bluuebunny/crossref_metadata_2025_split huggingface dataset:
A new dynamic Bayesian network (DBN) approach for identifying gene regulatory networks from time course microarray data
Authors: Zou Min , Conzen Suzanne D. 
Published: August 2004

AbstractMotivation: Signaling pathways are dynamic events that take place over a given period of time. In order to identify these pathways, expression data over time are required. Dynamic Bayesian network (DBN) is an important approach for predicting the gene regulatory networks from time course expression data. However, two fundamental problems greatly reduce the effectiveness of current DBN methods. The first problem is the relatively low accuracy of prediction, and the second is the excessive computational time.Results: In this paper, we present a DBN-based approach with increased accuracy and reduced computational time compared with existing DBN methods. Unlike previous methods, our approach limits potential regulators to those genes with either earlier or simultaneous expression changes (up- or down-regulation) in relation to their target genes. This allows us to limit the number of potential regulators and consequently reduce the search space. Furthermore, we use the time difference between the initial change in the expression of a given regulator gene and its potential target gene to estimate the transcriptional time lag between these two genes. This method of time lag estimation increases the accuracy of predicting gene regulatory networks. Our approach is evaluated using time-series expression data measured during the yeast cell cycle. The results demonstrate that this approach can predict regulatory networks with significantly improved accuracy and reduced computational time compared with existing DBN approaches.Availability: The programs described in this paper can be obtained from the corresponding author upon request.Contact: sconzen@medicine.bsd.uchicago.edu
BioLingua: a programmable knowledge environment for biologists
Authors: Massar J. P. , Travers Michael , Elhai Jeff , Shrager Jeff 
Published: August 2004

AbstractSummary: BioLingua is an interactive, web-based programming environment that enables biologists to analyze biological systems by combining knowledge and data through direct end-user programming. BioLingua embeds a mature symbolic programming language in a frame-based knowledge environment, integrating genomic and pathway knowledge about a class of similar organisms. The BioLingua language provides interfaces to numerous state-of-the-art bioinformatic tools, making these available as an integrated package through the novel use of web-based programmability and an integrated Wiki-based community code and data store. The pilot instantiation of BioLingua, which has been developed in collaboration with several cyanobacteriologists, integrates knowledge about a subset of cyanobacteria with the Gene Ontology, KEGG and BioCyc knowledge bases. We introduce the BioLingua concept, architecture and language, and give several examples of its use in complex analyses.Availability: Extensive documentation is available online at http://nostoc.stanford.edu/Docs/index.htmlContact: JShrager@Stanford.edu
Protein structure alignment by deterministic annealing
Authors: Chen Luonan , Zhou Tianshou , Tang Yun 
Published: August 2004

Abstract
Motivation: Protein structure alignment is one of the most important computational problems in molecular biology and plays a key role in protein structure prediction, fold family classification, motif finding, phylogenetic tree reconstruction and so on. From the viewpoint of computational complexity, a pairwise structure alignment is also a NP-hard problem, in contrast to the polynomial time algorithm for a pairwise sequence alignment.
Results: We propose a method for solving the structure alignment problem in an accurate manner at the amino acid level, based on a mean field annealing technique. We define the structure alignment as a mixed integer-programming (MIP) problem. By avoiding complicated combinatorial computation and exploiting the special structure of the continuous partial problem, we transform the MIP into a reduced non-linear continuous optimization problem (NCOP) with a much simpler form. To optimize the reduced NCOP, a mean field annealing procedure is adopted with a modified Potts model, whose solution is generally identical to that of the MIP. There is no ‘soft constraint’ in our mean field model and all constraints are automatically satisfied throughout the annealing process, thereby not only making the optimization more efficient but also eliminating many unnecessary parameters that depend on problems and usually require careful tuning. A number of benchmark examples are tested by the proposed method with comparisons to several existing approaches.
Contact: chen@elec.osaka-sandai.ac.jp
SNP Chart: an integrated platform for visualization and interpretation of microarray genotyping data
Authors: Tebbutt Scott J. , Opushnyev Igor V. , Tripp Ben W. , Kassamali Ayaz M. , Alexander Wendy L. , Andersen Marilyn I. 
Published: August 2004

Abstract
Summary: SNP Chart is a Java application for the visualization and interpretation of microarray genotyping data primarily derived from arrayed primer extension-based chemistries. Spot intensity output files from microarray analysis tools are imported into SNP Chart, together with a multi-channel TIFF image of the original array experiment and a list of the actual single nucleotide polymorphisms (SNPs) being tested. Data from different and/or replicate probes that interrogate the same SNP, but that are scattered across the array grid, can be reassembled into a single chart format, specific for the SNP. This allows a quick and very effective ‘visualization’/‘quality control’ of the data from multiple probes for the same SNP that can be easily interpreted and manually scored as a genotype.
Availability: http://www.snpchart.ca
Contact: stebbutt@mrl.ubc.ca
Supplementary information: A comprehensive manual describing SNP Chart is available at the above website, together with sample data files.
Simulation of specimen‐induced aberrations for objects with spherical and cylindrical symmetry
Authors: SCHWERTNER M. , BOOTH M. J. , WILSON T. 
Published: August 2004

SummaryWavefront aberrations caused by the refractive index structure of the specimen are known to compromise signal intensity and three‐dimensional resolution in confocal and multiphoton microscopy. However, adaptive optics can measure and correct specimen‐induced aberrations. For the design of an adaptive optics system, information on the type and amount of the aberration is required. We have previously described an interferometric set‐up capable of measuring specimen‐induced aberrations and a method for the extraction of the Zernike mode content. In this paper we have modelled specimen‐induced aberrations caused by spherical and cylindrical objects using a ray tracing method. The Zernike mode content of the wavefronts was then extracted from the simulated wavefronts and compared with experimental results. Aberrations for a simple model of an oocyte cell consisting of two spherical regions and for a model of a well‐characterized optical fibre are calculated. This simple model gave Zernike mode data that are in good agreement with experimental results.
Microscopy and microanalysis of crystalline glazes
Authors: KNOWLES K. M. , FREEMAN F. S. H. B. 
Published: August 2004

SummaryCrystalline glazes on ceramic plates produced commercially in the U.K. and on ceramic pots produced commercially in Taiwan and Spain have been examined by X‐ray diffraction, conventional and polarized light microscopy, and scanning electron microscopy in order to identify the crystalline phases present in the glazes and to ascertain through X‐ray microanalysis the partitioning behaviour of the transition metal ions used to colour the glazes and the crystals within them. In each case examined, the macroscopic two‐dimensional spherulites within the glazes clearly seen by the naked eye were found to consist of large numbers of radially orientated acicular crystals each 5 µm or less in width embedded within the silica‐rich glaze. Energy dispersive X‐ray microanalysis and X‐ray diffraction of these crystals identified these crystals as willemite, α‐Zn2SiO4. The strong [001] texture of these crystals within the glaze evident from the X‐ray diffraction patterns was consistent with polarized light microscopy observations of the willemite crystals. In addition to willemite, small iron‐doped gahnite (ZnAl2O4) crystals were found in a honey‐coloured crystalline glaze and acicular rutile (TiO2) crystals were found in the Portmeirion Pottery plates examined. Transition metal ions with a preference for tetrahedral coordination were observed to substitute for Zn2+ ions in willemite and to partition preferentially to the willemite crystals, whereas ions preferring octahedral coordination preferred to remain in the glaze.
Conformational dynamics of single molecules visualized in real time by scanning force microscopy: macromolecular mobility on a substrate surface in different vapours
Authors: GALLYAMOV M. O. , TARTSCH B. , KHOKHLOV A. R. , SHEIKO S. S. , BÖRNER H. G. , MATYJASZEWSKI K. , MÖLLER M. 
Published: August 2004

SummaryWe describe a technique to visualize and effect in real time motion and conformational transitions of single macromolecules. Two steps are involved. First, scanning force microscopy (SFM) was applied to detect in situ conformational transitions of single polymer molecules adsorbed on a substrate surface. Secondly, these changes were induced by controlled variations of environmental conditions in a microscope environmental chamber. In particular, we have revealed that exposure of a substrate with adsorbed macromolecules to vapours of different nature was able to increase molecular mobility and to stimulate conformational transitions of the polymer chains on the surface. Realization of SFM observation in a variable vapour environment was not as difficult as in liquid media. Variations of the vapour composition affected the oscillation dynamics of the cantilever with the scanning probe only to a small extent, and did not impede continuation of the scanning procedure. In fact, the characteristic times of the observed conformational changes were large enough (minutes to dozens of minutes) for sampling images repeatedly. Although recording of an SFM image was slow and required several minutes, we were able to visualize step‐by‐step the successive stages of the slow conformational transformation of the macromolecules adhering to the substrate, i.e. to investigate a molecular response to the environment changes in real time. Here, we studied the reversible collapse–decollapse transitions of cylindrical poly(methacrylate)‐graft‐poly(n‐butyl acrylate) brush‐like macromolecules exposed to different vapours. Single macromolecules on mica tended to assume a compacted globular conformation when exposed to the vapour of compounds, which due to their amphiphilic nature adsorb on mica and lower the surface energy of the substrate (e.g. alcohols). By contrast, the macromolecules adopted extended two‐dimensional worm‐like conformations in the vapours of compounds having high values of surface tension (such as water). In our opinion, the reason for the observed tendency was a competition in spreading on the substrate surface between the macromolecules and the co‐adsorbed vapour molecules. If the brush‐like macromolecules succeeded in the spreading, they acquired an extended conformation. Otherwise they collapsed to globuli in order to reduce the surface area per macromolecule. Thus, the enhanced mobility of synthetic macromolecules on a substrate observed in a vapour environment in combination with the possibility to manipulate the macromolecular conformation via changes in a vapour phase and the ability to visualize the transitions of the macromolecules individually, provides challenging prospects for SFM studies on the dynamics of single molecules under applied external stimuli.
Analytical methods Of assessing the image quality associated with digital and photographic imaging systems
Authors: Thomson Grant H. 
Published: August 2004

AbstractThe introduction of digital cameras for aerial survey photography and use of scanners with processed aerial film present a number of technical questions concerning the way photography is to be acquired in the future. Among the questions to be addressed are the comparative metric properties of images acquired by each system and the associated image quality characteristics. The new digital camera systems will require very careful appraisal, using well‐established methods of assessing metric quality already available to survey organisations. The questions concerning image quality are more difficult to answer, as they require very specialised instrumentation if measurements are to be made directly in practice. Over the course of the past several decades a more analytical approach to assessing image quality has emerged, and one that may be used by individuals. The method is particularly effective where information on the micro‐image characteristics of products is made available by the manufacturers concerned. An outline is given of some considerations that need to be taken into account when using an analytical approach, with references given for further reading.
UNIONS AND EMPLOYMENT GROWTH IN BRITISH WORKPLACES DURING THE 1990S: A PANEL ANALYSIS
Authors: Bryson Alex 
Published: August 2004

AbstractThis paper uses the 1990–1998 Workplace Industrial Relations Survey Panel to analyse the impact of unions on employment growth among private sector workplaces in Britain. The growth rate among unionised workplaces was roughly 3–4% per annum lower than among non‐unionised workplaces, ceteris paribus. The effect is not accounted for by the age of unionised workplaces, union concentration in declining industries, or organisational or technical change at workplace level. The effect remains once we account for the impact of unions on workplace survival. However, effects are only apparent where unions do not negotiate over employment and where unions have some degree of bargaining strength.
INDUSTRIAL POLICY IN GREAT BRITAIN AND ITS EFFECT ON TOTAL FACTOR PRODUCTIVITY IN MANUFACTURING PLANTS, 1990–1998
Authors: Harris Richard , Robinson Catherine 
Published: August 2004

AbstractIndustrial policy in any economy has a number of varying and occasionally conflicting objectives, but the overarching intention of the various grants, subsidies and support schemes, arguably, must be to improve the economic performance of the plants they assist directly. However, in the absence of counterfactual evidence, whether or not assistance does improve performance is hard to establish. In this paper, we consider the impact of two UK government industrial support schemes (Regional Selective Assistance and the Small Firm Merit Awards for Research and Technology) on UK manufacturing plant level total factor productivity in an attempt to answer the question, ‘did assistance make a difference?’
BANKING LICENCES, BAILOUTS AND REGULATOR ABILITY
Authors: Morrison Alan D. 
Published: August 2004

AbstractI analyse a model in which it is socially optimal for banks to manage depositor funds but in which concerns about fraud discourage depositing and justify regulation. The regulator screens bankers and decides the level of charter value which they will receive as incentive to prevent fraud. She can also encourage deposits by insuring them. The optimal policy depends upon the regulator's screening ability: high ability regulators rely upon charter value and low ability regulators rely upon deposit insurance. I relate these findings to the regulation of transition economy banks, to operational risk management, and to banking competition policy.
A minipig model of high‐fat/high‐sucrose diet‐induced diabetes and atherosclerosis
Authors: Xi Shoumin , Yin Weidong , Wang Zongbao , Kusunoki Masataka , Lian Xin , Koike Tomonari , Fan Jianglin , Zhang Qiuju 
Published: August 2004

SummaryType 2 diabetes is a major risk factor of the development of atherosclerosis in humans. However, studies examining mechanisms underlying diabetes‐accelerated atherosclerosis have been limited by the lack of suitable humanoid animal models. Pigs have a cardiovascular system that is very similar to that of humans and is useful as a model for human physiology and pathophysiology. In this study, we established a new miniature pig model for studying dyslipidaemia and atherosclerosis in diabetes. Chinese Guizhou minipigs were fed a normal control diet or a high‐fat/high‐sucrose diet (HFSD) for 6 months. Plasma total cholesterol (TC), high‐density lipoprotein cholesterol, triglyceride (TG), insulin and glucose were quantified at monthly intervals. The induction of insulin resistance and dysfunction of the pancreatic β‐cell were assessed by oral glucose tolerance test and insulin sensitivity test. The aortic fatty streak lesions were quantified following lipid staining with Sudan IV. During the feeding period, mild high plasma TC and TG were induced. At the end of 6 months, in HFSD‐fed animals, the adipocytes were hypertrophic, fat deposit in the liver was observed, loss of pancreatic β‐cells was observed, and the aortic fatty streak lesions were clearly present in the animals' aortas. Our study established that miniature pigs that were fed a HFSD without adding dietary cholesterol developed insulin resistance, mild diabetes and atherosclerotic lesions. HFSD‐fed miniature pigs may be good animal models for research on the treatment of diabetic dyslipidaemia complicated with atherosclerosis.
Changes in mucin‐type O‐glycosylation in breast cancer: implications for the host immune response
Authors: Taylor‐Papadimitriou Joyce , Burchell Joy M. , Miles David , Sewell Robert 
Published: August 2004

The major epithelial mucin, which is expressed by more than 90% of breast carcinomas and epithelial breast cancer cell lines, is MUC1. The MUC1 membrane mucin has a relatively simple structure, where a tandem repeat (TR) region carrying multiple O‐glycans forms the major part of the extracellular domain. The gene shows a size polymorphism, due to variation in the number of tandem repeats, each of which has five potential glycosylation sites. MUC1 has been found to be a good model for studying mucin‐type O‐glycosylation both in vitro and in vivo.Changes in the pattern of glycosylation of MUC1 have been observed in breast cancer (Burchell et al. 2001) and have led to an interest in MUC1 as a possible target antigen for immunotherapeutic intervention (Taylor‐Papadimitriou et al. 2000). The mucin expressed at high levels in the normal lactating mammary gland carries mainly core 2‐based O‐glycans (2–3 per tandem repeat). In breast cancers, the level of the ST3 Gal 1 enzyme is elevated (Burchell et al. 1999) and this is associated with increased numbers of Sialyl T O‐glycans being added, as predicted from in vitro studies, showing competition for the core 1 substrate between this sialyl transferase and the relevant core 2 enzyme (Dalziel et al. 2001). Moreover, the TR domain is more densely glycosylated. While the Sialyl T O‐glycan is commonly found on normal cells (e.g. resting T cells), it is cancer associated in the mammary gland. However, several lines of evidence indicate that this MUC1 glycoform, as expressed on breast cancers, can be immunosuppressive, maybe reflecting an inhibitory interaction with a lectin, possibly a siglec (Nath et al. 1999), on immune effector cells. In 25–30% of breast cancers, O‐glycosylation is terminated very early so that GalNAc (Tn) or NeuAc α2,6 GalNAc (Sialyl Tn) glycans appear. Sialyl Tn is highly tumour‐specific and is detected immunohistochemically only when the enzyme ST6GalNAcI is expressed. The Tn and Sialyl Tn will bind to different lectins, including MGL and could stimulate the immune response. Preliminary studies in mouse models suggest that an immunization protocol which includes MUC1‐carrying Sialyl Tn O‐glycans can protect against tumour growth, while clinical studies in breast cancer patients using immunogens based on the Sialyl Tn glycan are underway.
Molecular recognition and modulation of hepatocyte growth factor activity by heparan and dermatan sulfates
Authors: Catlow Krista , Deakin Jon A. , Delehedde Maryse , Fernig David G. , Pavao Mauro S.G. , Gallagher John T. , Lyon Malcolm 
Published: August 2004

Introduction  Hepatocyte growth factor/scatter factor (HGF/SF) is an unusual growth factor in that it binds both heparan sulfate (HS) (Lyon et al. 1994) and dermatan sulfate (DS) (Lyon et al. 1998) glycosaminoglycans (GAGs) with similar high affinities. Both these GAGs act as co‐receptors for HGF/SF in the activation of the Met receptor (Lyon et al. 2002). Our aim was to determine the sequences in HS and DS that specifically interact with and modulate HGF/SF activity.Materials and methods  A structurally unique DS, which possesses O‐sulfation at carbon‐6 of the hexosamine residue (and not carbon‐4 as in mammalian DS), was obtained from the sea cucumber, Ascidia nigra. A variety of HS‐ and DS‐like structures were also generated using various chemical modification procedures (specific desulfations and carboxyl reductions). The ability of these various GAG species to compete with cell surface GAGs for HGF/SF binding was tested using radiolabelled HGF/SF and MDCK cells. The modified GAG structures and the A. nigra DS are currently being tested for their ability to act as co‐receptors for the interaction between HGF/SF and Met by studying cell signalling and cellular response assays, using the sulfated GAG‐deficient CHO‐745 cell line.Results  Unexpectedly, A. nigra DS was found to bind HGF/SF strongly with a KD of around 1 nm. This interaction is 20‐fold stronger than that of between HGF/SF and mammalian DS, but similar to that of with HS. A. nigra DS also stimulated HGF/SF‐mediated Erk activation and migration in CHO‐745 cells. Studies using the modified GAG species showed that, in the case of HS, 6‐O‐sulfate and N‐sulfate groups are most important for HGF/SF binding. For HGF/SF binding to DS, hexosamine O‐sulfate is most important. HGF/SF was also found to bind 6‐O‐sulfated GAGs more strongly than 4‐O‐sulfated ones.Discussion  The data show that there is flexibility in the structures recognized by HGF/SF, and this explains the ability of the growth factor to bind both HS and DS. However, there are still observable preferences in GAG structure, such as 6‐O‐sulfation over 4‐O‐sulfation. Information on HGF/SF‐binding GAG structures is valuable for the design of HGF/SF antagonists that could be useful therapeutically in the treatment of solid tumours where HGF/SF‐Met activity is up‐regulated.