bluuebunny/crossref_metadata_2025_split huggingface dataset:
Accounting for loop flexibility during protein–protein docking
Authors: Bastard Karine , Prévost Chantal , Zacharias Martin 
Published: December 2005

AbstractAlthough reliable docking can now be achieved for systems that do not undergo important induced conformational change upon association, the presence of flexible surface loops, which must adapt to the steric and electrostatic properties of a partner, generally presents a major obstacle. We report here the first docking method that allows large loop movements during a systematic exploration of the possible arrangements of the two partners in terms of position and rotation. Our strategy consists in taking into account an ensemble of possible loop conformations by a multi‐copy representation within a reduced protein model. The docking process starts from regularly distributed positions and orientations of the ligand around the whole receptor. Each starting configuration is submitted to energy minimization during which the best‐fitting loop conformation is selected based on the mean‐field theory. Trials were carried out on proteins with significant differences in the main‐chain conformation of the binding loop between isolated form and complexed form, which were docked to their partner considered in their bound form. The method is able to predict complexes very close to the crystal complex both in terms of relative position of the two partners and of the geometry of the flexible loop. We also show that introducing loop flexibility on the isolated protein form during systematic docking largely improves the predictions of relative position of the partners in comparison with rigid‐body docking. Proteins 2006. © 2005 Wiley‐Liss, Inc.
A Numerical Investigation of Heat Transfer Cardiac Output Measurements
Authors: Fotheringham P. , Gourlay A. R. , Mckee S. , Andrews S. 
Published: December 2005

Measurement of cardiac output is often investigated using a technique based on hot‐film anemometry. Here, we discuss a modification to hot‐film anemometry, which involves a cylindrical heating element mounted flush on the surface of a typical Swan‐Ganz catheter. In contrast to traditional thermodilution, the method discussed here has the potential to allow continuous monitoring of cardiac output.This paper demonstrates that there is a simple approximate relationship between the power input to the device to maintain a temperature of one degree above blood heat and cardiac output. Since, the heat transfer and the fluid flow decouple, a numerical model of the heat transfer of a cylindrical catheter (with heating element) sitting concentrically within a rigid cylindrical artery is developed. Numerical results were obtained for a wide selection of flow profiles, including experimental data. The results indicate that the cardiac output/power input relationship is extremely robust with respect to flow profile and system parameter variation.
Accurate prediction of HIV-1 drug response from the reverse transcriptase and protease amino acid sequences using sparse models created by convex optimization
Authors: Rabinowitz Matthew , Myers Lance , Banjevic Milena , Chan Albert , Sweetkind-Singer Joshua , Haberer Jessica , McCann Kelly , Wolkowicz Roland 
Published: December 2005

AbstractMotivation: Genotype–phenotype modeling problems are often overcomplete, or ill-posed, since the number of potential predictors—genes, proteins, mutations and their interactions—is large relative to the number of measured outcomes. Such datasets can still be used to train sparse parameter models that generalize accurately, by exerting a principle similar to Occam's Razor: When many possible theories can explain the observations, the most simple is most likely to be correct. We apply this philosophy to modeling the drug response of Type-1 Human Immunodeficiency Virus (HIV-1). Owing to the decreasing expense of genetic sequencing relative to in vitro phenotype testing, a statistical model that reliably predicts viral drug response from genetic data is an important tool in the selection of antiretroviral therapy (ART). The optimization techniques described will have application to many genotype–phenotype modeling problems for the purpose of enhancing clinical decisions.Results: We describe two regression techniques for predicting viral phenotype in response to ART from genetic sequence data. Both techniques employ convex optimization for the continuous subset selection of a sparse set of model parameters. The first technique, the least absolute shrinkage and selection operator, uses the l1 norm loss function to create a sparse linear model; the second, the support vector machine with radial basis kernel functions, uses the ε-insensitive loss function to create a sparse non-linear model. The techniques are applied to predict the response of the HIV-1 virus to 10 reverse transcriptase inhibitor and 7 protease inhibitor drugs. The genetic data are derived from the HIV coding sequences for the reverse transcriptase and protease enzymes. When tested by cross-validation with actual laboratory measurements, these models predict drug response phenotype more accurately than models previously discussed in the literature, and other canonical techniques described here. Key features of the methods that enable this performance are the tendency to generate simple models where many of the parameters are zero, and the convexity of the cost function, which assures that we can find model parameters to globally minimize the cost function for a particular training dataset.Availability: Results, tables and figures are available atContact: mrabinowitz@genesecurity.netSupplementary information: An Appendix to accompany this article is available at Bioinformatics online.
Multidimensional local false discovery rate for microarray studies
Authors: Ploner Alexander , Calza Stefano , Gusnanto Arief , Pawitan Yudi 
Published: December 2005

AbstractMotivation: The false discovery rate (fdr) is a key tool for statistical assessment of differential expression (DE) in microarray studies. Overall control of the fdr alone, however, is not sufficient to address the problem of genes with small variance, which generally suffer from a disproportionally high rate of false positives. It is desirable to have an fdr-controlling procedure that automatically accounts for gene variability.Methods: We generalize the local fdr as a function of multiple statistics, combining a common test statistic for assessing DE with its standard error information. We use a non-parametric mixture model for DE and non-DE genes to describe the observed multi-dimensional statistics, and estimate the distribution for non-DE genes via the permutation method. We demonstrate this fdr2d approach for simulated and real microarray data.Results: The fdr2d allows objective assessment of DE as a function of gene variability. We also show that the fdr2d performs better than commonly used modified test statistics.Availability: An R-package OCplus containing functions for computing fdr2d() and other operating characteristics of microarray data is available atContact: alexander.ploner@meb.ki.se
Local RNA base pairing probabilities in large sequences
Authors: Bernhart Stephan H. , Hofacker Ivo L. , Stadler Peter F. 
Published: December 2005

Abstract
Summary: The genome-wide search for non-coding RNAs requires efficient methods to compute and compare local secondary structures. Since the exact boundaries of such putative transcripts are typically unknown, arbitrary sequence windows have to be used in practice. Here we present a method for robustly computing the probabilities of local base pairs from long RNA sequences independent of the exact positions of the sequence window.
Availability: The program RNAplfold is part of the Vienna RNA Package and can be downloaded from
Contact: ivo@tbi.univie.ac.at
Self‐Rated Health and Risk Factors for Metabolic Syndrome Among Middle‐Aged Men
Authors: Näslindh‐Ylispangar Anita , Sihvonen Marja , Vanhanen Hannu , Kekki Pertti 
Published: December 2005

Abstract
Objectives:
To examine lifestyle and clinical risk factors for metabolic syndrome (MBO) and compare their significance between levels of self‐rated health among middle‐aged men. Design: A cross‐sectional baseline study. Sample: 273 men, aged 40, living in Helsinki, Finland. Methods: Postal questionnaires and health examinations by public health nurses were used in data collection. Statistical differences between groups of self‐rated health and risk factors were analyzed by chi‐square tests. Results: Of all the respondents, 55% rated their health as good and 45% as average. Two thirds were overweight or obese, and 35% had waist‐hip ratio more than 100 cm. Approximately 43% had diastolic blood pressure greater than 90 mmHg. Over half of the men smoked daily, and 28% used alcohol excessively. Conclusions: The men in this sample were found to be at high risk of developing MBO. The results underscore the importance of understanding the contradiction that exists between subjective and objective health ratings. Public health nurses are in a key position to educate men on how to use simple measurements to objectively assess their risk factors and, thus, potentially reduce their risk of developing diabetes, heart attack, or stroke.
Gastric and intestinal phenotypes and histogenesis of advanced glandular stomach cancers in carcinogen‐treated, Helicobacter pylori‐infected Mongolian gerbils
Authors: Mizoshita Tsutomu , Tsukamoto Tetsuya , Takenaka Yoshiharu , Cao Xueyuan , Kato Sosuke , Kaminishi Michio , Tatematsu Masae 
Published: December 2005

The Helicobacter pylori‐infected Mongolian gerbil (MG) has been established as an appropriate animal model for studies of stomach cancer development. However, there have hitherto been no data on the phenotypic classification of glandular stomach cancers in H. pylori‐infected and non‐infected MG. We therefore examined the phenotypes of 50 and six advanced glandular stomach cancers in H. pylori‐infected and non‐infected MG, respectively, as well as adjacent non‐neoplastic mucosa, using several gastrointestinal epithelial phenotypic markers. The lesions were divided phenotypically into 21 gastric, 24 gastric‐and‐intestinal mixed, four intestinal and one null types, with 90.0% of the lesions harboring gastric elements and 56.0% demonstrating intestinal phenotypic expression in H. pylori‐infected MG. All six lesions were classified as gastric type in non‐infected MG. There was no clear correlation with the presence of intestinal metaplasia in surrounding mucosa. In conclusion, our data suggest that most advanced adenocarcinomas retain a gastric cellular phenotype in the glandular MG stomach. Thus, it might be proposed that intestinal metaplasia is a paracancerous phenomenon rather than a premalignant condition. H. pylori infection may trigger intestinalization of both stomach cancers and non‐neoplastic mucosa. (Cancer Sci 2006; 97: 38 – 44)
Chemical genomic screening for methylation‐silenced genes in gastric cancer cell lines using 5‐aza‐2′‐deoxycytidine treatment and oligonucleotide microarray
Authors: Yamashita Satoshi , Tsujino Yoshimi , Moriguchi Kazuki , Tatematsu Masae , Ushijima Toshikazu 
Published: December 2005

To identify novel methylation‐silenced genes in gastric cancers, we carried out a chemical genomic screening, a genome‐wide search for genes upregulated by treatment with a demethylating agent, 5‐aza‐2′‐deoxycytidine (5‐aza‐dC). After 5‐aza‐dC treatment of a gastric cancer cell line (AGS) 579 genes were upregulated 16‐fold or more, using an oligonucleotide microarray with 39 000 genes. From these genes, we selected 44 known genes on autosomes whose silencing in gastric cancer has not been reported. Thirty‐two of these had CpG islands (CGI) in their putative promoter regions, and all of the CGI were methylated in AGS, giving an estimated number of 421 ± 75 (95% confidence interval) methylation‐silenced genes. Additionally, we analyzed the methylation status of 16 potential tumor‐related genes with promoter CGI that were upregulated four‐fold or more, and 14 of these were methylated in AGS. Methylation status of the 32 randomly selected and 16 potential tumor‐related genes was analyzed in 10 primary gastric cancers, and 42 genes (ABHD9, ADFP, ALDH1A3, ANXA5, AREG, BDNF, BMP7, CAV1, CDH2, CLDN3, CTSL, EEF1A2, F2R, FADS1, FSD1, FST, FYN, GPR54, GREM1, IGFBP3, IGFBP7, IRS2, KISS1, MARK1, MLF1, MSX1, MTSS1, NT5E, PAX6, PLAGL1, PLAU, PPIC, RBP4, RORA, SCRN1, TBX3, TFAP2C, TNFSF9, ULBP2, WIF1, ZNF177 and ZNF559) were methylated in at least one primary gastric cancer. A metastasis suppressor gene, MTSS1, was located in a genomic region with frequent loss of heterozygosity (8q22), and was expressed abundantly in the normal gastric mucosa, suggesting its role in gastric carcinogenesis. (Cancer Sci 2006; 97: 64 –71)
Strong HLA‐DR antigen expression on cancer cells relates to better prognosis of colorectal cancer patients: Possible involvement of c‐myc suppression by interferon‐γin situ
Authors: Matsushita Kazuyuki , Takenouchi Toshinao , Shimada Hideaki , Tomonaga Takeshi , Hayashi Hideki , Shioya Ayumi , Komatsu Aki , Matsubara Hisahiro , Ochiai Takenori 
Published: December 2005

Strong HLA‐DR antigen expression on cancer cells relates to better prognosis of colorectal cancer patients, although the precise mechanism is controversial. From an immunological point of view, HLA‐DR antigen, induced by interferon (IFN)‐γ, is required for tumor‐associated antigen recognition by CD4+ T cells. For instance, as reported previously, the expression of HLA‐DR antigen in normal colorectal epithelium immediately adjacent to cancer coincided significantly with the existence of IFN‐γ mRNA in the tissue. From another aspect, IFN‐γ has been revealed to suppress c‐myc expression in vivo through a stat1‐dependent mechanism, which is important for cell growth, cell cycle and chromosome instability. In the present study, strong HLA‐DR‐positive expression on cancer cells was significantly related to better prognosis for colorectal cancer patients. High IFN‐γ mRNA expression in situ indicated significantly less activation of c‐myc mRNA expression. Further, HLA‐DR antigen expression in cancer cells, as well as Dukes stages, was an independent factor for better long‐term survival by multivariate analysis. Taken together, IFN‐γ, which induces HLA‐DR antigens on the cell surface, also suppresses c‐myc expression in situ, and is a possible non‐immunological mechanism involved in the better long‐term survival of colorectal cancer patients. (Cancer Sci 2006; 97: 57– 63)
Japanese single nucleotide polymorphism database for 267 possible drug‐related genes
Authors: Iida Aritoshi , Saito Susumu , Sekine Akihiro , Takahashi Atsushi , Kamatani Naoyuki , Nakamura Yusuke 
Published: December 2005

To establish ‘personalized medicines’ that can provide the right drug at the appropriate dose for each individual patient on the basis of genetic background, we have been building the infrastructure for a Japanese single nucleotide polymorphism (SNP) database of the genes encoding various enzymes, transporters and receptors that are involved in the metabolism, transportation and action of drugs. We have so far screened a genomic region of 4068.3 kb, and identified a total of 7552 genetic variations, including 6733 SNP and 819 genetic variations of other types among 267 genes in Japanese populations. Interestingly, among the 212 non‐synonymous substitutions we found, six would be considered to be nonsense mutations. In this review, we focused on the molecular features of the non‐synonymous substitutions and insertion/deletion polymorphisms within coding regions detected in drug‐related gene loci. The database established in this study makes us confident of achieving one of our goals, which is establishment of personalized medicine. (Cancer Sci 2006; 97: 16–24)
Using the chicken genome sequence in the development and mapping of genetic markers in the turkey (Meleagris gallopavo)
Authors: Chaves L. D. , Knutson T. P. , Krueth S. B. , Reed K. M. 
Published: December 2005

SummaryThe efficacy of employing the chicken genome sequence in developing genetic markers and in mapping the turkey genome was studied. Eighty previously uncharacterized microsatellite markers were identified for the turkey using BLAST alignment to the chicken genome. The chicken sequence was then used to develop primers for polymerase chain reaction where the turkey sequence was either unavailable or insufficient. A total of 78 primer sets were tested for amplification and polymorphism in the turkey, and informative markers were genetically mapped. Sixty‐five (83%) amplified turkey genomic DNA, and 33 (42%) were polymorphic in the University of Minnesota/Nicholas Turkey Breeding Farms mapping families. All but one marker genetically mapped to the position predicted from the chicken genome sequence. These results demonstrate the usefulness of the chicken sequence for the development of genomic resources in other avian species.
Sequence diversity and rates of molecular evolution between sheep and cattle genes
Authors: Kijas J. W. , Menzies M. , Ingham A. 
Published: December 2005

SummaryExperiments that aim to identify genes of importance in sheep are currently inhibited by a paucity of genomic resources. One approach, therefore, is to exploit the wealth of data and associated capabilities becoming available for the bovine genome. Cross‐species application of microarrays and comparative sequencing to identify single nucleotide polymorphisms are two possibilities; however, both are dependant on the level of nucleotide sequence similarity between the two species. This study used 120 gene orthologues consisting of over 60 kb of aligned sequence to estimate the gene diversity between cattle and sheep. Less than 3% of protein‐coding nucleotide positions were found to be different, indicating that the prospect for successfully using cross‐species strategies is high. Substitution at synonymous sites ranged between 6.9 and 7.7% (± 0.3%), and was higher than at non‐synonymous sites (1.4–1.7 ± 0.1%). The relative rate test was used to determine whether the observed mutation rates were constant between the two lineages. While the rate at synonymous sites appeared constant, the rate at non‐synonymous sites was significantly higher within the caprinae lineage (sheep) when compared with bovinae (cattle; χ2 = 10.03; d.f. = 1, P < 0.01). This is the first demonstration that variable rates of molecular evolution may be present within the family Bovidae.
Genome‐wide identification of quantitative trait loci in a cross between Hampshire and Landrace I: carcass traits
Authors: Karlskov‐Mortensen P. , Bruun C. S. , Braunschweig M. H. , Sawera M. , Markljung E. , Enfält A. C. , Hedebro‐Velander I. , Josell Å. , Lindahl G. , Lundström K. , von Seth G. , Jørgensen C. B. , Andersson L. , Fredholm M. 
Published: December 2005

SummaryWe report the identification of quantitative trait loci (QTL) affecting carcass composition, carcass length, fat deposition and lean meat content using a genome scan across 462 animals from a combined intercross and backcross between Hampshire and Landrace pigs. Data were analysed using multiple linear regression fitting additive and dominance effects. This model was compared with a model including a parent‐of‐origin effect to spot evidence of imprinting. Several precisely defined muscle phenotypes were measured in order to dissect body composition in more detail. Three significant QTL were detected in the study at the 1% genome‐wide level, and twelve significant QTL were detected at the 5% genome‐wide level. These QTL comprise loci affecting fat deposition and lean meat content on SSC1, 4, 9, 10, 13 and 16, a locus on SSC2 affecting the ratio between weight of meat and bone in back and weight of meat and bone in ham and two loci affecting carcass length on SSC12 and 17. The well‐defined phenotypes in this study enabled us to detect QTL for sizes of individual muscles and to obtain information of relevance for the description of the complexity underlying other carcass traits.
Recurrent childhood anaplastic large cell lymphoma: a retrospective analysis of registered cases in Japan
Authors: Mori Tetsuya , Takimoto Tetsuya , Katano Naoyuki , Kikuchi Akira , Tabuchi Ken , Kobayashi Ryoji , Ayukawa Hiroshi , Kumagai Masa‐aki , Horibe Keizo , Tsurusawa Masahito 
Published: December 2005

SummaryThis report presents a retrospective study of 26 Japanese children with recurrent anaplastic large cell lymphoma. The first relapses were documented at a median of 10·5 months after the initial diagnosis. Twenty‐four patients achieved a second remission. After a median follow‐up period of 47 months, 18 patients are still alive: 15 patients are in second complete remission (CR), three patients are in third CR or later. The 5 year overall and relapse‐free survival rates were 61 ± 12% and 51 ± 12% respectively. The patients who received allogeneic haematopoietic stem cell transplantation during second CR showed a superior outcome to other patients.
Cellular folate vitamer distribution during and after correction of vitamin B12 deficiency: a case for the methylfolate trap
Authors: Smulders Y. M. , Smith D. E. C. , Kok R. M. , Teerlink T. , Swinkels D. W. , Stehouwer C. D. A. , Jakobs C. 
Published: December 2005

SummaryHaematological sequellae of vitamin B12 deficiency are attributed to disturbed DNA synthesis, but vitamin B12 itself plays no role in DNA biosynthesis. A proposed explanation for this is the methylfolate trap hypothesis. This hypothesis states that B12 deficiency impairs overall folate metabolism because 5‐methyltetrahydrofolate (5MTHF) becomes metabolically trapped. This trap results from the fact that 5MTHF can neither be metabolised via the methionine synthase pathway, nor can it be reconverted to its precursor, methylenetetrahydrofolate. Other manifestations of the methylfolate trap include cellular folate loss because of shorter 5MTHF polyglutamate chains and global hypomethylation. The methylfolate trap has never been demonstrated in humans. We describe a patient with B12 deficiency who was homozygous for the common methylenetetrahydrofolate reductase (MTHFR) C677T mutation. We analysed red blood cell (RBC) folate vitamers and global DNA methylation by liquid chromatography (LC) in combination with tandem mass spectrometry, and 5MTHF polyglutamate length by LC‐electrochemical detection. Compared to post‐B12 supplementation values, homocysteine was higher (52·9 μmol/l vs. 16·8 μmol/l), RBC folate was lower (268·92 nmol/l vs. 501·2 nmol/l), the 5MTHF fraction of RBC folate was much higher (94·5% vs. 67·4%), polyglutamate chain length was shorter (more tetra‐ and pentaglutamates), and global DNA methylation was 22% lower. This is the first time that virtually all features of the methylfolate trap hypothesis have been demonstrated in a human with vitamin B12 deficiency.