bluuebunny/crossref_metadata_2025 huggingface dataset:
DIVCLUS: an automatic method in the GEANFAMMER package that finds homologous domains in single- and multi-domain proteins.
Authors: Park J , Teichmann S A
Published: July 2002

MOTIVATION: Large-scale determination of relationships between the proteins produced by genome sequences is now common. All protein sequences are matched and those that have high match scores are clustered into families. In cases where the proteins are built of several domains or duplication modules, this can lead to misleading results. Consider the very simple example of three proteins: 1, formed by duplication modules A and B; 2, formed by duplication modules B' and C; and 3, formed by duplication modules C' and D. Duplication modules B and B' are homologous, as are C and C'. Matching the sequences of 1, 2 and 3 followed by simple single-linkage clustering would put all three in the same family, even though proteins 1 and 3 are not related. This is because the different parts of 2 match 1 and 3. This paper describes a procedure, DIVCLUS, that divides such complex clusters of partially related sequences into simple clusters that contain only related duplication modules. In the example just given, it would produce two groups of sequences: the first with domains B of sequence 1 and B of sequence 2, and the second with domain C of sequence 2 and C of sequence 3. DIVCLUS is part of a package called GEANFAMMER, for GEnome ANalysis and protein FAMily MakER. The package automates the detection of families of duplication modules from a protein sequence database. RESULTS: DIVCLUS has been applied to the division of single-linkage clusters generated from the protein sequences of six completely sequenced bacterial genomes. Out of 12 013 genes in these six genomes, 4563 single- and multi-domain sequences formed 1071 complex clusters. Application of the DIVCLUS program resolved these clusters into 2113 clusters corresponding to single duplication modules. AVAILABILITY: The perl5 program and its documentation are available at the following address: http://www.mrc-lmb.cam.ac.uk/genomes/ and by anonymous ftp at ftp.mrc-lmb.cam.ac.uk in the directory /pub/genomes/Software/. CONTACT: sat@mrc-lmb.cam.ac.uk; jong@mrc-lmb. cam.ac.uk
Statistics of large-scale sequence searching.
Authors: Spang R , Vingron M
Published: July 2002

MOTIVATION: Database search programs such as FASTA, BLAST or a rigorous Smith-Waterman algorithm produce lists of database entries, which are assumed to be related to the query. The computation of statistical significance of similarity scores is well established for single pairs of sequences and using purely random models. However, the multi-trial context of a database search poses new problems. The credibility of a certain score obtained in a database search decreases with the amount of data that is compared. To improve p-value computation for database search experiments, statistical properties of the databases, such as the distribution of sequence length and effects induced by frequently repeated sequence patterns, need to be taken into account. RESULTS: We investigated the SWISS-PROT protein database Release 31.0 running extensive simulations of database searches. A discrepancy is observed between the theoretical predictions and the empirical distribution. To correct for this, we evaluate the statistical significance of scores in the context of a database search by a contrasting semi-random model. This model enhances purely random models by one additional parameter reflecting individual statistical properties of real databases. We call this parameter the effective size of the database. CONTACT: r.spang@dkfz-heidelberg.de;m.vingron@dkfz-hei del berg.de
An RNA folding method capable of identifying pseudoknots and base triples.
Authors: Tabaska J E , Cary R B , Gabow H N , Stormo G D
Published: July 2002

MOTIVATION: Recently, we described a Maximum Weighted Matching (MWM) method for RNA structure prediction. The MWM method is capable of detecting pseudoknots and other tertiary base-pairing interactions in a computationally efficient manner (Cary and Stormo, Proceedings of the Third International Conference on Intelligent Systems for Molecular Biology, pp. 75-80, 1995). Here we report on the results of our efforts to improve the MWM method's predictive accuracy, and show how the method can be extended to detect base interactions formerly inaccessible to automated RNA modeling techniques. RESULTS: Improved performance in MWM structure prediction was achieved in two ways. First, new ways of calculating base pair likelihoods have been developed. These allow experimental data and combined statistical and thermodynamic information to be used by the program. Second, accuracy was improved by developing techniques for filtering out spurious base pairs predicted by the MWM program. We also demonstrate here a means by which the MWM folding method may be used to detect the presence of base triples in RNAs. AVAILABILITY: http://www.cshl.org/mzhanglab/tabaska/j axpage. html CONTACT: tabaska@cshl.org
BAliBASE: a benchmark alignment database for the evaluation of multiple alignment programs.
Authors: Thompson J D , Plewniak F , Poch O
Published: July 2002

SUMMARY: BAliBASE is a database of manually refined multiple sequence alignments categorized by core blocks of conservation sequence length, similarity, and the presence of insertions and N/C-terminal extensions. AVAILABILITY: From http://www-igbmc. u-strasbg.fr/BioInfo/BAliBASE/index.html
USAGE: a web-based approach towards the analysis of SAGE data
Authors: van Kampen A. H. C. , van Schaik B. D. C. , Pauws E. , Michiels E. M. C. , Ruijter J. M. , Caron H. N. , Versteeg R. , Heisterkamp S. H. , Leunissen J. A. M. , Baas F. , van der Mee M.
Published: July 2002

Motivation: SAGE enables the determination of genome-wide mRNA expression profiles. A comprehensive analysis of SAGE data requires software, which integrates (statistical) data analysis methods with a database system. Furthermore, to facilitate data sharing between users, the application should reside on a central server and be accessed via the internet. Since such an application was not available we developed the USAGE package.

Results: USAGE is a web-based application that comprises an integrated set of tools, which offers many functions for analysing and comparing SAGE data. Additionally, USAGE includes a statistical method for the planning of new SAGE experiments. USAGE is available in a multi-user environment giving users the option of sharing data. USAGE is interfaced to a relational database to store data and analysis results. The USAGE query editor allows the composition of queries for searching this database. Several database functions have been included which enable the selection and combination of data. USAGE provides the biologist increased functionality and flexibility for analysing SAGE data.

Availability: USAGE is freely accessible for academic institutions at http://www.cmbi.kun.nl/usage/. The source code of USAGE is freely available for academic institutions on request from the first author.

Contact: a.h.vankampen@amc.uva.nl

To whom correspondence should be addressed.
Finding pathogenicity islands and gene transfer events in
genome data
Authors: Liò Pietro , Vannucci Marina
Published: July 2002

Motivation: There is a growing literature on wavelet theory and wavelet methods showing improvements on more classical techniques, especially in the contexts of smoothing and extraction of fundamental components of signals. G+Cpatterns occur at different lengths (scales) and, for this reason, G+Cplots are usually difficult to interpret. Current methods for genome analysis choose a window size and compute a \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \({\chi}^{2}\) \end{document}statistics of the average value for each window with respect to the whole genome.

Results: Firstly, wavelets are used to smooth G+Cprofiles to locate characteristic patterns in genome sequences. The method we use is based on performing a \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \({\chi}^{2}\) \end{document}statistics on the wavelet coefficients of a profile; thus we do not need to choose a fixed window size, in that the smoothing occurs at a set of different scales. Secondly, a wavelet scalogram is used as a measure for sequence profile comparison; this tool is very general and can be applied to other sequence profiles commonly used in genome analysis. We show applications to the analysis of Deinococcus radiodurans chromosome I, of two strains of Helicobacter pylori (26695, J99) and two of Neisseria meningitidis (serogroup B strain MC58 and serogroup A strain Z2491). We report a list of loci that have different G+Ccontent with respect to the nearby regions; the analysis of N. meningitidis serogroup B shows two new large regions with low G+Ccontent that are putative pathogenicity islands.

Availability: Software and numerical results (profiles, scalograms, high and low frequency components) for all the genome sequences analyzed are available upon request from the authors.

Contact: p.lio@zoo.cam.ac.uk

To whom correspondence should be addressed.
Homology-based gene structure prediction: simplified matching
algorithm using a translated codon (tron) and improved accuracy by
allowing for long gaps
Authors: Gotoh Osamu
Published: July 2002

Motivation: Locating protein-coding exons (CDSs) on a eukaryotic genomic DNA sequence is the initial and an essential step in predicting the functions of the genes embedded in that part of the genome. Accurate prediction of CDSs may be achieved by directly matching the DNA sequence with a known protein sequence or profile of a homologous family member(s).

Results: A new convention for encoding a DNA sequence into a series of 23 possible letters (translated codon or tron code) was devised to improve this type of analysis. Using this convention, a dynamic programming algorithm was developed to align a DNA sequence and a protein sequence or profile so that the spliced and translated sequence optimally matches the reference the same as the standard protein sequence alignment allowing for long gaps. The objective function also takes account of frameshift errors, coding potentials, and translational initiation, termination and splicing signals. This method was tested on Caenorhabditis elegans genes of known structures. The accuracy of prediction measured in terms of a correlation coefficient (CC) was about 95% at the nucleotide level for the 288 genes tested, and 97.0% for the 170 genes whose product and closest homologue share more than 30% identical amino acids. We also propose a strategy to improve the accuracy of prediction for a set of paralogous genes by means of iterative gene prediction and reconstruction of the reference profile derived from the predicted sequences.

Availability: The source codes for the program ‘aln’ written in ANSI-C and the test data will be available via anonymous FTP at ftp.genome.ad.jp/pub/genomenet/saitama-cc.

Contact: gotoh@cancer-c.pref.saitama.jp
Automatic discovery of regulatory patterns in promoter regions
based on whole cell expression data and functional annotation
Authors: Juhl Jensen Lars , Knudsen Steen
Published: July 2002

Motivation: The whole genomes submitted to GenBank contain valuable information about the function of genes as well as the upstream sequences and whole cell expression provides valuable information on gene regulation. To utilize these large amounts of data for a biological understanding of the regulation of gene expression, new automatic methods for pattern finding are needed.

Results: Two word-analysis algorithms for automatic discovery of regulatory sequence elements have been developed. We show that sequence patterns correlated to whole cell expression data can be found using Kolmogorov–Smirnov tests on the raw data, thereby eliminating the need for clustering co-regulated genes. Regulatory elements have also been identified by systematic calculations of the significance of correlations between words found in the functional annotation of genes and DNA words occuring in their promoter regions. Application of these algorithms to the Saccharomyces cerevisiae genome and publicly available DNA array data sets revealed a highly conserved 9-mer occuring in the upstream regions of genes coding for proteasomal subunits. Several other putative and known regulatory elements were also found.

Availability: Upon request.

Contact: steen@cbs.dtu.dk
TrExML: a maximum-likelihood approach for extensive tree-space
exploration
Authors: Wolf Marty J. , Easteal Simon , Kahn Margaret , McKay Brendan D. , Jermiin Lars S.
Published: July 2002

Motivation: Maximum-likelihood analysis of nucleotide and amino acid sequences is a powerful approach for inferring phylogenetic relationships and for comparing evolutionary hypotheses. Because it is a computationally demanding and time-consuming process, most algorithms explore only a minute portion of tree-space, with the emphasis on finding the most likely tree while ignoring the less likely, but not significantly worse, trees. However, when such trees exist, it is equally important to identify them to give due consideration to the phylogenetic uncertainty. Consequently, it is necessary to change the focus of these algorithms such that near optimal trees are also identified.

Results: This paper presents the Advanced Stepwise Addition Algorithmfor exploring tree-space and two algorithms for generating all binary trees on a set of sequences. The Advanced Stepwise Addition Algorithm has been implemented in TrExML, a phylogenetic program for maximum-likelihood analysis of nucleotide sequences. TrExML is shown to be more effective at finding near optimal trees than a similar program, fastDNAml, implying that TrExML offers a better approach to account for phylogenetic uncertainty than has previously been possible. A program, TreeGen, is also described; it generates binary trees on a set of sequences allowing for extensive exploration of tree-space using other programs.

Availability: TreeGen, TrExML, and the sequence data used to test the programs are available from the following two WWW sites: http://whitetail.bemidji.msus.edu/trexml/and http://jcsmr.anu.edu.au/dmm/humgen.html.

Contact: mjwolf@whitetail.bemidji.msus.edu; Simon.Easteal@anu.edu.au; Margaret.Kahn@anu.edu.au; bdm@cs.anu.edu.au; jermiin@angis.usyd.edu.au
NAIL—Network Analysis Interface for Linking HMMER results
Authors: Sánchez-Pulido Luis , Yuan Yan P. , Andrade Miguel A. , Bork Peer
Published: July 2002

Summary: Network Analysis Interface for Linking HMMER results (NAIL) is a web-based tool for the analysis of results from a HMMER protein database-search. NAIL facilitates the selection of protein hits and the creation of an alignment, which can be used for a new sequence similarity search.

Availability: From http://www.bork.embl-heidelberg.de/NAIL/

Contact: sanchez@cnb.uam.es

* To whom correspondence should be addressed.
Selection of optimal DNA oligos for gene expression arrays
Authors: Li Fugen , Stormo Gary D.
Published: July 2002

Motivation: High density DNA oligo microarrays are widely used in biomedical research. Selection of optimal DNA oligos that are deposited on the microarrays is critical. Based on sequence information and hybridization free energy, we developed a new algorithm to select optimal short (20–25 bases) or long (50 or 70 bases) oligos from genes or open reading frames (ORFs) and predict their hybridization behavior. Having optimized probes for each gene is valuable for two reasons. By minimizing background hybridization they provide more accurate determinations of true expression levels. Having optimum probes minimizes the number of probes needed per gene, thereby decreasing the cost of each microarray, raising the number of genes on each chip and increasing its usage.

Results: In this paper we describe algorithms to optimize the selection of specific probes for each gene in an entire genome. The criteria for truly optimum probes are easily stated but they are not computable at all levels currently. We have developed an heuristic approach that is efficiently computable at all levels and should provide a good approximation to the true optimum set. We have run the program on the complete genomes for several model organisms and deposited the results in a database that is available on-line (http://ural.wustl.edu/~lif/probe.pl).

Availability: The program is available upon request.

Contact: lif@ural.wustl.edu; stormo@ural.wustl.edu
MELTING, computing the melting temperature of nucleic acid
duplex
Authors: Le
   Novère Nicolas
Published: July 2002

Summary: MELTING computes the enthalpy and entropy of an oligonucleotide duplex helix–coil transition, and then its melting temperature. The program uses the method of nearest-neighbours. The set of thermodynamic parameters can be easily customized. The program provides several correction methods for the concentration of salt. MELTING is a free program, available at no cost and open-source. Perl scripts are provided to show how MELTING can be used to construct more ambitious programs.

Availability: MELTING is available for several platforms (http://www.pasteur.fr/recherche/unites/neubiomol/meltinghome.html) and is accessible via a www server (http://bioweb.pasteur.fr/seqanal/interfaces/melting.html).

Contact: nl223@cus.cam.ac.uk
3Dee: a database of protein structural domains
Authors: Siddiqui Asim S. , Dengler Uwe , Barton Geoffrey J.
Published: July 2002

Summary: The 3Dee database is a repository of protein structural domains. It stores alternative domain definitions for the same protein, organises domains into sequence and structural hierarchies, contains non-redundant set(s) of sequences and structures, multiple structure alignments for families of domains, and allows previous versions of the database to be regenerated.

Availability: 3Dee is accessible on the World Wide Web at the URL http://barton.ebi.ac.uk/servers/3Dee.html

Contact: geoff@ebi.ac.uk; http://barton.ebi.ac.uk

* To whom correspondence should be addressed. Present address: EMBL-European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK.
Mining literature for protein–protein interactions
Authors: Marcotte Edward M. , Xenarios Ioannis , Eisenberg David
Published: July 2002

Motivation: A central problem in bioinformatics is how to capture information from the vast current scientific literature in a form suitable for analysis by computer. We address the special case of information on protein–protein interactions, and show that the frequencies of words in Medline abstracts can be used to determine whether or not a given paper discusses protein–protein interactions. For those papers determined to discuss this topic, the relevant information can be captured for the Database of Interacting Proteins. Furthermore, suitable gene annotations can also be captured.

Results: Our Bayesian approach scores Medline abstracts for probability of discussing the topic of interest according to the frequencies of discriminating words found in the abstract. More than 80 discriminating words (e.g. complex, interaction, two-hybrid) were determined from a training set of 260 Medline abstracts corresponding to previously validated entries in the Database of Interacting Proteins. Using these words and a log likelihood scoring function, \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \({\sim}\) \end{document}2000 Medline abstracts were identified as describing interactions between yeast proteins. This approach now forms the basis for the rapid expansion of the Database of Interacting Proteins.

Contact: marcotte@icmb.utexas.edu; ixenario@mbi.ucla.edu; david@mbi.ucla.edu

* These authors contributed equally to this work.
Adjustments and measures of differential expression for
microarray data
Authors: Tsodikov A. , Szabo A. , Jones D.
Published: July 2002

Motivation: Existing analyses of microarray data often incorporate an obscure data normalization procedure applied prior to data analysis. For example, ratios of microarray channels intensities are normalized to have common mean over the set of genes. We made an attempt to understand the meaning of such procedures from the modeling point of view, and to formulate the model assumptions that underlie them. Given a considerable diversity of data adjustment procedures, the question of their performance, comparison and ranking for various microarray experiments was of interest.

Results: A two-step statistical procedure is proposed: data transformation (adjustment for slide-specific effect) followed by a statistical test applied to transformed data. Various methods of analysis for differential expression are compared using simulations and real data on colon cancer cell lines. We found that robust categorical adjustments outperform the ones based on a precisely defined stochastic model, including some commonly used procedures.

Availability: A program implementing the proposed adjustment and test procedures is available at http://www.hci.utah.edu/groups/biostat/szabo.html.

Contact: alexander.tsodikov@hci.utah.edu

* To whom correspondence should be addressed.
Transcriptional regulation of human insulin receptor gene by the high‐mobility group protein HMGI(Y)
Authors: BRUNETTI ANTONIO , MANFIOLETTI GUIDALBERTO , CHIEFARI EUSEBIO , GOLDFINE IRA D. , FOTI DANIELA
Published: July 2002

We have previously identified two closely related nuclear binding proteins that specifically interact with two unique functional AT‐rich sequences of the 5′ regulatory region of the human insulin receptor gene. Expression of these nuclear binding proteins increases during myocyte and adipocyte differentiation, and in other tissues appears to correlate with insulin receptor content. We have hypothesized, therefore, that insulin receptor expression in the insulin target tissues is regulated at least in part by these nuclear proteins. Here we show data on purification and biochemical characterization of these DNA binding proteins. Using a conventional chromatographic purification procedure combined with electrophoresis mobility shift assay and immunoblot analyses, a unique ~15 kDa protein, either identical to or highly related to the architectural transcription factor HMGI(Y), has now been identified, suggesting an essential role for HMGI(Y) in regulating insulin receptor gene transcription. Direct evidence of HMGI(Y) insulin receptor promoter interactions is provided by functional analysis with the CAT reporter gene and by hormone binding studies in cells expressing HMGI(Y) antisense RNA. In these experiments, antisense HMGI(Y) specifically inhibits insulin receptor promoter function and insulin receptor protein expression, indicating that HMGI(Y) is required for proper transcription of insulin receptor gene. Moreover, our data consistently support the hypothesis that a putative defect in this nuclear binding protein may cause insulin receptor dysfunction with subsequent impairment of insulin signaling and action.—Brunetti, A., Manfioletti, G., Chiefari, E., Goldfine, I. D., Foti, D. Transcriptional regulation of human insulin receptor gene by the high‐mobility group protein HMGI(Y). FASEB J. 15, 492‐500 (2001)
The so-called Great Spanish Influenza Pandemic of 1918 may have originated in France in 1916
Authors: Oxford J. S.
Published: July 2002

This discussion piece examines the likely epicentre of the influenza pandemic of 1918–1919. Contrary to previous studies that have proposed a Chinese origin, there is documentation that suggests that, in this instance, the virus spread eastwards to China from Europe. Although more recent oubreaks of influenza have undoubtedly had an Oriental origin, the evidence indicates that future outbreaks could conceivably arise anywhere in the world.
Arabidopsis COP10 is a ubiquitin-conjugating enzyme variant that acts together with COP1 and the COP9 signalosome in repressing photomorphogenesis
Authors: Suzuki Genki , Yanagawa Yuki , Kwok Shing F. , Matsui Minami , Deng Xing-Wang
Published: July 2002

A group of evolutionarily conserved pleiotropic COP/DET/FUS proteins was initially defined by their ability to repress photomorphogenesis in Arabidopsis. It was proposed that this regulation be mediated by targeting degradation of key cellular regulators that promote photomorphogenesis. Among them, COP1 and the COP9 signalosome have been hypothesized to fulfill the roles as an ubiquitin ligase (E3) and an essential E3 modulator. Here we report that COP10 encodes a protein similar to ubiquitin-conjugating enzyme (E2) variant proteins (UEV). COP10 is part of a nuclear protein complex and capable of directly interacting with both COP1 and the COP9 signalosome. Our data indicates that COP10 defines a possible E2 activity, thus validating the working hypothesis that the pleiotropic COP/DET/FUS group of proteins defined a protein ubiquitination pathway.
Genomes in Flux: The Evolution of Archaeal and Proteobacterial Gene Content
Authors: Snel Berend , Bork Peer , Huynen Martijn A.
Published: July 2002

In the course of evolution, genomes are shaped by processes like gene loss, gene duplication, horizontal gene transfer, and gene genesis (the de novo origin of genes). Here we reconstruct the gene content of ancestral Archaea and Proteobacteria and quantify the processes connecting them to their present day representatives based on the distribution of genes in completely sequenced genomes. We estimate that the ancestor of the Proteobacteria contained around 2500 genes, and the ancestor of the Archaea around 2050 genes. Although it is necessary to invoke horizontal gene transfer to explain the content of present day genomes, gene loss, gene genesis, and simple vertical inheritance are quantitatively the most dominant processes in shaping the genome. Together they result in a turnover of gene content such that even the lineage leading from the ancestor of the Proteobacteria to the relatively large genome of Escherichia coli has lost at least 950 genes. Gene loss, unlike the other processes, correlates fairly well with time. This clock-like behavior suggests that gene loss is under negative selection, while the processes that add genes are under positive selection.
Metallochaperones and Metal-Transporting ATPases: A Comparative Analysis of Sequences and Structures
Authors: Arnesano Fabio , Banci Lucia , Bertini Ivano , Ciofi-Baffoni Simone , Molteni Elena , Huffman David L. , O'Halloran Thomas V.
Published: July 2002

A comparative structural genomic analysis of a new class of metal-trafficking proteins can provide insights into the intracellular chemistry of reactive cofactors such as copper and zinc. Starting from the sequences of the metallochaperone Atx1 and from the first soluble domain of the copper-transporting ATPase Ccc2, both from yeast, a search on the available genomes was performed using a homology criterion and a metal-binding motif x‘-x"-C-x‴-x⁗-C. By limiting ourselves to 20% identity with any of the proteins found, several soluble copper-transport proteins were identified, as well as soluble domains of membrane-bound ATPases. Structural models were calculated using high-resolution solution structures as templates, and the models were validated using statistical and energy criteria. Residue conservation and substitution have been interpreted and discussed in terms of structure–function relationship. The potential energy surfaces have been analyzed in terms of protein–protein interactions. We find that metallochaperones and their physiological partner ATPases from several phylogenetic kingdoms recognize one another, via an interplay of electrostatics, hydrogen bonding, and hydrophobic interactions, in a manner that precisely orients the metal-binding side chains for rapid metal transfer between otherwise tight binding sites. Finally, other putative metal-transport proteins are mentioned that have low homology and/or a different metal-binding consensus motif and that appear to use similar structures for recognition and transfer. This analysis highlights the wealth and the complexity of the field.
GeneLynx: A Gene-Centric Portal to the Human Genome
Authors: Lenhard Boris , Hayes William S. , Wasserman Wyeth W.
Published: July 2002

GeneLynx is a meta-database providing an extensive collection of hyperlinks to human gene-specific information in diverse databases available on the Internet. The GeneLynx project is based on the simple notion that given any gene-specific identifier (accession number, gene name, text, or sequence), scientists should be able to access a single location that provides a set of links to all the publicly available information pertinent to the specified human gene. GeneLynx was implemented as an extensible relational database with an intuitive and user-friendly Web interface. The data are automatically extracted from more than 40 external resources, using appropriate approaches to maximize coverage of the available data. Construction and curation of the system is mediated by a custom set of software tools. An indexing utility is provided to facilitate the establishment of hyperlinks in external databases. A unique feature of the GeneLynx system is a communal curation system for user-aided annotation. GeneLynx can be accessed freely at http://www.genelynx.org.
Fully Automatic Quantification of Microarray Image Data
Authors: Jain Ajay N. , Tokuyasu Taku A. , Snijders Antoine M. , Segraves Richard , Albertson Donna G. , Pinkel Daniel
Published: July 2002

DNA microarrays are now widely used to measure expression levels and DNA copy number in biological samples. Ratios of relative abundance of nucleic acids are derived from images of regular arrays of spots containing target genetic material to which fluorescently labeled samples are hybridized. Whereas there are a number of methods in use for the quantification of images, many of the software systems in wide use either encourage or require extensive human interaction at the level of individual spots on arrays. We present a fully automatic system for microarray image quantification. The system automatically locates both subarray grids and individual spots, requiring no user identification of any image coordinates. Ratios are computed based on explicit segmentation of each spot. On a typical image of 6000 spots, the entire process takes less than 20 sec. We present a quantitative assessment of performance on multiple replicates of genome-wide array-based comparative genomic hybridization experiments. By explicitly identifying the pixels in each spot, the system yields more accurate estimates of ratios than systems assuming spot circularity. The software, called UCSF Spot, runs on Windows platforms and is available free of charge for academic use.
The Genome of M. acetivorans Reveals Extensive Metabolic and Physiological Diversity
Authors: Galagan James E. , Nusbaum Chad , Roy Alice , Endrizzi Matthew G. , Macdonald Pendexter , FitzHugh Will , Calvo Sarah , Engels Reinhard , Smirnov Serge , Atnoor Deven , Brown Adam , Allen Nicole , Naylor Jerome , Stange-Thomann Nicole , DeArellano Kurt , Johnson Robin , Linton Lauren , McEwan Paul , McKernan Kevin , Talamas Jessica , Tirrell Andrea , Ye Wenjuan , Zimmer Andrew , Barber Robert D. , Cann Isaac , Graham David E. , Grahame David A. , Guss Adam M. , Hedderich Reiner , Ingram-Smith Cheryl , Kuettner H. Craig , Krzycki Joseph A. , Leigh John A. , Li Weixi , Liu Jinfeng , Mukhopadhyay Biswarup , Reeve John N. , Smith Kerry , Springer Timothy A. , Umayam Lowell A. , White Owen , White Robert H. , de Macario Everly Conway , Ferry James G. , Jarrell Ken F. , Jing Hua , Macario Alberto J.L. , Paulsen Ian , Pritchett Matthew , Sowers Kevin R. , Swanson Ronald V. , Zinder Steven H. , Lander Eric , Metcalf William W. , Birren Bruce
Published: July 2002

Methanogenesis, the biological production of methane, plays a pivotal role in the global carbon cycle and contributes significantly to global warming. The majority of methane in nature is derived from acetate. Here we report the complete genome sequence of an acetate-utilizing methanogen, Methanosarcina acetivorans C2A. Methanosarcineae are the most metabolically diverse methanogens, thrive in a broad range of environments, and are unique among the Archaea in forming complex multicellular structures. This diversity is reflected in the genome ofM. acetivorans. At 5,751,492 base pairs it is by far the largest known archaeal genome. The 4524 open reading frames code for a strikingly wide and unanticipated variety of metabolic and cellular capabilities. The presence of novel methyltransferases indicates the likelihood of undiscovered natural energy sources for methanogenesis, whereas the presence of single-subunit carbon monoxide dehydrogenases raises the possibility of nonmethanogenic growth. Although motility has not been observed in any Methanosarcineae, a flagellin gene cluster and two complete chemotaxis gene clusters were identified. The availability of genetic methods, coupled with its physiological and metabolic diversity, makes M. acetivorans a powerful model organism for the study of archaeal biology.

[Sequence, data, annotations, and analyses are available athttp://www-genome.wi.mit.edu/. The sequence data described in this paper have been submitted to the GenBank data library under accession no. AE010299.]
A structural basis for processivity
Authors: Breyer Wendy A. , Matthews Brian W.
Published: July 2002

The structures of a number of processive enzymes have been determined recently. These proteins remain attached to their polymeric substrates and may perform thousands of rounds of catalysis before dissociating. Based on the degree of enclosure of the substrate, the structures fall into two broad categories. In one group, the substrate is partially enclosed, while in the other class, enclosure is complete. In the latter case, enclosure is achieved by way of an asymmetric structure for some enzymes while others use a symmetrical toroid. In those cases where the protein completely encloses its polymeric substrate, the two are topologically linked and an immediate explanation for processivity is provided. In cases where there is only partial enclosure, the structural basis for processivity is less obvious. There are, for example, pairs of proteins that have quite similar structures but differ substantially in their processivity. It does appear, however, that the enzymes that are processive tend to be those that more completely enclose their substrates. In general terms, proteins that do not use topological restraint appear to achieve processivity by using a large interaction surface. This allows the enzyme to bind with moderate affinity at a multitude of adjacent sites distributed along its polymeric substrate. At the same time, the use of a large interaction surface minimizes the possibility that the enzyme might bind at a small number of sites with much higher affinity, which would interfere with sliding. Proteins that can both slide along a polymeric substrate, and, as well, recognize highly specific sites (e.g., some site‐specific DNA‐binding proteins) appear to undergo a conformational change between the cognate and noncognate‐binding modes.
Breaking the singleton of germination protease
Authors: Pei Jimin , Grishin Nick V.
Published: July 2002

Germination protease (GPR) plays an important role in the germination of spores of Bacillus and Clostridium species. A few very similar GPRs form a singleton group without significant sequence similarities to any other proteins. Their active site locations and catalytic mechanisms are unclear, despite the recent 3‐D structure determination of Bacillus megaterium GPR. Using structural comparison and sequence analysis, we show that GPR is homologous to bacterial hydrogenase maturation protease (HybD). HybD's activity relies on the recognition and binding of metal ions in Ni–Fe hydrogenase, its substrate. Two highly conserved motifs are shared among GPRs, hydrogenase maturation proteases, and another group of hypothetical proteins. Conservation of two acidic residues in all these homologs indicates that metal binding is important for their function. Our analysis helps localize the active site of GPRs and provides insight into the catalytic mechanisms of a superfamily of putative metal‐regulated proteases.
Standing, walking, running, and jumping on a force plate
Authors: Cross Rod
Published: July 2002

Details are given of an inexpensive force plate designed to measure ground reaction forces involved in human movement. Such measurements provide interesting demonstrations of relations between displacement, velocity, and acceleration, and illustrate aspects of mechanics that are not normally encountered in a conventional mechanics course, or that are more commonly associated with inanimate objects. When walking, the center of mass follows a curved path. The centripetal force is easily measured and it provides an upper limit to the speed at which a person can walk. When running, the legs behave like simple springs and the center of mass follows a path that is the same as that of a perfectly elastic bouncing ball.
Determination of the elastic constants of a composite plate using wavelet transforms and neural networks
Authors: Yang Jing , Cheng Jianchun , Berthelot Yves H.
Published: July 2002

An inverse method based on a combination of the wavelet transform and artificial neural networks is presented. The method is used to recover the elastic constants of a fiber-reinforced composite plate from experimental measurements of ultrasonic Lamb waves generated and detected with lasers. In this method, the elastic constants are not recovered from the dispersion curves but rather directly from the measured waveforms. Transient waveforms obtained by numerical simulations for different elastic constants are used as input to train the neural network. The wavelet transform is used to extract the eigenvectors from the Lamb wave signals to simplify the structure of the neutral network. The eigenvectors are then introduced into a multilayer internally recurrent neural network with a back-propagation algorithm. Finally, experimental waveforms recoded on a titanium-graphite composite plate are used as input to recover the elastic constants of the material.
On the combined effects of signal-to-noise ratio and room acoustics on speech intelligibility
Authors: Bradley J. S. , Reich R. D. , Norcross S. G.
Published: July 2002

Speech intelligibility in rooms is influenced by room acoustics effects and by the signal-to-noise ratio (S/N) of the speech and ambient noise. Several measures such as useful-to-detrimental sound ratios and the speech transmission index predict the combined effects of both types of factors. These measures were evaluated relative to speech intelligibility test results obtained in simulated sound fields. The use of simulated sound fields made it possible to create the full range of combinations of room acoustics and S/N effects likely to be found in rooms for speech. The S/N aspect is shown to be much more important than room acoustics effects and new broadband useful-to-detrimental ratios were validated. Useful-to-detrimental ratios, speech transmission index measures, and values of the articulation loss for consonants were all reasonably accurate predictors of speech intelligibility. Further improvements to these combined measures are suggested.
Range-dependent matched-field inversion of SWellEX-96 data using the downhill simplex algorithm
Authors: Musil Martin , Chapman N. Ross , Wilmut Michael J.
Published: July 2002

Matched-field inversion (MFI) techniques have been applied for effective and efficient estimation of geoacoustic parameters of the ocean bottom. This paper presents a new tomographic MFI method for use in range-dependent environments. The MFI correlates modeled data with measured data and uses a search algorithm to determine model parameter values that maximize the correlator. In the present method, a parabolic equation propagation model is used to compute replica fields to account for mode coupling in the environment. The search algorithm is a two-stage hybrid method that combines an initial global component and a final local component. The first stage employs a random search to determine N+1 parameter sets with the best correlations, where N is the number of parameters being determined. In the next stage the N+1 sets are used as inputs to the local downhill simplex algorithm. The algorithm is shown to perform well for simulated vertical line array data for an environment representative of the SWellEX-96 experimental site. The inversion technique is then applied to measured data obtained from a radial track in SWellEX-96. The geometric parameters of the experiment and dominant geoacoustic parameters were successfully recovered for data with relatively low signal-to-noise ratio.
Financial Disclosures Reported by Industry Among Authors of the American Academy of Ophthalmology Clinical Practice Guidelines
Authors: Nguyen Anne Xuan-Lan , Joly-Chevrier Maxine , Nguyen David-Dan , Wu Albert Y.
Published: March 2023

Importance

Recommendations of clinical guidelines affect physicians’ care delivery. Potential bias and undeclared conflicts of interests (COIs) among guideline authors can impact clinical practice decisions.

Objective

To assess financial disclosures reported by physician authors of the American Academy of Ophthalmology (AAO) Practice Pattern Guidelines compared with those reported by industry to evaluate the disclosures’ accuracy.

Design, Setting, and Participants

In this cross-sectional study, all clinical guidelines in the AAO Preferred Practice Patterns (PPP) since 2013 (first year with publicly available industry payment reports) were reviewed on May 1, 2022. Guideline physician authors’ name and their reported COI disclosure were extracted from the guideline publication. Payments to physician authors reported by industry were retrieved from the US Centers for Medicare & Medicaid Open Payments database. Physician authors serving on the AAO guideline committee were included.

Main Outcomes and Measures

The primary outcome measure was the accuracy of authors’ COIs disclosure. Secondary outcome measures were payments to physician authors reported by industry, the types of payments, and authors’ gender.

Results

A total of 24 AAO guidelines released between 2016 and 2020 were included. Per guideline, there was a mean (SD) of 7.83 (2.24) physician authors. After removing 14 nonphysician authors, 188 physician author names remained, including 83 names assigned as women (44.1%) and 105 names assigned as men (55.9%). Authors could be counted multiple times in these 188 names. According to the Open Payments database, industry reported that 112 of 188 physician authors (59.6%) had at least received 1 payment while serving on the guideline committee, with a payment mean (SD) of $29 849.35 ($54 131.56). According to AAO guidelines, 149 authors (79.3%) had no financial disclosures while serving on the guideline committee. Among these 149 authors, most authors (81 [54.4%]) had payments reported by industry on the Open Payments database not disclosed within the guideline reports. Women physicians were paid significantly more than men for total payments (median [IQR] payments, $15 265 [$598.47-$41 104.67] vs $301.48 [$218.85-$14 615.09]; difference, $14 963.52; P = .003).

Conclusions and Relevance

Industry reported physician guideline authors to have received significant industry payments, some of which were not disclosed within information of the guidelines. To strengthen author transparency regarding these reported disclosures, the authors may want to review and resolve such potential discrepancies during the review and subsequent publication of guidelines.
Injectable, Self‐Contained, Subaqueously Cross‐Linking Laminous Adhesives for Biophysical‐Chemical Modulation of Osteochondral Microenvironment
Authors: Xu Tianpeng , Yang Yuhe , Yeung Elton Hau‐Lam , Chen Qunchao , Bei Ho‐Pan , Yang Qiang , Yang Mo , Hao Yuefeng , Li Bin , Zhao Xin
Published: March 2023

Current osteochondral (OC) defect repair approaches using premade scaffolds face clinical limitations due to invasiveness, weak integrity, and/or insufficient interfacial bonding. An injectable hydrophobic laminous adhesive is developed that rapidly photocross‐link subaqueously and forms robust bi‐layered structure that orchestrates biophysical‐chemical cues for stimulating OC repair. Liquid hydrophobic photo‐cross‐linkable poly (lactide‐co‐propylene glycol‐co‐lactide) dimethacrylates (PmLnDMA) are adopted as cartilage phase and PmLnDMA encapsulating methacrylated hydroxyapatite nanoparticles (PmLnDMA/MH) as the mineralized subchondral bone phase. Both phases exhibit strong interfacial bonding due to the presence of “CC”. Mechanotransduction and growth factor‐mediated signaling pathways are enchanced by matching the mechanical properties of two phases to native cartilage and bone via systematical modulation of the adhesives’ composition and encapsulated growth factors’ release profile. This enhances mesenchymal stem cells’ commitment to corresponding chondrocytes and osteoblasts to augment OC repair in vitro and in vivo, and ultimately benefits patients suffering from OC fracture, osteoarthritis, and osteoporosis.
Multifunctional Coatings on Sulfide‐Based Solid Electrolyte Powders with Enhanced Processability, Stability, and Performance for Solid‐State Batteries
Authors: Hood Zachary D. , Mane Anil U. , Sundar Aditya , Tepavcevic Sanja , Zapol Peter , Eze Udochukwu D. , Adhikari Shiba P. , Lee Eungje , Sterbinsky George E. , Elam Jeffrey W. , Connell Justin G.
Published: March 2023

Sulfide‐based solid‐state electrolytes (SSEs) exhibit many tantalizing properties including high ionic conductivity and favorable mechanical properties for next‐generation solid‐state batteries. Widespread adoption of these materials is hindered by their intrinsic instability under ambient conditions, which makes them difficult to process at scale, and instability at the Li||SSE and cathode||SSE interfaces, which limits cell performance and lifetime. Atomic layer deposition is leveraged to grow thin Al2O3 coatings on Li6PS5Cl powders to address both issues simultaneously. These coatings can be directly grown onto Li6PS5Cl particles with negligible chemical modification of the underlying material and enable exposure of powders to pure and H2O‐saturated oxygen environments for ≥4 h with minimal reactivity, compared with significant degradation of the uncoated powder. Pellets fabricated from coated powders exhibit ionic conductivities up to 2× higher than those made from uncoated material, with a simultaneous decrease in electronic conductivity and significant suppression of chemical reactivity at the Li‐SSE interface. These benefits result in significantly improved room temperature cycle life at high capacity and current density. It is hypothesized that this enhanced performance derives from improved intergranular properties and improved Li metal adhesion. This work points to a completely new framework for designing active, stable, and scalable materials for next‐generation solid‐state batteries.