bluuebunny/crossref_metadata_2025_split huggingface dataset:
The small GTPase Ral mediates SDF-1–induced migration of B cells and multiple myeloma cells
Authors: de Gorter David J. J. , Reijmers Rogier M. , Beuling Esther A. , Naber Hildegonda P. H. , Kuil Annemieke , Kersten Marie José , Pals Steven T. , Spaargaren Marcel 
Published: January 2008

AbstractChemokine-controlled migration plays a critical role in B-cell development, differentiation, and function, as well as in the pathogenesis of B-cell malignancies, including the plasma cell neoplasm multiple myeloma (MM). Here, we demonstrate that stimulation of B cells and MM cells with the chemokine stromal cell–derived factor-1 (SDF-1) induces strong migration and activation of the Ras-like GTPase Ral. Inhibition of Ral, by expression of the dominant negative RalN28 mutant or of RalBPΔGAP, a Ral effector mutant that sequesters active Ral, results in impaired SDF-1–induced migration of B cells and MM cells. Of the 2 Ral isoforms, RalA and RalB, RalB was found to mediate SDF-1–induced migration. We have recently shown that Btk, PLCγ2, and Lyn/Syk mediate SDF-1–controlled B-cell migration; however, SDF-1–induced Ral activation is not affected in B cells deficient in these proteins. In addition, treatment with pharmacological inhibitors against PI3K and PLC or expression of dominant-negative Ras did not impair SDF-1–induced Ral activation. Taken together, these results reveal a novel function for Ral, that is, regulation of SDF-1–induced migration of B cells and MM cells, thereby providing new insights into the control of B-cell homeostasis, trafficking, and function, as well as into the pathogenesis of MM.
Validation of protein models by a neural network approach
Authors: Mereghetti Paolo , Ganadu Maria Luisa , Papaleo Elena , Fantucci Piercarlo , De Gioia Luca 
Published: January 2008

Abstract

Background
The development and improvement of reliable computational methods designed to evaluate the quality of protein models is relevant in the context of protein structure refinement, which has been recently identified as one of the bottlenecks limiting the quality and usefulness of protein structure prediction.

Results
In this contribution, we present a computational method (Artificial Intelligence Decoys Evaluator: AIDE) which is able to consistently discriminate between correct and incorrect protein models. In particular, the method is based on neural networks that use as input 15 structural parameters, which include energy, solvent accessible surface, hydrophobic contacts and secondary structure content. The results obtained with AIDE on a set of decoy structures were evaluated using statistical indicators such as Pearson correlation coefficients, Z
nat
, fraction enrichment, as well as ROC plots. It turned out that AIDE performances are comparable and often complementary to available state-of-the-art learning-based methods.

Conclusion
In light of the results obtained with AIDE, as well as its comparison with available learning-based methods, it can be concluded that AIDE can be successfully used to evaluate the quality of protein structures. The use of AIDE in combination with other evaluation tools is expected to further enhance protein refinement efforts.
Evaluation of two methods for computational HLA haplotypes inference using a real dataset
Authors: Bettencourt Bruno F , Santos Margarida R , Fialho Raquel N , Couto Ana R , Peixoto Maria J , Pinheiro João P , Spínola Hélder , Mora Marian G , Santos Cristina , Brehm António , Bruges-Armas Jácome 
Published: January 2008

AbstractBackgroundHLA haplotype analysis has been used in population genetics and in the investigation of disease-susceptibility locus, due to its high polymorphism. Several methods for inferring haplotype genotypic data have been proposed, but it is unclear how accurate each of the methods is or which method is superior. The accuracy of two of the leading methods of computational haplotype inference – Expectation-Maximization algorithm based (implemented in Arlequin V3.0) and Bayesian algorithm based (implemented in PHASE V2.1.1) – was compared using a set of 122 HLA haplotypes (A-B-Cw-DQB1-DRB1) determined through direct counting. The accuracy was measured with the Mean Squared Error (MSE), Similarity Index (IF) and Haplotype Identification Index (IH).ResultsNone of the methods inferred all of the known haplotypes and some differences were observed in the accuracy of the two methods in terms of both haplotype determination and haplotype frequencies estimation. Working with haplotypes composed by low polymorphic sites, present in more than one individual, increased the confidence in the assignment of haplotypes and in the estimation of the haplotype frequencies generated by both programs.ConclusionThe PHASE v2.1.1 implemented method had the best overall performance both in haplotype construction and frequency calculation, although the differences between the two methods were insubstantial. To our knowledge this was the first work aiming to test statistical methods using real haplotypic data from the HLA region.
Cheiradone: a vascular endothelial cell growth factor receptor antagonist
Authors: Hussain Sajjad , Slevin Mark , Mesaik Mohammad A , Choudhary Mohammad I , Elosta Abdul H , Matou Sabine , Ahmed Nessar , West David , Gaffney John 
Published: January 2008

Abstract

Background
Angiogenesis, the growth of new blood vessels from the pre-existing vasculature is associated with physiological (for example wound healing) and pathological conditions (tumour development). Vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2) and epidermal growth factor (EGF) are the major angiogenic regulators. We have identified a natural product (cheiradone) isolated from a Euphorbia species which inhibited in vivo and in vitro VEGF- stimulated angiogenesis but had no effect on FGF-2 or EGF activity. Two primary cultures, bovine aortic and human dermal endothelial cells were used in in vitro (proliferation, wound healing, invasion in Matrigel and tube formation) and in vivo (the chick chorioallantoic membrane) models of angiogenesis in the presence of growth factors and cheiradone. In all cases, the concentration of cheiradone which caused 50% inhibition (IC50) was determined. The effect of cheiradone on the binding of growth factors to their receptors was also investigated.

Results
Cheiradone inhibited all stages of VEGF-induced angiogenesis with IC50 values in the range 5.20–7.50 μM but did not inhibit FGF-2 or EGF-induced angiogenesis. It also inhibited VEGF binding to VEGF receptor-1 and 2 with IC50 values of 2.9 and 0.61 μM respectively.

Conclusion
Cheiradone inhibited VEGF-induced angiogenesis by binding to VEGF receptors -1 and -2 and may be a useful investigative tool to study the specific contribution of VEGF to angiogenesis and may have therapeutic potential.
A process for analysis of microarray comparative genomics hybridisation studies for bacterial genomes
Authors: Carter Ben , Wu Guanghui , Woodward Martin J , Anjum Muna F 
Published: January 2008

Abstract

Background
Microarray based comparative genomic hybridisation (CGH) experiments have been used to study numerous biological problems including understanding genome plasticity in pathogenic bacteria. Typically such experiments produce large data sets that are difficult for biologists to handle. Although there are some programmes available for interpretation of bacterial transcriptomics data and CGH microarray data for looking at genetic stability in oncogenes, there are none specifically to understand the mosaic nature of bacterial genomes. Consequently a bottle neck still persists in accurate processing and mathematical analysis of these data. To address this shortfall we have produced a simple and robust CGH microarray data analysis process that may be automated in the future to understand bacterial genomic diversity.

Results
The process involves five steps: cleaning, normalisation, estimating gene presence and absence or divergence, validation, and analysis of data from test against three reference strains simultaneously. Each stage of the process is described and we have compared a number of methods available for characterising bacterial genomic diversity, for calculating the cut-off between gene presence and absence or divergence, and shown that a simple dynamic approach using a kernel density estimator performed better than both established, as well as a more sophisticated mixture modelling technique. We have also shown that current methods commonly used for CGH microarray analysis in tumour and cancer cell lines are not appropriate for analysing our data.

Conclusion
After carrying out the analysis and validation for three sequenced Escherichia coli strains, CGH microarray data from 19 E. coli O157 pathogenic test strains were used to demonstrate the benefits of applying this simple and robust process to CGH microarray studies using bacterial genomes.
Metabolic and morphological alterations induced by proteolysis-inducing factor from Walker tumour-bearing rats in C2C12myotubes
Authors: Yano Claudia L , Ventrucci Gislaine , Field William N , Tisdale Michael J , Gomes-Marcondes Maria Cristina C 
Published: January 2008

Abstract

Background
Patients with advanced cancer suffer from cachexia, which is characterised by a marked weight loss, and is invariably associated with the presence of tumoral and humoral factors which are mainly responsible for the depletion of fat stores and muscular tissue.

Methods
In this work, we used cytotoxicity and enzymatic assays and morphological analysis to examine the effects of a proteolysis-inducing factor (PIF)-like molecule purified from ascitic fluid of Walker tumour-bearing rats (WF), which has been suggested to be responsible for muscle atrophy, on cultured C2C12 muscle cells.

Results
WF decreased the viability of C2C12 myotubes, especially at concentrations of 20–25 μg.mL-1. There was an increase in the content of the pro-oxidant malondialdehyde, and a decrease in antioxidant enzyme activity. Myotubes protein synthesis decreased and protein degradation increased together with an enhanced in the chymotrypsin-like enzyme activity, a measure of functional proteasome activity, after treatment with WF. Morphological alterations such as cell retraction and the presence of numerous cells in suspension were observed, particularly at high WF concentrations.

Conclusion
These results indicate that WF has similar effects to those of proteolysis-inducing factor, but is less potent than the latter. Further studies are required to determine the precise role of WF in this experimental model.
Topical rapamycin inhibits tuberous sclerosis tumor growth in a nude mouse model
Authors: Rauktys Aubrey , Lee Nancy , Lee Laifong , Dabora Sandra L 
Published: January 2008

AbstractBackgroundSkin manifestations of Tuberous Sclerosis Complex (TSC) cause significant morbidity. The molecular mechanism underlying TSC is understood and there is evidence that systemic treatment with rapamycin or other mTOR inhibitors may be a useful approach to targeted therapy for the kidney and brain manifestations. Here we investigate topical rapamycin in a mouse model for TSC-related tumors.Methods0.4% and 0.8% rapamycin ointments were applied to nude mice bearing subcutaneous, TSC-related tumors. Topical treatments were compared with injected rapamycin and topical vehicle. Rapamycin levels in blood and tumors were measured to assess systemic drug levels in all cohorts.ResultsTreatment with topical rapamycin improved survival and reduced tumor growth. Topical rapamycin treatment resulted in systemic drug levels within the known therapeutic range and was not as effective as injected rapamycin.ConclusionTopical rapamycin inhibits TSC-related tumor growth. These findings could lead to a novel treatment approach for facial angiofibromas and other TSC skin lesions.
Generation of functional scFv intrabody to abate the expression of CD147 surface molecule of 293A cells
Authors: Tragoolpua Khajornsak , Intasai Nutjeera , Kasinrerk Watchara , Mai Sabine , Yuan Yuan , Tayapiwatana Chatchai 
Published: January 2008

AbstractBackgroundExpression of intracellular antibodies (intrabodies) has become a broadly applicable technology for generation of phenotypic knockoutsin vivo. The method uses surface depletion of cellular membrane proteins to examine their biological function. In this study, we used this strategy to block the transport of cell surface molecule CD147 to the cell membrane. Phage display technology was introduced to generate the functional antibody fragment to CD147, and we subsequently constructed a CD147-specific scFv that was expressed intracellularly and retained in the endoplasmic reticulum by adenoviral gene transfer.ResultsThe recombinant antibody fragments, Fab and scFv, of the murine monoclonal antibody (clone M6-1B9) reacted specifically to CD147 by indirect enzyme-linked immunosorbent assays (ELISA) using a recombinant CD147-BCCP as a target. This indicated that the Fab- and scFv-M6-1B9 displaying on phage surfaces were correctly folded and functionally active. We subsequently constructed a CD147-specific scFv, scFv-M6-1B9-intrabody, in 293A cells. The expression of CD147 on 293A cell surface was monitored at 36 h after transduction by flow cytometry and demonstrated remarkable reduction. Colocalization of scFv-M6-1B9 intrabody with CD147 in the ER network was depicted using a 3D deconvolution microscopy system.ConclusionThe results suggest that our approach can generate antibody fragments suitable for decreasing the expression of CD147 on 293A cells. This study represents a step toward understanding the role of the cell surface protein, CD147.
Clinical Ethics Consultation: Examining how American and Japanese experts analyze an Alzheimer's case
Authors: Nagao Noriko , Aulisio Mark P , Nukaga Yoshio , Fujita Misao , Kosugi Shinji , Youngner Stuart , Akabayashi Akira 
Published: January 2008

Abstract

Background
Few comparative studies of clinical ethics consultation practices have been reported. The objective of this study was to explore how American and Japanese experts analyze an Alzheimer's case regarding ethics consultation.

Methods
We presented the case to physicians and ethicists from the US and Japan (one expert from each field from both countries; total = 4) and obtained their responses through a questionnaire and in-depth interviews.

Results
Establishing a consensus was a common goal among American and Japanese participants. In attempting to achieve consensus, the most significant similarity between Japanese and American ethics consultants was that they both appeared to adopt an "ethics facilitation" approach. Differences were found in recommendation and assessment between the American and Japanese participants. In selecting a surrogate, the American participants chose to contact the grandson before designating the daughter-in-law as the surrogate decision-maker. Conversely the Japanese experts assumed that the daughter-in-law was the surrogate.

Conclusion
Our findings suggest that consensus building through an "ethics facilitation" approach may be a commonality to the practice of ethics consultation in the US and Japan, while differences emerged in terms of recommendations, surrogate assessment, and assessing treatments. Further research is needed to appreciate differences not only among different nations including, but not limited to, countries in Europe, Asia and the Americas, but also within each country.
A new evaluation method for +Gz tolerance with loratadine by using a near-infrared spectroscopy
Authors: Onozawa Akihiko , Kikukawa Azusa , Miyamoto Yoshinori 
Published: January 2008

Abstract

Background
Loratadine (Claritin®), an over the counter antihistamine in U.S. and UK, is acceptable for use without adverse side effects by aircrew with mild or moderate allergic or other situations requiring an antihistamine. Although +Gz (head to foot direction) tolerance testing for aircrew with loratadine has not been documented in the published literature, it is commonly accepted that loratadine dose not effect +Gz tolerance. The purpose of this study was to offer and validate a new evaluation method for +Gz tolerance testing with loratadine by using a near-infrared spectroscopy (NIRS).

Methods
A double-blind, placebo-controlled, randomized, crossover protocol was used to administer 10 mg of loratadine or placebo in nine healthy subjects. The subjects didn't wear anti-G suit. The +Gz exposure profiles consisted of, in series, a gradual onset ran (0.1 G·sec-1) to the subject's visual end-point (peripheral light loss) or loss of consciousness (GLOC), and rapid onset run (1.0 G·sec-1) to the subject's same end-point. In this study, G-level tolerance was defined as the +Gz level at visual end-point and/or at GLOC. As a subject's G-duration tolerance, we measured the total time (seconds) during rapid onset run. Otherwise, to confirm the effect of loratadine on +Gz tolerance, we measured the cerebral NIRS variables (hemoglobin concentration changes and tissue oxygenation index) as a new quantitative method for +Gz tolerance during a centrifuge experiments.

Results
No significant differences were observed in +Gz tolerance (+Gz level, duration time and NIRS variables) between subjects taking loratadine and placebo.

Conclusion
Our results demonstrate that loratadine has no detectable effect on +Gz tolerance by using a new method with cerebral NIRS variables and the traditional method with +Gz level and duration time. This study represents the first use of a quantitative parameter such as cerebral NIRS variables to assess the effects of a drug on acceleration tolerance.
Reliability and relative validity of a child nutrition questionnaire to simultaneously assess dietary patterns associated with positive energy balance and food behaviours, attitudes, knowledge and environments associated with healthy eating
Authors: Wilson Annabelle M , Magarey Anthea M , Mastersson Nadia 
Published: January 2008

AbstractBackgroundFood behaviours, attitudes, environments and knowledge are relevant to professionals in childhood obesity prevention, as are dietary patterns which promote positive energy balance. There is a lack of valid and reliable tools to measure these parameters. The aim of this study was to determine the reliability and relative validity of a child nutrition questionnaire assessing all of these parameters, used in the evaluation of a community-based childhood obesity prevention project.MethodsThe development of the 14-item questionnaire was informed by the aims of the obesity prevention project. A sub-sample of children aged 10–12 years from primary schools involved in the intervention was recruited at the project's baseline data collection (Test 1). Questionnaires were readministered (Test 2) following which students completed a 7-day food diary designed to reflect the questionnaire. Twelve scores were derived to assess consumption of fruit, vegetables, water, noncore foods and sweetened beverages plus food knowledge, behaviours, attitudes and environments. Reliability was assessed using (a) the intra class correlation coefficient (ICC) and 95% confidence intervals to compare scores from Tests 1 and 2 (test-retest reliability) and (b) Cronbach's alpha (internal consistency). Validity was assessed with Spearman correlations, bias and limits of agreement between scores from Test 1 and the 7-day diaries. The Wilcoxon signed rank test checked for significant differences between mean scores.ResultsOne hundred and forty one students consented to the study. Test 2 (n = 134) occurred between eight and 36 days after Test 1. For 10/12 scores ICCs ranged from 0.47–0.66 (p < 0.001) while for two scores ICCs were < 0.4 (p < 0.05). Spearman correlations ranged from 0.34–0.48 (p < 0.01) and Cronbach's alpha 0.50–0.80. Three scores were modified based on this analysis. The Wilcoxon signed rank test found no evidence of a difference between means (p > 0.05) for 10/12 (test-retest reliability) and 3/7 (validity) scores.ConclusionThis child nutrition questionnaire is a valid and reliable tool to simultaneously assess dietary patterns associated with positive energy balance, and food behaviours, attitudes and environments in Australian school children aged 10–12 years. Thus it can be used to monitor secular changes in these parameters and measure the effectiveness of this and other obesity prevention projects with similar aims.
Learning from positive examples when the negative class is undetermined- microRNA gene identification
Authors: Yousef Malik , Jung Segun , Showe Louise C , Showe Michael K 
Published: January 2008

Abstract

Background
The application of machine learning to classification problems that depend only on positive examples is gaining attention in the computational biology community. We and others have described the use of two-class machine learning to identify novel miRNAs. These methods require the generation of an artificial negative class. However, designation of the negative class can be problematic and if it is not properly done can affect the performance of the classifier dramatically and/or yield a biased estimate of performance. We present a study using one-class machine learning for microRNA (miRNA) discovery and compare one-class to two-class approaches using naïve Bayes and Support Vector Machines. These results are compared to published two-class miRNA prediction approaches. We also examine the ability of the one-class and two-class techniques to identify miRNAs in newly sequenced species.

Results
Of all methods tested, we found that 2-class naive Bayes and Support Vector Machines gave the best accuracy using our selected features and optimally chosen negative examples. One class methods showed average accuracies of 70–80% versus 90% for the two 2-class methods on the same feature sets. However, some one-class methods outperform some recently published two-class approaches with different selected features. Using the EBV genome as and external validation of the method we found one-class machine learning to work as well as or better than a two-class approach in identifying true miRNAs as well as predicting new miRNAs.

Conclusion
One and two class methods can both give useful classification accuracies when the negative class is well characterized. The advantage of one class methods is that it eliminates guessing at the optimal features for the negative class when they are not well defined. In these cases one-class methods can be superior to two-class methods when the features which are chosen as representative of that positive class are well defined.

Availability
The OneClassmiRNA program is available at: [1]
Computational discovery of cis-regulatory modules in Drosophila without prior knowledge of motifs
Authors: Ivan Andra , Halfon Marc S , Sinha Saurabh 
Published: January 2008

AbstractWe consider the problem of predicting cis-regulatory modules without knowledge of motifs. We formulate this problem in a pragmatic setting, and create over 30 new data sets, using Drosophila modules, to use as a 'benchmark'. We propose two new methods for the problem, and evaluate these, as well as two existing methods, on our benchmark. We find that the challenge of predicting cis-regulatory modules ab initio, without any input of relevant motifs, is a realizable goal.