcidin concentrations by analysing serum or urine. However, peak heights in mass spectra may not always reflect concentrations in samples due to competition during binding steps and variations in ionisation efficiency. Thus the purpose of this study was to develop a robust assay for measuring hepcidin using a stable isotope labelled hepcidin spiking approach in conjunction with SELDI-TOF-MS.

Results
We synthesised and re-folded hepcidin labelled with 13C/15N phenylalanine at position 9 to generate an internal standard for mass spectrometry experiments. This labelled hepcidin is 10 Daltons heavier than the endogenous peptides and does not overlap with the isotopic envelope of the endogenous hepcidin or other common peaks in human serum or urine mass spectra and can be distinguished in low resolution mass spectrometers. We report the validation of adding labelled hepcidin into serum followed by SELDI analysis to generate an improved assay for hepcidin.

Conclusion
We demonstrate that without utilising a spiking approach the hepcidin peak height in SELDI spectra gives a good indication of hepcidin concentration. However, a stable isotope labelled hepcidin spiking approach provides a more robust assay, measures the absolute concentration of hepcidin and should facilitate inter-laboratory hepcidin comparisons.
Rescaling quality of life values from discrete choice experiments for use as QALYs: a cautionary tale
Authors: Flynn Terry N , Louviere Jordan J , Marley Anthony AJ , Coast Joanna , Peters Tim J 
Published: October 2008

AbstractBackgroundResearchers are increasingly investigating the potential for ordinal tasks such as ranking and discrete choice experiments to estimate QALY health state values. However, the assumptions of random utility theory, which underpin the statistical models used to provide these estimates, have received insufficient attention. In particular, the assumptions made about the decisions between living states and the death state are not satisfied, at least for some people. Estimated values are likely to be incorrectly anchored with respect to death (zero) in such circumstances.MethodsData from the Investigating Choice Experiments for the preferences of older people CAPability instrument (ICECAP) valuation exercise were analysed. The values (previously anchored to the worst possible state) were rescaled using an ordinal model proposed previously to estimate QALY-like values. Bootstrapping was conducted to vary artificially the proportion of people who conformed to the conventional random utility model underpinning the analyses.ResultsOnly 26% of respondents conformed unequivocally to the assumptions of conventional random utility theory. At least 14% of respondents unequivocally violated the assumptions. Varying the relative proportions of conforming respondents in sensitivity analyses led to large changes in the estimated QALY values, particularly for lower-valued states. As a result these values could be either positive (considered to be better than death) or negative (considered to be worse than death).ConclusionUse of a statistical model such as conditional (multinomial) regression to anchor quality of life values from ordinal data to death is inappropriate in the presence of respondents who do not conform to the assumptions of conventional random utility theory. This is clearest when estimating values for that group of respondents observed in valuation samples who refuse to consider any living state to be worse than death: in such circumstances the model cannot be estimated. Only a valuation task requiring respondents to make choices in which both length and quality of life vary can produce estimates that properly reflect the preferences of all respondents.
Outcome in patients with enthesitis related arthritis (ERA): juvenile arthritis damage index (JADI) and functional status
Authors: Sarma Pradip Kumar , Misra Ramnath , Aggarwal Amita 
Published: October 2008

Abstract

Background
Data on outcome of ERA is scarce and there is lack of well-accepted tools. JADI is a newly described outcome measure in JIA that has not been evaluated in ERA. We studied outcome in ERA using JADI and correlated it with traditional outcome measures.

Methods
We studied 49 consecutive patients of ERA with age ≥ 5 years and duration ≥ 1 year. Along with JADI, we recorded enthesitis, lumbar spinal anterior flexion by modified Schober's method, presence of inflammatory backache, loss of school years, HAQ-S, growth and pubertal delay. Parent's/patient's and physician's global assessments on 100 mm visual analogue scale.

Results
The median age was 18.0 (10–27) years and the median duration of disease was 6.0 (1–17) years. All the patients were male and half (53.1%) were HLA B 27 positive. Fourteen had decreased anterior lumbar flexion movement and 32 had inflammatory backache. Active enthesitis was present in 63.3%. Functionally, mild, moderate and severe disability was seen in 18.4%, 34.7% & 14.3% respectively. Sixty five percent of patients lost education years. Twenty-eight patients had damaged joints with median of 2.0 joints (0–9). Seventeen patients (34.7%) had damaged joints in JADI-A score with a median of 1.0 (0–12). Growth failure was the commonest extra articular damage (8.2%) in JADI-E. JADI correlated with HAQ-S, parent's or patient's & physician's global assessment (p < 0.01). Limitation of spinal mobility had high correlation with HAQ-S; correlation with JADI-A was low.

Conclusion
Three fourth of the ERA patients had functional limitations. Half of the patients had damaged joints. Even though JADI correlated well with traditional outcome measures, it underestimates joint damage, and does not assess enthesitis and spinal limitation which affect functional status in ERA. Inclusion of these may make it more useful for ERA.
Morphology and head morphometric characters of sperm in Thai native crossbred stallions
Authors: Phetudomsinsuk Kanittha , Sirinarumitr Kaitkanoke , Laikul Aree , Pinyopummin Anuchai 
Published: October 2008

AbstractBackgroundOne of the semen quality parameters use to determine fertility is the percentage of sperm that express normal morphology. Sperm head morphometry is also correlated with fertility. The objectives of this study were 1) to investigate the sperm morphology and normal sperm head morphometry of Thai native crossbred stallions, and 2) to compare our results with the characteristics of proven fertile sperm from purebred stallions.MethodsSemen samples were collected monthly from nine stallions, of which five were Thai native crossbred (T) and four were purebred of proven fertility (F: F1 was a Standard-bred; F2 was a Warm-blood; F3 and F4 were Thoroughbreds). All the animals were aged between 5 and 12 years. Sperm morphological examination was performed using formaldehyde-fixed samples under phase-contrast microscopy (1000×). Normal sperm head morphometry characteristics were measured by Computer-Assisted Semen Analysis (Hamilton Thorne, USA.) after applying the Harris' haematoxylin staining technique.ResultsThe percentages of morphologically normal and abnormal sperm varied among individual stallions in both the T and F groups. The mean percentage of morphologically normal sperm was not significantly different (P > 0.05) between T and F stallions (mean ± SE, 49.7 ± 1.3 and 48.1 ± 2.8, respectively). A comparison between the T and F sperm heads revealed that all the dimensional parameters were significantly different (P < 0.05). The coefficients of within-animal variation (CVs) ranged from 2.6 (shape factor 1) to 7.5 (elongation) and 2.9 (shape factor 1) to 8.1 (elongation) in T and F, respectively. In the case of the T group, those sperm head parameters that featured a low within-animal CV and a high between-animal CV were perimeter (2.9, 19.1), shape factor 1 (2.6, 25.8) and shape factor 3 (3.8, 32.0). In the case of the F group, only shape factor 1 (2.9, 26.1) featured such characteristics.ConclusionWe found variability in the percentage of morphologically normal and abnormal sperm, as well as in sperm head dimensions among Thai native crossbred stallions, and these results were similar to those of purebred stallions. Our findings demonstrate that the heads of the T sperm specimens were larger and rounder than that of the F sperm. Perimeter, shape factor 1 and shape factor 3 could be used as parameters for the identification of individual T stallions based on a sperm sample.
Analysis of saccharification in Brachypodium distachyon stems under mild conditions of hydrolysis
Authors: Gomez Leonardo D , Bristow Jennifer K , Statham Emily R , McQueen-Mason Simon J 
Published: October 2008

Abstract

Background

Brachypodium distachyon constitutes an excellent model species for grasses. It is a small, easily propagated, temperate grass with a rapid life cycle and a small genome. It is a self-fertile plant that can be transformed with high efficiency using Agrobacteria and callus derived from immature embryos. In addition, considerable genetic and genomic resources are becoming available for this species in the form of mapping populations, large expressed sequence tag collections, T-DNA insertion lines and, in the near future, the complete genome sequence. The development of Brachypodium as a model species is of particular value in the areas of cell wall and biomass research, where differences between dicots and grasses are greatest. Here we explore the effect of mild conditions of pretreatment and hydrolysis in Brachypodium stem segments as a contribution for the establishment of sensitive screening of the saccharification properties in different genetic materials.

Results
The non-cellulosic monosaccharide composition of Brachypodium is closely related to grasses of agricultural importance and significantly different from the dicot model Arabidopsis thaliana. Diluted acid pretreatment of stem segments produced significant release of sugars and negatively affected the amount of sugars obtained by enzymatic hydrolysis. Monosaccharide and oligosaccharide analysis showed that the hemicellulose fraction is the main target of the enzymatic activity under the modest hydrolytic conditions used in our assays. Scanning electron microscopy analysis of the treated materials showed progressive exposure of fibrils in the stem segments.

Conclusion
Results presented here indicate that under mild conditions cellulose and hemicellulose are hydrolysed to differing extents, with hemicellulose hydrolysis predominating. We anticipate that the sub-optimal conditions for hydrolysis identified here will provide a sensitive assay to detect variations in saccharification among Brachypodium plants, providing a useful analytical tool for identifying plants with alterations in this trait.
Gene expression analysis of glioblastomas identifies the major molecular basis for the prognostic benefit of younger age
Authors: Lee Yohan , Scheck Adrienne C , Cloughesy Timothy F , Lai Albert , Dong Jun , Farooqi Haumith K , Liau Linda M , Horvath Steve , Mischel Paul S , Nelson Stanley F 
Published: October 2008

Abstract

Background
Glioblastomas are the most common primary brain tumour in adults. While the prognosis for patients is poor, gene expression profiling has detected signatures that can sub-classify GBMs relative to histopathology and clinical variables. One category of GBM defined by a gene expression signature is termed ProNeural (PN), and has substantially longer patient survival relative to other gene expression-based subtypes of GBMs. Age of onset is a major predictor of the length of patient survival where younger patients survive longer than older patients. The reason for this survival advantage has not been clear.

Methods
We collected 267 GBM CEL files and normalized them relative to other microarrays of the same Affymetrix platform. 377 probesets on U133A and U133 Plus 2.0 arrays were used in a gene voting strategy with 177 probesets of matching genes on older U95Av2 arrays. Kaplan-Meier curves and Cox proportional hazard analyses were applied in distinguishing survival differences between expression subtypes and age.

Results
This meta-analysis of published data in addition to new data confirms the existence of four distinct GBM expression-signatures. Further, patients with PN subtype GBMs had longer survival, as expected. However, the age of the patient at diagnosis is not predictive of survival time when controlled for the PN subtype.

Conclusion
The survival benefit of younger age is nullified when patients are stratified by gene expression group. Thus, the main cause of the age effect in GBMs is the more frequent occurrence of PN GBMs in younger patients relative to older patients.
Effect of the rs997509 Polymorphism on the Association between Ectonucleotide Pyrophosphatase Phosphodiesterase 1 and Metabolic Syndrome and Impaired Glucose Tolerance in Childhood Obesity
Authors: Santoro Nicola , Cirillo Grazia , Lepore Maria Grazia , Palma Alfonsina , Amato Alessandra , Savarese Piera , Marzuillo Pierluigi , Grandone Anna , Perrone Laura , del Giudice Emanuele Miraglia 
Published: October 2008

Abstract
Context: Variants on the nucleotide pyrophosphatase/phosphodiesterase-1 (ENPP-1) gene have been associated with obesity and insulin resistance. Because insulin resistance is a pivotal factor in the development of metabolic syndrome (MS) and impaired glucose tolerance (IGT), we aimed to test the association between the K121Q and rs997509 ENPP-1 variants with obesity, MS and IGT in obese children and adolescents.
Methods: We screened 809 children, 409 obese and 400 lean controls. Obese subjects underwent a standard oral glucose tolerance test, whole body insulin sensitivity index (WBISI) and homeostasis model assessment (HOMA) were calculated.
Results: No difference in prevalence for K121Q and rs997509 polymorphisms between obese and controls (P &gt; 0.05) were observed. Obese children carrying the rs997509 rare allele showed higher insulin (P = 0.001), HOMA (P &lt; .001) and lower WBISI values (P = 0.04) compared with common allele homozygous. A similar observation was done for K121Q variant, with 121Q allele carriers showing higher insulin (P = 0.03) and HOMA (P = 0.04) values than 121K homozygotes. Moreover, subjects carrying the rs997509 rare allele had higher risk of MS (odds ratio 2.4, 95% confidence interval: 1.3–4.3) and IGT (odds ratio 4.7, 95% confidence interval: 1.9–11.4) than common allele homozygotes. Evaluating combined effects of both polymorphisms, which are in strong linkage disequilibrium, we showed that the effect on insulin sensitivity was due to the rs997509 T variant.
Conclusion: We conclude that the ENPP1 rs997509T allele can predispose obese children to MS and IGT and that this variant might drive the association between the ENPP1 121Q allele and insulin resistance.
Convective heat dissipation from a wheel-hub-mounted railway brake disc
Authors: Tirovic M , Galindo-Lopez C H 
Published: October 2008

Air flow and convective heat dissipation from a wheel-hub-mounted railway brake disc were studied using computational fluid dynamics (CFD). The analyses enabled detailed insight into air flow, temperature, speed, pressure, and convective heat transfer coefficient distributions, never before available to a brake designer. Such results are practically impossible to experimentally obtain at reasonable cost. Particularly interesting finding is the existence of relatively considerable secondary flow — circumferential flow behind the vanes. Although this effect may reduce air pumping, and therefore radial air speed, it increases turbulence by promoting airflow between channels. Average values of the convective heat transfer coefficients obtained using CFD are practically identical to the experimental values derived from cooling tests performed on dynamometer and spin rig. Compared with other railway disc designs, this disc demonstrates exceptionally good convective cooling characteristics, in particular considering its size and investigated operating condition (rotation in still air). The computational studies of air flow and heat dissipation characteristics are an excellent base for development work in improving existing and generating new disc designs with high heat dissipation characteristics. Future work is concentrated on conducting additional analyses of the current disc design, in order to investigate the most effective ways of maximizing convective cooling.
Modelling of the dynamic behaviour of in situ concrete railway sleepers
Authors: Dahlberg T 
Published: October 2008

An analytical solution to the problem of a vibrating beam on an elastic foundation is presented. An application example of a concrete railway sleeper embedded in an elastic medium (the ballast) is provided. The sleeper is also elastically connected to the rails. The Rayleigh—Timoshenko (R—T) beam theory for a beam on an elastic foundation is used and eigenfrequencies are calculated. The beam (sleeper) is divided into three sections that have piecewise constant properties. The central portion of the beam is slightly thinner than the outer parts, and each one of the three parts may or may not be supported by the elastic foundation. The elastic connections to the rails are situated at the two joinings of the three sleeper sections. Conclusions drawn are that the Euler—Bernoulli beam theory can be used to calculate two, or maximum three, eigenfrequencies of the sleeper. For higher frequencies, the R—T beam theory should be used. The foundation stiffness influences the lowest bending-mode eigenfrequency the most; higher eigenfrequencies are practically unaffected by the foundation stiffness. The influence of railpad (and rail) stiffness on the sleeper eigenfrequencies is negligible.
A review on non-destructive evaluation of rails: State-of-the-art and future development
Authors: Ph Papaelias M , Roberts C , Davis C L 
Published: October 2008

Rails are systematically inspected for internal and surface defects using various non-destructive evaluation (NDE) techniques. During the manufacturing process, rails are inspected using automated optical cameras and eddy current sensing systems for any surface damage, while the presence of internal defects is assessed through ultrasonic inspection. Similarly, ultrasonic transducers and magnetic induction sensors have been extensively used by the rail industry for the inspection of rails in-service. More recently, automated vision techniques and hybrid systems based on the simultaneous use of pulsed eddy current probes and conventional ultrasonic probes have been introduced for the high-speed inspection of rail tracks. Other NDE techniques, such as electromagnetic acoustic transducers, laser ultrasonics, guided waves, and alternating current field measurement probes, are also under development for application in the rail industry. This paper comprehensively reviews NDE methodologies in use around Europe and North America for rail defect detection. This includes a detailed overview of the background theory and the techniques used to incorporate condition data into maintenance procedures. It also presents a review of the current state-of-the-art in NDE of railways coupled with a discussion of future developments and novel inspection methodologies in the field.