bluuebunny/crossref_metadata_2025 huggingface dataset:
Control of Maximum Sarcoplasmic Reticulum Ca Load in Intact Ferret Ventricular Myocytes
Authors: Ginsburg Kenneth S. , Weber Christopher R. , Bers Donald M.
Published: July 2002

In steady state, the Ca content of the sarcoplasmic reticulum (SR) of cardiac myocytes is determined by a balance among influx and efflux pathways. The SR Ca content may be limited mainly by the ATP-supplied chemical potential that is inherent in the gradient between SR and cytosol. That is, forward Ca pumping from cytosol to SR may be opposed by energetically conservative reverse pumping dependent on intra-SR free [Ca]. On the other hand, SR Ca loading may be limited by dissipative pathways (pump slippage and/or pump-independent leak). To assess how SR Ca content is limited, we loaded voltage-clamped ferret ventricular myocytes cumulatively with known amounts of Ca via L-type Ca channels (ICa), using Na-free solutions to prevent Na/Ca exchange. We then measured the maximal resulting caffeine-released SR Ca content under control conditions, as well as when SR Ca pumping was accelerated by isoproterenol (1 μM) or slowed by thapsigargin (0.2–0.4 μM). Under control conditions, SR Ca content reached a limit of 137 μmol·liter cytosol−1 (nonmitochondrial volume) when measured by integrating caffeine-induced Na/Ca exchange currents (∫INaCaXdt) and of 119 μmol·liter cytosol−1 when measured using fluorescence signals dependent on changes in cytosolic free Ca ([Ca]i). When Ca-ATPase pumping rate was slowed 39% by thapsigargin, the maximal SR Ca content decreased by 5 (∫INaCaXdt method) or 23% (fluorescence method); when pumping rate was increased 74% by isoproterenol, SR Ca content increased by 10% (fluorescence method) or 20% (∫INaCaXdt method). The relative stability of the SR Ca load suggests that dissipative losses have only a minor influence in setting the SR Ca content. Indeed, it appears that the SR Ca pump in intact cells can generate a [Ca] gradient approaching the thermodynamic limit.
A new publishing paradigm: STM articles as part of the semantic web
Authors: Rzepa Henry S. , Murray‐Rust Peter
Published: July 2002

An argument is presented for replacing the traditional published scientific technical or medical article, where heavy reliance is placed on human perception of a printed or a printable medium, by a more data‐centric model with well‐defined structures expressed using XML languages. Such articles can be regarded as self‐defining or ‘intelligent’: they can be scaled down to fine‐level details such as, for example, atoms in molecules, up into journals or higher‐order collections, and can be used by software agents as well as humans. Our vision is that this higher‐order concept, often referred to as the semantic web, would lay the foundation for the creation of an open and global knowledge base.
On a high order numerical method for functions with singularities
Authors: Eckhoff Knut
Published: July 2002

By splitting a given singular function into a relatively smooth part and a specially structured singular part, it is shown how the traditional Fourier method can be modified to give numerical methods of high order for calculating derivatives and integrals. Singular functions with various types of singularities of importance in applications are considered. Relations between the discrete and the continuous Fourier series for the singular functions are established. Of particular interest are piecewise smooth functions, for which various important applications are indicated, and for which numerous numerical results are presented.
Convergence analysis of a covolume scheme for Maxwell’s equations in three dimensions
Authors: Nicolaides R. , Wang D.-Q.
Published: July 2002

This paper contains error estimates for covolume discretizations of Maxwell’s equations in three space dimensions. Several estimates are proved. First, an estimate for a semi-discrete scheme is given. Second, the estimate is extended to cover the classical interlaced time marching technique. Third, some of our unstructured mesh results are specialized to rectangular meshes, both uniform and nonuniform. By means of some additional analysis it is shown that the spatial convergence rate is one order higher than for the unstructured case.
Convergence of nonconforming multigrid methods without full elliptic regularity
Authors: Brenner Susanne
Published: July 2002

We consider nonconforming multigrid methods for symmetric positive definite second and fourth order elliptic boundary value problems which do not have full elliptic regularity. We prove that there is a bound (

>
1

>1

) for the contraction number of the

W
W

-cycle algorithm which is independent of mesh level, provided that the number of smoothing steps is sufficiently large. We also show that the symmetric variable

V
V

-cycle algorithm is an optimal preconditioner.
Variations on conservation laws for the wave equation
Authors: Morawetz Cathleen
Published: July 2002

The first part of this paper, presented as an Emmy Noether lecture in connection with the ICM in Berlin in August 1998, gives some examples of using Noether’s theorem for conservation laws for Tricomi-like equations and for the wave equation. It is also shown that equations which are semilinear variations of the wave equation can very often be handled similarly. The type of estimate obtained can even be used to get otherwise unobtainable local estimates for regularity. The fourth part is an introduction to the relation of black holes to the wave equation mainly showing the results of D. Christodoulou. His results use much more difficult estimates not corresponding at all to those in the first part of the paper.
Rotation estimates and spirals
Authors: Gutlyanskiǐ Vladimir , Martio Olli
Published: July 2002

It is shown that the logarithmic spiral gives the extremum to F. John’s angle distortion problem for plane bilipschitz mappings. The problem of factoring spiral-like mappings into a composition of homeomorphisms with smaller isometric distortion is studied. A space counterpart of the Freedman and He theorem is obtained.
Comparative accuracy of methods for protein sequence similarity search.
Authors: Agarwal P , States D J
Published: July 2002

MOTIVATION: Searching a protein sequence database for homologs is a powerful tool for discovering the structure and function of a sequence. Two new methods for searching sequence databases have recently been described: Probabilistic Smith-Waterman (PSW), which is based on Hidden Markov models for a single sequence using a standard scoring matrix, and a new version of BLAST (WU-BLAST2), which uses Sum statistics for gapped alignments. RESULTS: This paper compares and contrasts the effectiveness of these methods with three older methods (Smith-Waterman: SSEARCH, FASTA and BLASTP). The analysis indicates that the new methods are useful, and often offer improved accuracy. These tools are compared using a curated (by Bill Pearson) version of the annotated portion of PIR 39. Three different statistical criteria are utilized: equivalence number, minimum errors and the receiver operating characteristic. For complete-length protein query sequences from large families, PSW's accuracy is superior to that of the other methods, but its accuracy is poor when used with partial-length query sequences. False negatives are twice as common as false positives irrespective of the search methods if a family-specific threshold score that minimizes the total number of errors (i.e. the most favorable threshold score possible) is used. Thus, sensitivity, not selectivity, is the major problem. Among the analyzed methods using default parameters, the best accuracy was obtained from SSEARCH and PSW for complete-length proteins, and the two BLAST programs, plus SSEARCH, for partial-length proteins.
Automated protein sequence database classification. I. Integration of compositional similarity search, local similarity search, and multiple sequence alignment.
Authors: Gracy J , Argos P
Published: July 2002

MOTIVATION: Genome sequencing projects require the periodic application of analysis tools that can classify and multiply align related protein sequence domains. Full automation of this task requires an efficient integration of similarity and alignment techniques. RESULTS: We have developed a fully automated process that classifies entire protein sequence databases, resulting in alignment of the homologous sequences. The successive steps of the procedure are based on compositional and local sequence similarity searches followed by multiple sequence alignments. Global similarities are detected from the pairwise comparison of amino acid and dipeptide compositions of each protein. After the elimination of all but one sequence from each detected cluster of closely related proteins, the remaining sequences are compiled in a suffix tree which is self-compared to detect local sequence similarities. Sets of proteins which share similar sequence segments are then weighted according to their closeness and multiply aligned using a fast hierarchical dynamic programming algorithm. Computational strategies were devised to minimize computer processing time and memory space requirements. The accuracy of the sequence classifications has been evaluated for 12 462 primary structures distributed over 341 known families. The percentage of sequences with missed or incorrect family assignments was 6.8% on the test set. This low error level is only twice that of the manually constructed PROSITE database ( 3.4% ) and is substantially better than that found for the automatically built PRODOM database ( 34.9% ). AVAILABILITY: The resulting database, called DOMO, is available through database search routine SRS at Infobiogen (http://www.infobiogen.fr/srs5/), EBI (http://srs.ebi.ac.uk:5000/) and EMBL (http://www.embl-heidelberg.de/srs5/) World Wide Web sites. CONTACT: gracy@infobiogen.fr
Automatic extraction of motifs represented in the hidden Markov model from a number of DNA sequences.
Authors: Yada T , Totoki Y , Ishikawa M , Asai K , Nakai K
Published: July 2002

MOTIVATION: Automatic extraction of motifs that occur frequently on a set of unaligned DNA sequences is useful for predicting the binding sites of unknown transcription factors. Several programs for this purpose have been released. However, in our opinion, they are not practical enough to be applied to a large number of upstream sequences. RESULTS: We propose a new program called YEBIS (Yet another Environment for the analysis of BIopolymer Sequences) which is capable of extracting a set of motifs, without any a priori knowledge, from a number of functionally related DNA sequences. Using the hidden Markov model, these motifs are represented in a more general form than other conventional methods, such as the weight matrix method. When applied to several sets of benchmark data, it was found that YEBIS had comparable capability to the existing methods, but was much faster. Moreover, it could extract all known motifs from the LTR sequences (long terminal repeat sequences) in a single run. Finally, it could be successfully applied to approximately 400 human promoter sequences and some of the extracted motifs turned out to be known cis-elements. Therefore, YEBIS could be a practical tool for exploring the upstream sequences of genomic ORFs, some of which are regulated in a similar fashion. AVAILABILITY: YEBIS will be distributed to academic users free of charge. All requests should be sent to the address below. CONTACT: E-MAIL: yada@tokyo.jst.go.jp
Gene recognition by combination of several gene-finding programs.
Authors: Murakami K , Takagi T
Published: July 2002

MOTIVATION: A number of programs have been developed to predict the eukaryotic gene structures in DNA sequences. However, gene finding is still a challenging problem. RESULTS: We have explored the effectiveness when the results of several gene-finding programs were re-analyzed and combined. We studied several methods with four programs (FEXH, GeneParser3, GEN-SCAN and GRAIL2). By HIGHEST-policy combination method or BOUNDARY method, approximate correlation (AC) improved by 3-5% in comparison with the best single gene-finding program. From another viewpoint, OR-based combination of the four programs is the most reliable to know whether a candidate exon overlaps with the real exon or not, although it is less sensitive than GENSCAN for exon-intron boundaries. Our methods can easily be extended to combine other programs. AVAILABILITY: We have developed a server program (Shirokane System) and a client program (GeneScope) to use the methods. GeneScope is available through a WWW site (http://gf.genome.ad.jp/). CONTACT: (katsu,takagi)@ims.u-tokyo.ac.jp
WebPHYLIP: a web interface to PHYLIP
Authors: Lim Allison , Zhang Louxin
Published: July 2002

Summary: A web interface to PHYLIP (version 3.57 C) is implemented using CGI/Perl programming. It enables users to do phylogenetic analysis through the Internet.

Availability: WebPHYLIP is available at http://sdmc.krdl.org.sg:8080/~lxzhang/phylip.

Contact: lxzhang@krdl.org.sg
Modeling and predicting transcriptional units of
Escherichia coligenes using hidden Markov models
Authors: Yada Tetsushi , Nakao Mitsuteru , Totoki Yasushi , Nakai Kenta
Published: July 2002

Motivation: The hidden Markov model (HMM) is a valuable technique for gene-finding, especially because its flexibility enables the inclusion of various sequence features. Recent programs for bacterial gene-finding include the information of ribosomal binding site (RBS) to improve the recognition accuracy of the start codon, using this feature. We report here our attempt to extend the model into the total transcriptional unit, enabling the prediction of operon structures.

Results: First, we improved the prediction accuracy of coding sequences (CDSs) by employing the models of ‘typical’, ‘atypical’ and ‘negative (false-positive)’ classes as well as the models of RBS and its downstream spacer. The sensitivity of exactly predicting the 204 experimentally confirmed CDSs reached 90.2% in an objective test. Based on the prediction result of CDSs, the positions of the promoters and terminators were predicted. Our model could exactly recognize 60% of 390 known transcriptional units. Thus, the accuracy and significance of this prediction problem is far from trivial. We would like to propose this problem as an open theme in bioinformatics because the ongoing or planned post-sequencing projects will produce much data for future improvements.

Availability: The table of predicted transcriptional units of Escherichia coli will be distributed upon request.

Contact: knakai@ims.u-tokyo.ac.jp
A novel method for automatic functional annotation of proteins.
Authors: Fleischmann W , M√∂ller S , Gateau A , Apweiler R
Published: July 2002

MOTIVATION: To cope with the increasing amount of sequence data, reliable automatic annotation tools are required. The TrEMBL database contains together with SWISS-PROT nearly all publicly available protein sequences, but in contrast to SWISS-PROT only limited functional annotation. To improve this situation, we had to develop a method of automatic annotation that produces highly reliable functional prediction using the language and the syntax of SWISS-PROT. RESULTS: An algorithm was developed and successfully used for the automatic annotation of a testset of unknown proteins. The predicted information included description, function, catalytic activity, cofactors, pathway, subcellular location, quaternary structure, similarity to other protein, active sites, and keywords. The algorithm showed a low coverage (10%), but a high specificity and reliability. AVAILABILITY: The results can be obtained by anonymous ftp from ftp.ebi.ac.uk/pub/databases/sp_tr_nrdb. The source code is available on request from the authors.
MAD: a suite of tools for microarray data management and
processing
Authors: Liao Birong , Hale Walker , Epstein Charles B. , Butow Ronald A. , Garner Harold R.
Published: July 2002

Summary: Microarray data management and processing (MAD) is a set of Windows integrated software for microarray analysis. It consists of a relational database for data storage with many user-interfaces for data manipulation, several text file parsers and Microsoft Excel macros for automation of data processing, and a generator to produce text files that are ready for cluster analysis.

Availability: Executable is available free of charge on http://pompous.swmed.edu. The source code is also available upon request.

Contact: garner@swmed.edu
Circles: automating the comparative analysis of RNA secondary

structure
Authors: Page Roderic D.M.
Published: July 2002

Summary: Circles is a program for inferring RNA secondary structure using maximum weight matching. The program can read in an alignment in FASTA, ClustalW, or NEXUS format, compute a maximum weight matching, and export one or more secondary structures in various file formats.

Availability: The program is available at no cost from http://taxonomy.zoology.gla.ac.uk/rod/circles/ and requires Windows 95/98/NT.

Contact: r.page@bio.gla.ac.uk
model.it : building three dimensional DNA models from
sequence data
Authors: Vlahovic̆ek Kristian , Pongor Sándor
Published: July 2002

Summary: A WWW server is described for creating 3D models of canonical or bent DNA starting from sequence data. Predicted DNA trajectory is first computed based on a choice of di- and tri-nucleotide models (M.G.Munteanu et al. , Trends Biochem. Sci.23, 341–347, 1998); an atomic model is then constructed and optionally energy-minimized with constrained molecular dynamics. The data are presented as a standard PDB file, directly viewable on the user’s PC using any molecule manipulation program.

Availability: The model.it server is freely available at http://www.icgeb.trieste.it/dna/

Contact: kristian@icgeb.trieste.it; pongor@icgeb.trieste.it

Supplementary information: A series of help files is available at the above address.
Short interrupted palindromes on the extragenic DNA of

Escherichia coli K-12, Haemophilus influenzae and

Neisseria meningitidis
Authors: Vasconcelos Ana T. , Maia Marco A. Grivet Mattoso , de Almeida Darcy F.
Published: July 2002

Motivation: The importance of the various kinds of repetitive nucleotide sequences for the workings of bacterial DNA has been widely recognized. This work is concerned with the distribution of a particular group of repetitive sequences, the short-sequenced interrupted extragenic palindromes, on the genetic maps of Escherichia coli K-12, Haemophilus influenzae Rd and Neisseria meningitidis Z2491 and MC58. A tool has been developed based upon a statistical hypothesis test taking into account the markovian structure of random sequences in order to determine the non-random character of extragenic palindromes.

Results: Totals of 7631, 12904, 4722 and 5477 non-random short interrupted palindromes have been found on the E.coli, H.influenzae, and N.meningitidis serogroup A and serogroup B genomes, respectively. Their distribution patterns on the respective genomes vary according to the bacterial species considered. Based on their position on the genome, palindromes could be distinguished as those which integrate longer, repetitive sequences; those which stand in isolation, and still others are associated to specific genome sites.

Availability: The complete list of the observed palindromes is available at the site http://www/lncc.br/~atrv.

Contact: atrv@lncc.br

**** To whom correspondence should be addressed at Laboratório Nacional de Computação Cientı́fica, Rua Getúlio Vargas 333, Quitandinha, Petrópolis.
IE-Kb: intron exon knowledge base
Authors: Sakharkar Meena K. , Kangueane Pandjassarame , Woon Tong W. , Tan Tin W. , Kolatkar Prasanna R. , Long Manyuan , de Souza Sandro J
Published: July 2002

Summary: IE-Kb (Intron Exon-Knowledge base) illustrates the intron–exon dynamics in eukaryotic genes. We have developed three different knowledge sets, namely ‘Non-redundant ExInt’, ‘Non-redundant Pfam-ExInt complement’ and ‘Non-redundant GenBank eukaryotic subdivisional sets’ to understand this phenomenon. Statistical analysis is performed on each knowledge set and the results are made available online. The entries in knowledge sets are ranked based on their intron length, exon length and protein length with relational hyper-links to the corresponding intron phase, intron position, intron sequence, gene definition and parent GenBank entry.

Availability: http://intron.bic.nus.edu.sg/iekb/iekb.html

Contact: meena@bic.nus.edu.sg

* To whom correspondence should be addressed.
PANAL: an integrated resource for Protein sequence ANALysis
Authors: Silverstein Kevin A. T. , Kilian Alan , Freeman John L. , Johnson James E. , Awad Ihab A. , Retzel Ernest F.
Published: July 2002

Summary: We present PANAL, an integrated resource for protein sequence analysis. The tool allows the user to simultaneously search a protein sequence for motifs from several databases, and to view the result as an intuitive graphical summary.

Availability: PANAL can be freely accessed on our World Wide Web server: http://mgd.ahc.umn.edu/panal/. Source code is available upon request to non-profit organizations.

Contact: panal@ahc.umn.edu

* Authors to whom correspondence should be addressed.
ComboScreen facilitates the multiplex hybridization-based

screening of high-density clone arrays
Authors: Jamison D. Curtis , Thomas James W. , Green Eric D.
Published: July 2002

Motivation: The construction of physical maps based on bacterial clones [e.g. bacterial artificial chromosomes (BACs)] is valuable for a number of molecular genetics applications, including the high-resolution mapping of genomic regions of interest and the identification of clones suitable for systematic sequencing. A common approach for large-scale screening of bacterial clone libraries involves the hybridization of high-density arrays of immobilized, lysed colonies with collections of DNA probes. The use of a multiplex hybridization screening strategy, whereby pooled probes are analysed en masse, simplifies the effort by reducing the total number of parallel experiments required. However, this approach generates large amounts of hybridization-based data that must be carefully analysed, assimilated, and disambiguated in a careful but efficient manner.

Results: To facilitate the screening of high-density clone arrays by a multiplex hybridization approach, we have written a program called ComboScreen. This program provides an organizational framework and analytical tools required for the high-throughput hybridization screening of clone arrays with pools of probes. We have used this program extensively for constructing mouse sequence-ready BAC contig maps.

Availability: ComboScreen is freely available at http://genome.nhgri.nih.gov/comboscreen

Contact: cjamison@informaxinc.com, egreen@nhgri.nih.gov

To whom correspondence should be addressed.
Automatic analysis of agarose gel images
Authors: Umesh Adiga P. S. , Bhomra A. , Turri M. G. , Nicod A. , Datta S. R. , Jeavons P. , Mott R. , Flint J.
Published: July 2002

Motivation: Automatic tools to speed up routine biological processes are very much sought after in bio-medical research. Much repetitive work in molecular biology, such as allele calling in genetic analysis, can be made semi-automatic or task specific automatic by using existing techniques from computer science and signal processing. Computerized analysis is reproducible and avoids various forms of human error. Semi-automatic techniques with an interactive check on the results speed up the analysis and reduce the error.

Results: We have successfully implemented an image processing software package to automatically analyze agarose gel images of polymorphic DNA markers. We have obtained up to 90% accuracy for the classification of alleles in good quality images and up to 70% accuracy in average quality images. These results are obtained within a few seconds. Even after subsequent interactive checking to increase the accuracy of allele classification to 100%, the overall speed with which the data can be processed is greatly increased, compared to manual allele classification.

Availability: The IDL source code of the software is available on request from jonathan.flint@well.ox.ac.uk

* To whom all correspondence should be addressed.
Minimum conflict: a divide-and-conquer approach to phylogeny
estimation
Authors: Fuellen Georg , Wägele Johann-Wolfgang , Giegerich Robert
Published: July 2002

Motivation: Fast and reliable phylogeny estimation is rapidly gaining importance as more and more genomic sequence information is becoming available, and the study of the evolution of genes and genomes accelerates our understanding in biology and medicine alike. Branch attraction phenomena due to unequal amounts of evolutionary change in different parts of the phylogeny are one major problem for current methods, placing the species that evolved fast in one part of the phylogenetic tree, and the species that evolved slowly in the other.

Results: We describe a way to avoid the artifactual attraction of species that evolved slowly, by detecting shared old character states using a calibrated comparison with an outgroup. The corresponding focus on shared novel character states yields a fast and transparent phylogeny estimation algorithm, by application of the divide-and-conquer principle, and heuristic search: shared novelties give evidence of the exclusive common heritage (monophyly) of a subset of the species. They indicate conflict in a split of all species considered, if the split tears them apart. Only the split at the root of the phylogenetic tree cannot have such conflict. Therefore, we can work top-down, from the root to the leaves, by heuristically searching for a minimum-conflict split, and tackling the resulting two subsets in the same way. The algorithm, called ‘minimum conflict phylogeny estimation’ (mcope), has been validated successfully using both natural and artificial data. In particular, we reanalyze published trees, yielding more plausible phylogenies, and we analyze small ‘undisputed’ trees on the basis of alignments considering structural homology.

Availability: mcopeis available via http://bibiserv.techfak.uni-bielefeld.de/mcope/.

Contact: fuellen@alum.mit.edu

* To whom correspondence should be addressed.
SPiD: a subtilis protein interaction database
Authors: Hoebeke Mark , Chiapello Hélène , Noirot Philippe , Bessières Philippe
Published: July 2002

Motivation: Protein–protein interactions are a potential source of valuable clues in determining the functional role of as yet uncharacterized gene products in metabolic pathways. Graph-like structures emerging from the accumulation of interaction data make it difficult to maintain a consistent and global overview by hand. Bioinformatics tools are needed to perform this graph visualization while maintaining a link to the experimental data.

Results: ‘SPiD’ is an online database for exploring networks of interacting proteins in Bacillus subtilis characterized by the two-hybrid system. Graphical displays of interaction networks are created dynamically as users interactively navigate through these networks. Third party applications can interface the database through a Common Object Request Broker Architecture (CORBA) tier.

Availability: SPiD is available through its web site at http://www-mig.versailles.inra.fr/bdsi/SPiD, and through an Interoperable Object Reference (IOR) and its associated Interface Definition Language (IDL).

Contact: hoebeke@versailles.inra.fr

* To whom correspondence should be addressed.
mmsearch: a motif arrangement language and search
program
Authors: Junier Thomas , Pagni Marco , Bucher Philipp
Published: July 2002

Summary: This paper presents a language for describing arrangements of motifs in biological sequences, and a program that uses the language to find the arrangements in motif match databases. The program does not by itself search for the constituent motifs, and is thus independent of how they are detected, which allows it to use motif match data of various origins.

Availability: The program can be tested online at http://hits.isb-sib.ch and the distribution is available from ftp://ftp.isrec.isb-sib.ch/pub/software/unix/mmsearch-1.0.tar.gz

Contact: Thomas.Junier@isrec.unil.ch

Supplementary information: The full documentation about mmsearchis available from http://hits.isb-sib.ch/~tjunier/mmsearch/doc.
Basic Gene Grammars and DNA-ChartParser for language processing

of Escherichia coli promoter DNA sequences
Authors: Leung Siu-wai , Mellish Chris , Robertson Dave
Published: July 2002

Motivation: The field of ‘DNA linguistics’ has emerged from pioneering work in computational linguistics and molecular biology. Most formal grammars in this field are expressed using Definite Clause Grammars but these have computational limitations which must be overcome. The present study provides a new DNA parsing system, comprising a logic grammar formalism called Basic Gene Grammars and a bidirectional chart parser DNA-ChartParser.

Results: The use of Basic Gene Grammars is demonstrated in representing many formulations of the knowledge of Escherichia coli promoters, including knowledge acquired from human experts, consensus sequences, statistics (weight matrices), symbolic learning, and neural network learning. The DNA-ChartParser provides bidirectional parsing facilities for BGGs in handling overlapping categories, gap categories, approximate pattern matching, and constraints. Basic Gene Grammars and the DNA-ChartParser allowed different sources of knowledge for recognizing E.coli promoters to be combined to achieve better accuracy as assessed by parsing these DNA sequences in real-world data sets.

Availability: DNA-ChartParser runs under SICStus Prolog. It and a few examples of Basic Gene Grammars are available at the URL: http://www.dai.ed.ac.uk/~siu/DNA

Contact: {siu,chrism,dr}@dai.ed.ac.uk
Semi-automated update and cleanup of structural RNA alignment

databases
Authors: Gorodkin J. , Zwieb C. , Knudsen B.
Published: July 2002

Summary: We have developed a series of programs which assist in maintenance of structural RNA databases. A main program BLASTs the RNA database against GenBank and automatically extends and realigns the sequences to include the entire range of the RNA query sequences. After manual update of the database, other programs can examine base pair consistency and phylogenetic support. The output can be applied iteratively to refine the structural alignment of the RNA database. Using these tools, the number of potential misannotations per sequence was reduced from 20 to 3 in the Signal Recognition Particle RNA database.

Availability: A quick-server and programs are available at http://www.bioinf.au.dk/rnadbtool/

Contact: gorodkin@bioinf.au.dk

* These authors contributed equally to this work.

† To whom correspondence should be addressed.
Integrated gene and species phylogenies from unaligned whole
genome protein sequences
Authors: Stuart Gary W. , Moffett Karen , Baker Steve
Published: July 2002

Motivation: Most molecular phylogenies are based on sequence alignments. Consequently, they fail to account for modes of sequence evolution that involve frequent insertions or deletions. Here we present a method for generating accurate gene and species phylogenies from whole genome sequence that makes use of short character string matches not placed within explicit alignments. In this work, the singular value decomposition of a sparse tetrapeptide frequency matrix is used to represent the proteins of organisms uniquely and precisely as vectors in a high-dimensional space. Vectors of this kind can be used to calculate pairwise distance values based on the angle separating the vectors, and the resulting distance values can be used to generate phylogenetic trees. Protein trees so derived can be examined directly for homologous sequences. Alternatively, vectors defining each of the proteins within an organism can be summed to provide a vector representation of the organism, which is then used to generate species trees.

Results: Using a large mitochondrial genome dataset, we have produced species trees that are largely in agreement with previously published trees based on the analysis of identical datasets using different methods. These trees also agree well with currently accepted phylogenetic theory. In principle, our method could be used to compare much larger bacterial or nuclear genomes in full molecular detail, ultimately allowing accurate gene and species relationships to be derived from a comprehensive comparison of complete genomes. In contrast to phylogenetic methods based on alignments, sequences that evolve by relative insertion or deletion would tend to remain recognizably similar.

Availability: Both the program used to convert properly formatted sequence files into sparse n-gram matrices (aacode3) and the program used to generate PHYLIP compatible pairwise distance matrices from the Singular Value Decomposition (SVD) output (cosdist) are available at http://mama.indstate.edu/user/stuart. The SVD package is available at http://www.netlib.org/svdpack/index.html, and the PHYLIP package is available at http://evolution.genetics.washington.edu/phylip.html.

Contact: G-Stuart@indstate.edu

* To whom correspondence should be addressed.
A Bayesian approach to discriminate between alternative DNA
sequence segmentations
Authors: Husmeier Dirk , Wright Frank
Published: July 2002

Motivation: As a result of recombination or rate variation, a DNA sequence alignment may have a mosaic structure, where different segments correspond to different evolutionary histories. While several methods have been developed to predict DNA mosaic structures, they do not properly address the question of whether the predicted segmentation itself is statistically significant, or whether it is significantly better than an alternative mosaic structure predicted with another method. The objective of the present article is to devise an approximate Bayesian hypothesis test to discriminate between alternative candidate mosaic structures.

Results: We have applied the proposed discrimination scheme to various synthetic and real-world DNA sequence alignments. On the synthetic data, the algorithm identified the true mosaic structure in nine out of ten cases. On the real-world sequence alignments, it selected the same mosaic structures as predicted in the literature.

Availability: Software written in MATLAB as well as the data sets used in our study are available from http://www.bioss.sari.ac.uk/~dirk/software/ABBESS/INFO.html.

Contact: dirk@bioss.ac.uk; frank@bioss.ac.uk
Tclass: tumor classification system based on gene expression
profile
Authors: Wuju Li , Momiao Xiong
Published: July 2002

Summary: A method that incorporates feature selection into Fisher’s linear discriminant analysis for gene expression based tumor classification and a corresponding program Tclass were developed. The proposed method was applied to a public gene expression data set for colon cancer that consists of 22 normal and 40 tumor colon tissue samples to evaluate its performance for classification. Preliminary results demonstrated that using only a subset of genes ranging from 3 to 10 can achieve high classification accuracy.

Availability: The program is written in Matlab and is being rewritten in the Java language. The source code is available upon request.

Contact: wujuli@china.com; mxiong@sph.uth.tmc.edu.
CGO: utilizing and integrating gene expression microarray data
in clinical research and data management
Authors: Bumm Klaus , Zheng Mingzhong , Bailey Clyde , Zhan Fenghuang , Chiriva-Internati M. , Eddlemon Paul , Terry Julian , Barlogie Bart , Shaughnessy, Jr John D.
Published: July 2002

Summary: Clinical GeneOrganizer (CGO) is a novel windows-based archiving, organization and data mining software for the integration of gene expression profiling in clinical medicine. The program implements various user-friendly tools and extracts data for further statistical analysis. This software was written for Affymetrix GeneChip©*.txt files, but can also be used for any other microarray-derived data. The MS-SQL server version acts as a data mart and links microarray data with clinical parameters of any other existing database and therefore represents a valuable tool for combining gene expression analysis and clinical disease characteristics.

Availability: The software is available free of charge at http://lambertlab.uams.edu

Contact: ShaughnessyJohn@uams.edu

Supplementary information: A snapshot of detailed program-specific table relationships and information on other programs including various cancer gene expression profiles are available on above mentioned web site.

* To whom correspondence should be addressed.
Assessing the significance of consistently mis-regulated genes
in cancer associated gene expression matrices
Authors: Wahde Mattias , Klus Gregory T. , Bittner Michael L. , Chen Yidong , Szallasi Zoltan
Published: July 2002

Motivation: The simplest level of statistical analysis of cancer associated gene expression matrices is aimed at finding consistently up- or down-regulated genes within a given set of tumor samples. Considering the high level of gene expression diversity detected in cancer, one needs to assess the probability that the consistent mis-regulation of a given gene is due to chance. Furthermore, it is important to determine the required sample number that will ensure the meaningful statistical analysis of massively parallel gene expression measurements.

Results: The probability of consistent mis-regulation is calculated in this paper for binarized gene expression data, using combinatorial considerations. For practical purposes, we also provide a set of accurate approximate formulas for determining the same probability in a computationally less intensive way. When the pool of mis-regulatable genes is restricted, the probability of consistent mis-regulation can be overestimated. We show, however, that this effect has little practical consequences for cancer associated gene expression measurements published in the literature. Finally, in order to aid experimental design, we have provided estimates on the required sample number that will ensure that the detected consistent mis-regulation is not due to chance. Our results suggest that less than 20 sufficiently diverse tumor samples may be enough to identify consistently mis-regulated genes in a statistically significant manner.

Availability: An implementation using Mathematica tm of the main equation of the paper, (4), is available at www.me.chalmers.se/~mwahde/bioinfo.html.

Contact: mwahde@me.chalmers.se, zszallasi@chip.org

* To whom correspondence should be addressed.
CASA: a server for the critical assessment of protein sequence
alignment accuracy
Authors: Kahsay Robel Y. , Wang Guoli , Dongre Nataraj , Gao Guang , Dunbrack, Jr Roland L.
Published: July 2002

Summary: A public server for evaluating the accuracy of protein sequence alignment methods is presented. CASA is an implementation of the alignment accuracy benchmark presented by Sauder et al. (Proteins, 40, 6–22, 2000). The benchmark currently contains 39321 pairwise protein structure alignments produced with the CE program from SCOP domain definitions. The server produces graphical and tabular comparisons of the accuracy of a user’s input sequence alignments with other commonly used programs, such as BLAST, PSI-BLAST, Clustal W, and SAM-T99.

Availability: The server is located at http://capb.dbi.udel.edu/casa.

Contact: RL_ Dunbrack@fccc.edu

* To whom correspondence should be addressed.
Desktop prediction/analysis of mass spectrometric data in
proteomic projects by using massXpert
Authors: Rusconi Filippo , Belghazi Maya
Published: July 2002

Summary: With the ever-increasing demand for biopolymer mass spectrometry, specialized software is needed to both predict and process mass spectrometric data. With massXpert, we present a proteomics-oriented program mainly concerned with protein physico-chemistry and protein/peptide mass spectra simulations.

Availability: The massXpert program is free for academic and commercial use at http://frl.lptc.u-bordeaux.fr.

Contact: frusconi@lptc.u-bordeaux.fr

Supplementary information: The http://frl.lptc.u-bordeaux.frsite contains a tutorial for online perusal or download.

2 To whom correspondence should be addressed at: LPTC UMR CNRS 5472, UniversitéBordeaux I, F-33405 Talence Cedex, France.
Efficient membrane assembly of the KcsA potassium channel in Escherichia coli requires the protonmotive force
Authors: van Dalen Annemieke , Schrempf Hildgund , Killian J Antoinette , de Kruijff Ben
Published: July 2002

Very little is known about the biogenesis and assembly of oligomeric membrane proteins. In this study, the biogenesis of KcsA, a prokaryotic homotetrameric potassium channel, is investigated. Using in vivo pulse–chase experiments, both the monomeric and tetrameric form could be identified. The conversion of monomers into a tetramer is found to be a highly efficient process that occurs in the Escherichia coli inner membrane. KcsA does not require ATP hydrolysis by SecA for insertion or tetramerization. The presence of the protonmotive force (pmf) is not necessary for transmembrane insertion of KcsA; however, the pmf proved to be essential for the efficiency of oligomerization. From in vivo and in vitro experiments it is concluded that the electrical component, Δψ, is the main determinant for this effect. These results demonstrate a new role of the pmf in membrane protein biogenesis.
Signalling of abscisic acid to regulate plant growth
Authors: Himmelbach Axel , Iten Monika , Grill Erwin
Published: July 2002

Abscisic acid (ABA) mediated growth control is a fundamental response of plants to adverse environmental cues. The linkage between ABA perception and growth control is currently being unravelled by using different experimental approaches such as mutant analysis and microinjection experiments. So far, two protein phosphatases, ABI1 and ABI2, cADPR, pH and Ca
2+
have been identified as main components of the ABA signalling pathway. Here, the ABA signal transduction pathway is compared to signalling cascades from yeast and mammalian cells. A model for a bifurcated ABA signal transduction pathway exerting a positive and negative control mechanism is proposed.
Gene Expression Analysis with Universal n-mer Arrays
Authors: van Dam R. Michael , Quake Stephen R.
Published: July 2002

Gene expression profiling is one of the many applications that have benefited from the massively parallel nucleic acid detection capability of DNA microarrays. Current expression arrays, however, are expensive and inflexible. They are custom-designed for each organism and they do not offer the possibility of incorporating updated genomic information without production of a new chip. One possible solution is the development of a universal chip, consisting of all 4n possible DNA sequences of length n. Studying different organisms or new genes would simply require modifications to the hybridization pattern analysis software. The key problem is to find a value of n that is large enough to afford sufficient specificity, yet is small enough for practical fabrication and readout. We developed an analytical model, supported by computer-assisted calculation with yeast and mouse transcript data, to argue that it is both practical and useful to fabricate n-mer arrays with 10 ⩽ n ⩽ 16.
Half‐scan cone‐beam CT fluoroscopy with multiple x‐ray sources
Authors: Liu Ying , Liu Hong , Wang Ying , Wang Ge
Published: July 2002

To develop volumetric micro‐CT fluoroscopy for small animal imaging, we have proposed a cone‐beam system with multiple x‐ray sources. In this paper, we extend Parker's single‐source half‐scan weighting scheme to the case of an odd number of x‐ray sources that are equiangularly distributed, and apply it for half‐scan Feldkamp‐type reconstruction in this unique geometry. In the numerical simulation with the Shepp–Logan phantom, representative images indicate that the proposed half‐scan Feldkamp‐type algorithm produces temporal resolution significantly superior to that with a single x‐ray source cone‐beam system.
Computer‐aided diagnostic scheme for lung nodule detection in digital chest radiographs by use of a multiple‐template matching technique
Authors: Li Qiang , Katsuragawa Shigehiko , Doi Kunio
Published: July 2002

We have been developing a computer‐aided diagnostic (CAD) scheme to assist radiologists in improving the detection of pulmonary nodules in chest radiographs, because radiologists can miss as many as 30% of pulmonary nodules in routine clinical practice. A key to the successful clinical application of a CAD scheme is to ensure that there are only a small number of false positives that are incorrectly reported as nodules by the scheme. In order to significantly reduce the number of false positives in our CAD scheme, we developed, in this study, a multiple‐template matching technique, in which a test candidate can be identified as a false positive and thus eliminated, if its largest cross‐correlation value with non‐nodule templates is larger than that with nodule templates. We describe the technique for determination of cross‐correlation values for test candidates with nodule templates and non‐nodule templates, the technique for creation of a large number of nodule templates and non‐nodule templates, and the technique for removal of nodulelike non‐nodule templates and non‐nodulelike nodule templates, in order to achieve a good performance. In our study, a large number of false positives (44.3%) were removed with reduction of a very small number of true positives (2.3%) by use of the multiple‐template matching technique. We believe that this technique can be used to significantly improve the performance of CAD schemes for lung nodule detection in chest radiographs.
Inverse radiation treatment planning using the Dynamically Penalized Likelihood method
Authors: Llacer Jorge
Published: July 2002

In this paper we present a new method of solving the inverse radiation treatment planning problem. The method is based on a Maximum Likelihood Estimator with dynamically changing penalization terms. The resulting Dynamically Penalized Likelihood (DPL) algorithm achieves a dose distribution of excellent uniformity in a tumor volume and a much lower dose in regions containing sensitive volumes. A simple model of a patient and of energy deposition has been used for the initial results presented: a two‐dimensional computer generated phantom and monochromatic x rays, without scattering. Three two‐dimensional problems are solved with the DPL algorithm, corresponding to different size and spatial relationships between the tumor and sensitive tissue volumes. The results show that the DPL algorithm is robust and flexible; it only requires moderate computation times and leads to promising solutions, even in rather difficult problems. The results encourage the extension of the present work to more realistic therapy situations.