bluuebunny/crossref_metadata_2025 huggingface dataset:
Codon pairs in the genome of Escherichia coli
Authors: Boycheva Svetlana , Chkodrov Georgi , Ivanov Ivan
Published: May 2003

Motivation: The effect of two neighboring codons (codon pairs) on gene expression is mediated via the interaction of their cognate tRNAs occupying the two functional ribosomal sites during the translation elongation step. For steric reasons it is reasonable to assume that not all combinations of codons and therefore of tRNAs are equally favorable when situated on the ribosome surface. Aiming of identifying preferential and rare codon pairs, we have determined the frequency of occurrence of all possible combinations of codon pairs in the entire genome of Escherichia coli (E.coli).

Results: The frequency of occurrence of the 3904 codon pairs comprising both sense:sense and sense:stop codon pairs in the full set of E.coli 4289 ORFs was found to vary from zero to 4913 times. For most of the pairs we have observed a significant difference between the real and statistically predicted frequency of occurrence. The analysis of 334 highly expressed and 303 poorly expressed E.coli genes showed that codon pair usage is different for the two gene categories. Using an especially defined criterion (Δreg), the codon pairs are classified as ‘hypothetically attenuating’ (HAP) and ‘hypothetically non-attenuating’ (HNAP) and their possible effect on translation is discussed.

Availability: The program used in this study is available at http://www.bio21.bas.bg/codonpairs/

Contact: iviv@obzor.bio21.bas.bg; svetlana@obzor.bio21.bas.bg

* To whom correspondence should be addressed.
FPV: fast protein visualization using Java 3DTM
Authors: Can Tolga , Wang Yujun , Wang Yuan-Fang , Su Jianwen
Published: May 2003

Motivation: Many tools have been developed to visualize protein structures. Tools that have been based on Java 3D™ are compatible among different systems and they can be run remotely through web browsers. However, using Java 3D for visualization has some performance issues with it. The primary concerns about molecular visualization tools based on Java 3D are in their being slow in terms of interaction speed and in their inability to load large molecules. This behavior is especially apparent when the number of atoms to be displayed is huge, or when several proteins are to be displayed simultaneously for comparison.

Results: In this paper we present techniques for organizing a Java 3D scene graph to tackle these problems. We have developed a protein visualization system based on Java 3D and these techniques. We demonstrate the effectiveness of the proposed method by comparing the visualization component of our system with two other Java 3D based molecular visualization tools. In particular, for van der Waals display mode, with the efficient organization of the scene graph, we could achieve up to eight times improvement in rendering speed and could load molecules three times as large as the previous systems could.

Availability: FPV is freely available with source code at the following URL: http://www.cs.ucsb.edu/~tcan/fpv/

Contact: tcan@cs.ucsb.edu

* To whom correspondence should be addressed.
Terminology-driven mining of biomedical literature
Authors: Nenadic Goran , Spasic Irena , Ananiadou Sophia
Published: May 2003

Motivation: With an overwhelming amount of textual information in molecular biology and biomedicine, there is a need for effective literature mining techniques that can help biologists to gather and make use of the knowledge encoded in text documents. Although the knowledge is organized around sets of domain-specific terms, few literature mining systems incorporate deep and dynamic terminology processing.

Results: In this paper, we present an overview of an integrated framework for terminology-driven mining from biomedical literature. The framework integrates the following components: automatic term recognition, term variation handling, acronym acquisition, automatic discovery of term similarities and term clustering. The term variant recognition is incorporated into terminology recognition process by taking into account orthographical, morphological, syntactic, lexico-semantic and pragmatic term variations. In particular, we address acronyms as a common way of introducing term variants in biomedical papers. Term clustering is based on the automatic discovery of term similarities. We use a hybrid similarity measure, where terms are compared by using both internal and external evidence. The measure combines lexical, syntactical and contextual similarity. Experiments on terminology recognition and clustering performed on a corpus of Medline abstracts recorded the precision of 98 and 71% respectively.

Availability: Software for the terminology management is available upon request.

Contact: g.nenadic@umist.ac.uk

* To whom correspondence should be addressed at: Department of Computation/Department of BioMolecular Sciences, UMIST, Manchester, UK.
Inference of transcriptional regulation relationships
from gene expression data
Authors: Kwon Andrew T. , Hoos Holger H. , Ng Raymond
Published: May 2003

Motivation: In order to find gene regulatory networks from microarray data, it is important to first find direct regulatory relationships between pairs of genes.

Results: We propose a new method for finding potential regulatory relationships between pairs of genes from microarray time series data and apply it to expression data for cell-cycle related genes in yeast. We compare our algorithm, dubbed the event method, with the earlier correlation method and the edge detection method by Filkov et al. When tested on known transcriptional regulation genes, all three methods are able to find similar numbers of true positives. The results indicate that our algorithm is able to identify true positive pairs that are different from those found by the two other methods. We also compare the correlation and the event methods using synthetic data and find that typically, the event method obtains better results.

Availability: Software is available upon request.

Contact: hoos@cs.ubc.ca

* To whom correspondence should be addressed.
Approximate variance-stabilizing
transformations for gene-expression microarray data
Authors: Rocke David M. , Durbin Blythe
Published: May 2003

Motivation: A variance stabilizing transformation for microarray data was recently introduced independently by several research groups. This transformation has sometimes been called the generalized logarithm or glog transformation. In this paper, we derive several alternative approximate variance stabilizing transformations that may be easier to use in some applications.

Results: We demonstrate that the started-log and the log-linear-hybrid transformation families can produce approximate variance stabilizing transformations for microarray data that are nearly as good as the generalized logarithm (glog) transformation. These transformations may be more convenient in some applications.

Contact: dmrocke@ucdavis.edu

* To whom correspondence should be addressed.
ProPred1: prediction of promiscuous MHC Class-I binding
sites
Authors: Singh Harpreet , Raghava G.P.S.
Published: May 2003

Summary: ProPred1 is an on-line web tool for the prediction of peptide binding to MHC class-I alleles. This is a matrix-based method that allows the prediction of MHC binding sites in an antigenic sequence for 47 MHC class-I alleles. The server represents MHC binding regions within an antigenic sequence in user-friendly formats. These formats assist user in the identification of promiscuous MHC binders in an antigen sequence that can bind to large number of alleles. ProPred1 also allows the prediction of the standard proteasome and immunoproteasome cleavage sites in an antigenic sequence. This server allows identification of MHC binders, who have the cleavage site at the C terminus. The simultaneous prediction of MHC binders and proteasome cleavage sites in an antigenic sequence leads to the identification of potential T-cell epitopes.

Availability: Server is available at http://www.imtech.res.in/raghava/propred1/. Mirror site of this server is available at http://bioinformatics.uams.edu/mirror/propred1/

Supplementary information: Matrices and document on server are available at http://www.imtech.res.in/raghava/propred1/page2.html

Contact: raghava@imtech.res.in

* To whom correspondence should be addressed at Bioinformatics Centre, Institute of Microbial Technology, Sector 39A, Chandigarh, India.
Generating consensus sequences from partial
order multiple sequence alignment graphs
Authors: Lee Christopher
Published: May 2003

Motivation: Consensus sequence generation is important in many kinds of sequence analysis ranging from sequence assembly to profile-based iterative search methods. However, how can a consensus be constructed when its inherent assumption—that the aligned sequences form a single linear consensus—is not true?

Results: Partial Order Alignment (POA) enables construction and analysis of multiple sequence alignments as directed acyclic graphs containing complex branching structure. Here we present a dynamic programming algorithm (heaviest_bundle) for generating multiple consensus sequences from such complex alignments. The number and relationships of these consensus sequences reveals the degree of structural complexity of the source alignment. This is a powerful and general approach for analyzing and visualizing complex alignment structures, and can be applied to any alignment. We illustrate its value for analyzing expressed sequence alignments to detect alternative splicing, reconstruct full length mRNA isoform sequences from EST fragments, and separate paralog mixtures that can cause incorrect SNP predictions.

Availability: The heaviest_bundle source code is available at http://www.bioinformatics.ucla.edu/poa

Contact: leec@mbi.ucla.edu

* To whom correspondence should be addressed.
Pathways database system: an integrated system for biological pathways
Authors: Krishnamurthy L. , Nadeau J. , Ozsoyoglu G. , Ozsoyoglu M. , Schaeffer G. , Tasan M. , Xu W.
Published: May 2003

Motivation: During the next phase of the Human Genome Project, research will focus on functional studies of attributing functions to genes, their regulatory elements, and other DNA sequences. To facilitate the use of genomic information in such studies, a new modeling perspective is needed to examine and study genome sequences in the context of many kinds of biological information. Pathways are the logical format for modeling and presenting such information in a manner that is familiar to biological researchers.

Results: In this paper we present an integrated system, called Pathways Database System, with a set of software tools for modeling, storing, analyzing, visualizing, and querying biological pathways data at different levels of genetic, molecular, biochemical and organismal detail. The novel features of the system include: (a) genomic information integrated with other biological data and presented from a pathway, rather than from the DNA sequence, perspective; (b) design for biologists who are possibly unfamiliar with genomics, but whose research is essential for annotating gene and genome sequences with biological functions; (c) database design, implementation and graphical tools which enable users to visualize pathways data in multiple abstraction levels, and to pose predetermined queries; and (d) an implementation that allows for web(XML)-based dissemination of query outputs (i.e. pathways data) to researchers in the community, giving them control on the use of pathways data.

Availability: Available on request from the authors.

Contact: mxo2@po.cwru.edu

Supplementary information: http://nashua.cwru.edu/pathways

* To whom correspondence should be addressed.
Hierarchical analysis of dependency in metabolic networks
Authors: Gagneur Julien , Jackson David B. , Casari Georg
Published: May 2003

Motivation: Elucidation of metabolic networks for an increasing number of organisms reveals that even small networks can contain thousands of reactions and chemical species. The intimate connectivity between components complicates their decomposition into biologically meaningful sub-networks. Moreover, traditional higher-order representations of metabolic networks as metabolic pathways, suffers from the lack of rigorous definition, yielding pathways of disparate content and size.

Results: We introduce a hierarchical representation that emphasizes the gross organization of metabolic networks in largely independent pathways and sub-systems at several levels of independence. The approach highlights the coupling of different pathways and the shared compounds responsible for those couplings. By assessing our results on Escherichia coli (E.coli metabolic reactions, Genetic Circuits Research Group, University of California, San Diego, http://gcrg.ucsd.edu/organisms/ecoli.html,‘ model v 1.01. reactions’) against accepted biochemical annotations, we provide the first systematic synopsis of an organism’s metabolism. Comparison with operons of E.coli shows that low-level clusters are reflected in genome organization and gene regulation.

Availability: Source code, data sets and supplementary information are available at http://www.mas.ecp.fr/labo/equipe/gagneur/hierarchy/hierarchy.html

Contact: julien.gagneur@cellzome.com

* To whom correspondence should be addressed.

† Present address: Cellzome AG, Meyerhofstr. 1, 69117 Heidelberg, Germany..
Visual representation of database search results: the RHIMS Plot
Authors: Martin David M.A. , Hill Pamela , Barton Geoffrey J. , Flavell Andrew J.
Published: May 2003

Summary: An algorithm and software are described that provide a fast method to produce a novel, function-oriented visualization of the results of a sequence database search. Text mining of sequence annotations allows position specific plots of potential functional similarity to be compared in a simple compact representation.

Availability: The application can be accessed via a web server at http://www.compbio.dundee.ac.uk. The RHIMS software may be obtained by request to the authors.

Contact: d.m.a.martin@dundee.ac.uk

* To whom correspondence should be addressed.
Ligand-Info, searching for similar small compounds using
index profiles
Authors: von Grotthuss Marcin , Pas Jakub , Rychlewski Leszek
Published: May 2003

Motivation: The Ligand-Info system is based on the assumption that small molecules with similar structure have similar functional (binding) properties. The developed system enables a fast and sensitive index based search for similar compounds in large databases. Index profiles, constructed by averaging indexes of related molecules are used to increase the specificity of the search. The utilization of index profiles helps to focus on frequent, common features of a family of compounds.

Results: A Java-based tool for clustering and scanning of small molecules has been created. The tool can interactively cluster sets of molecules and create index profiles on the user side and automatically download similar molecules from a databases of 250 000 compounds. The results of the application of index profiles demonstrate that the profile based search strategy can increase the quality of the selection process.

Availability: The system is available at http://Ligand.Info. The application requires the Java Runtime Environment 1.4, which can be automatically installed during the first use on desktop systems, which support it. A standalone version of the program is available from the authors upon request.

Contact: leszek@bioinfo.pl

* To whom correspondence should be addressed.
Integrative approach for computationally inferring
protein domain interactions
Authors: Ng See-Kiong , Zhang Zhuo , Tan Soon-Heng
Published: May 2003

Motivation: The current need for high-throughput protein interaction detection has resulted in interaction data being generated en masse through such experimental methods as yeast-two-hybrids and protein chips. Such data can be erroneous and they often do not provide adequate functional information for the detected interactions. Therefore, it is useful to develop an in silico approach to further validate and annotate the detected protein interactions.

Results: Given that protein–protein interactions involve physical interactions between protein domains, domain–domain interaction information can be useful for validating, annotating, and even predicting protein interactions. However, large-scale, experimentally determined domain–domain interaction data do not exist. Here, we describe an integrative approach to computationally derive putative domain interactions from multiple data sources, including protein interactions, protein complexes, and Rosetta Stone sequences. We further prove the usefulness of such an integrative approach by applying the derived domain interactions to predict and validate protein–protein interactions.

Availability: A database of putative protein domain interactions derived using the method described in this paper is available at http://interdom.lit.org.sg.

Contact: skng@lit.org.sg

* To whom correspondence should be addressed.
Fuzzy C-means method for clustering microarray data
Authors: Dembélé Doulaye , Kastner Philippe
Published: May 2003

Motivation: Clustering analysis of data from DNA microarray hybridization studies is essential for identifying biologically relevant groups of genes. Partitional clustering methods such as K-means or self-organizing maps assign each gene to a single cluster. However, these methods do not provide information about the influence of a given gene for the overall shape of clusters. Here we apply a fuzzy partitioning method, Fuzzy C-means (FCM), to attribute cluster membership values to genes.

Results: A major problem in applying the FCM method for clustering microarray data is the choice of the fuzziness parameter m. We show that the commonly used value m = 2 is not appropriate for some data sets, and that optimal values for m vary widely from one data set to another. We propose an empirical method, based on the distribution of distances between genes in a given data set, to determine an adequate value for m. By setting threshold levels for the membership values, genes which are tigthly associated to a given cluster can be selected. Using a yeast cell cycle data set as an example, we show that this selection increases the overall biological significance of the genes within the cluster.

Availability: Supplementary text and Matlab functions are available at http://www-igbmc.u-strasbg.fr/fcm/

Contact: doulaye@titus.u-strasbg.fr

* To whom correspondence should be addressed.
Observing and interpreting correlations in metabolomic
networks
Authors: Steuer R. , Kurths J. , Fiehn O. , Weckwerth W.
Published: May 2003

Motivation: Metabolite profiling aims at an unbiased identification and quantification of all the metabolites present in a biological sample. Based on their pair-wise correlations, the data obtained from metabolomic experiments are organized into metabolic correlation networks and the key challenge is to deduce unknown pathways based on the observed correlations. However, the data generated is fundamentally different from traditional biological measurements and thus the analysis is often restricted to rather pragmatic approaches, such as data mining tools, to discriminate between different metabolic phenotypes.

Methods and Results: We investigate to what extent the data generated networks reflect the structure of the underlying biochemical pathways. The purpose of this work is 2-fold: Based on the theory of stochastic systems, we first introduce a framework which shows that the emergent correlations can be interpreted as a‘ fingerprint’ of the underlying biophysical system. This result leads to a systematic relationship between observed correlation networks and the underlying biochemical pathways. In a second step, we investigate to what extent our result is applicable to the problem of reverse engineering, i.e. to recover the underlying enzymatic reaction network from data. The implications of our findings for other bioinformatics approaches are discussed.

Contact: steuer@agnld.uni-potsdam.de

* To whom correspondence should be addressed.
ACGT—a comparative genomics tool
Authors: Xie Tao , Hood Leroy
Published: May 2003

Summary: ACGT (a comparative genomics tool) is a genomic DNA sequence comparison viewer and analyzer. It can read a pair of DNA sequences in GenBank, Embl or Fasta formats, with or without a comparison file, and provide users with many options to view and analyze the similarities between the input sequences. It is written in Java and can be run on Unix, Linux and Windows platforms.

Availability: The ACGT program is freely available with documentation and examples at website: http://db.systemsbiology.net/projects/local/mhc/acgt/

Contact: txie@systemsbiology.org

* To whom correspondence should be addressed.
Zerg: a very fast BLAST parser library
Authors: Paquola Apuã C.M. , Machado Abimael A. , Reis Eduardo M. , da Silva Aline M. , Verjovski-Almeida Sergio
Published: May 2003

Summary: Zerg is a library of sub-routines that parses the output from all NCBI BLAST programs (Blastn, Blastp, Blastx, Tblastn and Tblastx) and returns the attributes of a BLAST report to the user. It is optimized for speed, being especially useful for large-scale genomic analysis. Benchmark tests show that Zerg is over two orders of magnitude faster than some widely used BLAST parsers.

Availability: http://bioinfo.iq.usp.br/zerg

Contact: verjo@iq.usp.br

* To whom correspondence should be addressed.
Mining HIV dynamics using independent component analysis
Authors: Draghici Sorin , Graziano Frank , Kettoola Samira , Sethi Ishwar , Towfic George
Published: May 2003

Motivation: We implement a data mining technique based on the method of Independent Component Analysis (ICA) to generate reliable independent data sets for different HIV therapies. We show that this technique takes advantage of the ICA power to eliminate the noise generated by artificial interaction of HIV system dynamics. Moreover, the incorporation of the actual laboratory data sets into the analysis phase offers a powerful advantage when compared with other mathematical procedures that consider the general behavior of HIV dynamics.

Results: The ICA algorithm has been used to generate different patterns of the HIV dynamics under different therapy conditions. The Kohonen Map has been used to eliminate redundant noise in each pattern to produce a reliable data set for the simulation phase. We show that under potent antiretroviral drugs, the value of the CD4+ cells in infected persons decreases gradually by about 11% every 100 days and the levels of the CD8+ cells increase gradually by about 2% every 100 days.

Availability: Executable code and data libraries are available by contacting the corresponding author.

Implementation: Mathematica 4 has been used to simulate the suggested model. A Pentium III or higher platform is recommended.

Contact: gtowfic@clarke.edu.

* To whom correspondence should be addressed.
3D-Jury: a simple approach to improve protein structure predictions
Authors: Ginalski Krzysztof , Elofsson Arne , Fischer Daniel , Rychlewski Leszek
Published: May 2003

Motivation: Consensus structure prediction methods (meta-predictors) have higher accuracy than individual structure prediction algorithms (their components). The goal for the development of the 3D-Jury system is to create a simple but powerful procedure for generating meta-predictions using variable sets of models obtained from diverse sources. The resulting protocol should help to improve the quality of structural annotations of novel proteins.

Results: The 3D-Jury system generates meta-predictions from sets of models created using variable methods. It is not necessary to know prior characteristics of the methods. The system is able to utilize immediately new components (additional prediction providers). The accuracy of the system is comparable with other well-tuned prediction servers. The algorithm resembles methods of selecting models generated using ab initio folding simulations. It is simple and offers a portable solution to improve the accuracy of other protein structure prediction protocols.

Availability: The 3D-Jury system is available via the Structure Prediction Meta Server (http://BioInfo.PL/Meta/) to the academic community.

Contact: leszek@bioinfo.pl

Supplementary information: 3D-Jury is coupled to the continuous online server evaluation program, LiveBench (http://BioInfo.PL/LiveBench/)

* To whom correspondence should be addressed.
CAP: conformation angles package—displaying
the conformation angles of side chains in proteins
Authors: Sheik S. S. , Sundararajan P. , Shanthi V. , Sekar K.
Published: May 2003

Summary: A graphics package has been developed to display all side chain conformation angles of the user selected residue in a given protein structure. The proposed package is incorporated with all the protein structures (solved using X-ray diffraction and NMR spectroscopy) available in the Protein Data Bank. The package displays the multiple conformations adopted by a single amino acid residue whose structure is solved and refined at very high resolution. In addition, it shows the percentage distribution of the side chain conformation angles in different rotameric states.

Availability: http://144.16.71.146/cap/

Contact: sekar@physics.iisc.ernet.in

* To whom correspondence should be addressed.
Microarray standard data set and figures of merit
for comparing data processing methods and experiment designs
Authors: He Yudong D. , Dai Hongyue , Schadt Eric E. , Cavet Guy , Edwards Stephen W. , Stepaniants Sergey B. , Duenwald Sven , Kleinhanz Robert , Jones Allan R. , Shoemaker Daniel D. , Stoughton Roland B.
Published: May 2003

Motivation: There is a very large and growing level of effort toward improving the platforms, experiment designs, and data analysis methods for microarray expression profiling. Along with a growing richness in the approaches there is a growing confusion among most scientists as to how to make objective comparisons and choices between them for different applications. There is a need for a standard framework for the microarray community to compare and improve analytical and statistical methods.

Results: We report on a microarray data set comprising 204 in-situ synthesized oligonucleotide arrays, each hybridized with two-color cDNA samples derived from 20 different human tissues and cell lines. Design of the ∼ 24 000 60mer oligonucleotides that report ∼2500 known genes on the arrays, and design of the hybridization experiments, were carried out in a way that supports the performance assessment of alternative data processing approaches and of alternative experiment and array designs. We also propose standard figures of merit for success in detecting individual differential expression changes or expression levels, and for detecting similarities and differences in expression patterns across genes and experiments. We expect this data set and the proposed figures of merit will provide a standard framework for much of the microarray community to compare and improve many analytical and statistical methods relevant to microarray data analysis, including image processing, normalization, error modeling, combining of multiple reporters per gene, use of replicate experiments, and sample referencing schemes in measurements based on expression change.

Availability/Supplementary information: Expression data and supplementary information are available at http://www.rii.com/publications/2003/HE_SDS.htm

Contact: yudong_he@merck.com

* To whom correspondence should be addressed.

† A wholly owned subsidiary of Merck & Co., Inc.
Computation method to identify differential allelic gene expression
and novel imprinted genes
Authors: Yang Howard H. , Hu Ying , Edmonson Michael , Buetow Kenneth , Lee Maxwell P.
Published: May 2003

Motivation: Genomic imprinting plays an important role in both normal development and diseases. Abnormal imprinting is strongly associated with several human diseases including cancers. Most of the imprinted genes were discovered in the neighborhood of the known imprinted genes. This approach is difficult to extend to analyze the whole genome. We have decided to take a computational approach to systematically search the whole genome for the presence of mono-allelic expressed genes and imprinted genes in human genome.

Results: A computational method was developed to identify novel imprinted or mono-allelic genes. Individuals represented in human cDNA libraries were genotyped using Bayesian statistics, and differential expression of polymorphic alleles was identified. A significant reduction in the number of libraries that expressed both alleles, measured by Z-statistics, is a strong indicator for an imprinted or a mono-allelic gene.

Availability: The data sets are available at http://leelab.nci.nih.gov/leelab/jsp/IGDM/IGDM.html

Contact: leemax@mail.nih.gov.

Supplementary information: http://leelab.nci.nih.gov/leelab/jsp/IGDM/IGDM.html

* To whom correspondence should be addressed.
Corrected small-sample estimation of the Bayes error
Authors: Brun Marcel , Sabbagh David , Kim Seungchan , Dougherty Edward R.
Published: May 2003

Motivation: A major problem of pattern classification is estimation of the Bayes error when only small samples are available. One way to estimate the Bayes error is to design a classifier based on some classification rule applied to sample data, estimate the error of the designed classifier, and then use this estimate as an estimate of the Bayes error. Relative to the Bayes error, the expected error of the designed classifier is biased high, and this bias can be severe with small samples.

Results: This paper provides a correction for the bias by subtracting a term derived from the representation of the estimation error. It does so for Boolean classifiers, these being defined on binary features. Although the general theory applies to any Boolean classifier, a model is introduced to reduce the number of parameters. A key point is that the expected correction is conservative. Properties of the corrected estimate are studied via simulation. The correction applies to binary predictors because they are mathematically identical to Boolean classifiers. In this context the correction is adapted to the coefficient of determination, which has been used to measure nonlinear multivariate relations between genes and design genetic regulatory networks. An application using gene-expression data from a microarray experiment is provided on the website http://gspsnap.tamu.edu/smallsample/ (user:‘smallsample’, password:‘smallsample)’).

Contact: edward@ee.tamu.edu

* To whom correspondence should be addressed.
Monitoring Socioeconomic Inequalities in Sexually Transmitted Infections, Tuberculosis, and Violence: Geocoding and Choice of Area-Based Socioeconomic Measures—The Public Health Disparities Geocoding Project (US)
Authors: Krieger Nancy , Waterman Pamela D. , Chen Jarvis T. , Soobader Mah-Jabeen , Subramanian SV
Published: May 2003

Objectives.

To determine which area-based socioeconomic measures, at which level of geography, are suitable for monitoring socioeconomic inequalities in sexually transmitted infections (STIs), tuberculosis (TB), and violence in the United States.

Methods.

Cross-sectional analysis of public health surveillance data, geocoded and linked to area-based socioeconomic measures generated from 1990 census tract, block group, and ZIP Code data. We included all incident cases among residents of either Massachusetts (MA; 1990 population = 6,016,425) or Rhode Island (RI; 1990 population = 1,003,464) for: STIs (MA: 1994–1998, n = 26,535 chlamydia, 7,464 gonorrhea, 2,619 syphilis; RI: 1994–1996, n = 4,473 chlamydia, 1,256 gonorrhea, 305 syphilis); TB (MA: 1993–1998, n = 1,793; RI: 1985–1994, n = 576), and non-fatal weapons related injuries (MA: 1995–1997, n = 6,628).

Results.

Analyses indicated that: ( a) block group and tract socioeconomic measures performed similarly within and across both states, with results more variable for the ZIP Code level measures; ( b) measures of economic deprivation consistently detected the steepest socioeconomic gradients, considered across all outcomes (incidence rate ratios on the order of 10 or higher for syphilis, gonorrhea, and non-fatal intentional weapons-related injuries, and 7 or higher for chlamydia and TB); and ( c) results were similar for categories generated by quintiles and by a priori categorical cut-points.

Conclusions.

Supplementing U.S. public health surveillance systems with census tract or block group area-based socioeconomic measures of economic deprivation could greatly enhance monitoring and analysis of social inequalities in health in the United States.
Structure of lithium benzilate hemihydrate solved by simulated annealing and difference Fourier synthesis from powder data
Authors: Mora Asiloé J. , Fitch Andrew N. , Ramirez Belkis M. , Delgado Gerzon E. , Brunelli Michela , Wright Jonathan
Published: May 2003

The crystal structure of lithium benzilate hemihydrate (C14H11O_3^-Li+·0.5H2O) was solved from synchrotron powder diffraction data. This compound crystallizes in the monoclinic space group P21/a. The structure was solved via the direct space search for two benzilate fragments using the simulated-annealing program DASH, localization of the lithium ions and water molecule from a difference Fourier map, and a restrained Rietveld refinement (R
wp = 0.0687). The structure is a coordination polymer of [Li2(C14H11O3)2·H2O]2 tetramers building helical fourfold one-dimensional channels parallel to [010]. Inside the channels the tetrahedral coordination spheres of the lithium ions contain hydroxyl and carbonyl groups, and water molecules. The water molecule functions as the cohesive entity forming extended hydrogen-bonded chains running along [010], and bifurcated donor hydrogen bonds with the two nearest carboxylates. At the outer edge of the channels, weaker intermolecular C—H...Ph hydrogen bonds along [100] and [001] contribute to the supramolecular aggregation of the structure.
The Zintl–Klemm concept applied to cations in oxides. I. The structures of ternary aluminates
Authors: Santamaría-Pérez David , Vegas Angel
Published: May 2003

The structures of 94 ternary aluminates are reinterpreted on the basis of the Zintl–Klemm concept and Pearson's generalized octet rule. In aluminates of highly electropositive metals such as alkali, alkaline-earth and rare-earth metals, the Al atoms form three-dimensional skeleta which can be interpreted as if the Al atoms were behaving as Zintl polyanions, adopting the structure of either main-group elements or Zintl polyanions showing the same connectivity. The O atoms are then located close to both the hypothetical two-electron bonds and the lone pairs, giving rise to a tetrahedral coordination. When more electronegative elements, such as W or Si, are present in the compound, the electron transfer towards the Al atoms does not take place. In this case, aluminium behaves as a base, transferring its electrons to the more electronegative atoms and the coordination sphere of aluminium becomes octahedral. In some compounds the Al atoms clearly show amphoteric character so that some Al atoms act as donors (bases) and hence are octahedrally coordinated, whereas others behave as acceptors (acids), adopting a tetrahedral coordination. From this it is concluded that the coordination sphere of aluminium is not a function of the ionic radius of the Al3+ cations, but it depends on the nature of the other cations accompanying them in the structure. The networks formed by these aluminates are, in many instances, similar to those of the binary oxides of the main-group elements. For this reason, a systematic survey of these oxides is also reported. Compounds such as stuffed cristobalites and trydimites and also perovskites are examples of this new interpretation. Perovskites are then reinterpreted as a stuffed pseudo-TeO3 structure. Other families of compounds such as silicates and phosphates are susceptible to a similar interpretation. This study provides additional examples of how cations recognize themselves in spite of being embedded in an oxygen matrix.
The commensurate composite σ-structure of β-tantalum
Authors: Arakcheeva Alla , Chapuis Gervais , Birkedal Henrik , Pattison Phil , Grinevitch Vladimir
Published: May 2003

The single-crystal investigation of the self-hosting σ-structure of β-tantalum (β-Ta) at 120 K (low-temperature, LT, structure) and at 293 K (RT-I before cooling and RT-II after cooling and rewarming; RT represents room temperature) shows that this structure is indeed a specific two-component composite where the components have the same (or an integer multiple) lattice constants but different space groups. The space groups of both host (H) and guest (G) components cause systematic absences, which result from their intersection. The highest symmetry of a σ-structure can be described as [H: P42/mnm; G: P4/mbm (c

G
= 0.5c

H
); composite: P42/mnm]. A complete analysis of possible symmetries is presented in the Appendix. In β-Ta, two components modify their symmetry during the thermal process 293 K (RT-I) → 120 K (LT) → 293 K (RT-II): [H: P\bar 421
m; G: P\bar 421
m; composite: P\bar 421
m] → [H: P\bar 4, G: P4/mbm (c

G
= 0.5c

H
), composite: P\bar 4] → [H: P\bar 421
m, G: P4/mbm (c

G
= 0.5c

H
), composite: P\bar 421
m]. Thus, the phase transition is reversible with respect to H and irreversible with respect to G.
Sodium carbonate revisited
Authors: Dusek Michal , Chapuis Gervais , Meyer Mathias , Petricek Vaclav
Published: May 2003

We present the structure of anhydrous sodium carbonate at room temperature (phase γ) and 110 K (phase δ) based on single-crystal X-ray diffraction data. The incommensurate phase γ was determined almost 30 years ago in the harmonic approximation using one modulation wave and first-order satellites. In our work we use satellites up to fifth order and additional harmonic waves to model the anharmonic features of the structure. The commensurate phase δ is presented for the first time. Using the superspace approach, both phases are compared in order to find common trends in the whole range of the sodium carbonate phases. We present arguments supporting the hypothesis that the driving force of the phase transitions may originate in the unsaturated bonding potential of one of the Na ions.
Redetermination of the crystal structure of α-copper phthalocyanine grown on KCl
Authors: Hoshino Akitaka , Takenaka Yoshiko , Miyaji Hideki
Published: May 2003

The crystal structure of a polymorph of copper phthalocyanine (CuPc) grown on a KCl substrate is redetermined by transmission electron diffraction. It has a triclinic unit cell containing one molecule; the crystal does not have a herringbone-type molecular arrangement, which is a common packing mode of planar phthalocyanines. The molecular packing is determined by the diffraction intensity with the aid of the calculation of molecular packing energy. One of the striking features of this polymorph is its stacking mode within a molecular column: the molecular stacking direction projected on a molecular plane is different by an angle of about 45° from that of the α-modifications of platinum phthalocyanine (PtPc) and metal-free phthalocyanine (H2Pc). A powder X-ray diffraction profile calculated for the polymorph agrees well with that of so-called α-CuPc and Rietveld analysis for α-CuPc indicates that the CuPc crystals grown on KCl are actually α-CuPc; hence, α-CuPc is not isostructural with either α-PtPc or α-H2Pc. On the basis of the present results and the reported crystal structures of the planar phthalocyanines that form molecular columns, the polymorphs of the phthalocyanines can be classified into four types distinguished by the molecular stacking mode within the column: α(×)-, α(+)-, β(×)- and β(+)-types.
Fishing new proteins in the twilight zone of genomes: The test case of outer membrane proteins in Escherichia coli K12, Escherichia coli O157:H7, and other Gram‐negative bacteria
Authors: Casadio Rita , Fariselli Piero , Finocchiaro Giacomo , Martelli Pier Luigi
Published: May 2003

We address the problem of clustering the whole protein content of genomes into three different categories—globular, all‐α, and all‐β membrane proteins—with the aim of fishing new membrane proteins in the pool of nonannotated proteins (twilight zone). The focus is then mainly on outer membrane proteins. This is performed by using an integrated suite of programs (Hunter) specifically developed for predicting the occurrence of signal peptides in proteins of Gram‐negative bacteria and the topography of all‐α and all‐β membrane proteins. Hunter is tested on the well and partially annotated proteins (2160 and 760, respectively) of Escherichia coli K 12 scoring as high as 95.6% in the correct assignment of each chain to the category. Of the remaining 1253 nonannotated sequences, 1099 are predicted globular, 136 are all‐α, and 18 are all‐β membrane proteins. In Escherichia coli 0157:H7 we filtered 1901 nonannotated proteins. Our analysis classifies 1564 globular chains, 327 inner membrane proteins, and 10 outer membrane proteins. With Hunter, new membrane proteins are added to the list of putative membrane proteins of Gram‐negative bacteria. The content of outer membrane proteins per genome (nine are analyzed) ranges from 1.5% to 2.4%, and it is one order of magnitude lower than that of inner membrane proteins. The finding is particularly relevant when it is considered that this is the first large‐scale analysis based on validated tools that can predict the content of outer membrane proteins in a genome and can allow cross‐comparison of the same protein type between different species.
Reducing the computational complexity of protein folding via fragment folding and assembly
Authors: Haspel Nurit , Tsai Chung‐Jung , Wolfson Haim , Nussinov Ruth
Published: May 2003

Understanding, and ultimately predicting, how a 1‐D protein chain reaches its native 3‐D fold has been one of the most challenging problems during the last few decades. Data increasingly indicate that protein folding is a hierarchical process. Hence, the question arises as to whether we can use the hierarchical concept to reduce the practically intractable computational times. For such a scheme to work, the first step is to cut the protein sequence into fragments that form local minima on the polypeptide chain. The conformations of such fragments in solution are likely to be similar to those when the fragments are embedded in the native fold, although alternate conformations may be favored during the mutual stabilization in the combinatorial assembly process. Two elements are needed for such cutting: (1) a library of (clustered) fragments derived from known protein structures and (2) an assignment algorithm that selects optimal combinations to “cover” the protein sequence. The next two steps in hierarchical folding schemes, not addressed here, are the combinatorial assembly of the fragments and finally, optimization of the obtained conformations. Here, we address the first step in a hierarchical protein‐folding scheme. The input is a target protein sequence and a library of fragments created by clustering building blocks that were generated by cutting all protein structures. The output is a set of cutout fragments. We briefly outline a graph theoretic algorithm that automatically assigns building blocks to the target sequence, and we describe a sample of the results we have obtained.
Analysis of transglutaminase protein substrates by functional proteomics
Authors: Ruoppolo Margherita , Orrù Stefania , D'Amato Alfonsina , Francese Simona , Rovero Paolo , Marino Gennaro , Esposito Carla
Published: May 2003

Transglutaminases are calcium‐dependent enzymes that catalyze a post‐translational modification of proteins through the formation of ε‐(γ‐glutamyl)lysine bonds. Although specific roles for transglutaminases have been described, recent findings have provided evidence that dysregulation of transglutaminases may contribute to many pathological processes including celiac disease and neurodegenerative diseases. A crucial step in the elucidation of biological and pathological roles of transglutaminases requires the identification of protein substrates. A strategy based on a functional proteomic analysis was set up using two well‐characterized biotinylated transglutaminase substrates as affinity probes: 5–(biotinamido)pentylamine and the synthetic biotinylated peptide TVQQEL, the amino‐ and acyl‐donor probes, respectively. A pool of known tissue type transglutaminase protein substrates was selected in order to test the procedure. Results obtained in this paper indicate that the whole strategy can be successfully applied in order to identify transglutaminases protein substrates as well as the amino acid site sensitive toward enzyme activity.
Protein–protein docking with a reduced protein model accounting for side‐chain flexibility
Authors: Zacharias Martin
Published: May 2003

A protein–protein docking approach has been developed based on a reduced protein representation with up to three pseudo atoms per amino acid residue. Docking is performed by energy minimization in rotational and translational degrees of freedom. The reduced protein representation allows an efficient search for docking minima on the protein surfaces within. During docking, an effective energy function between pseudo atoms has been used based on amino acid size and physico‐chemical character. Energy minimization of protein test complexes in the reduced representation results in geometries close to experiment with backbone root mean square deviations (RMSDs) of ∼1 to 3 Å for the mobile protein partner from the experimental geometry. For most test cases, the energy‐minimized experimental structure scores among the top five energy minima in systematic docking studies when using both partners in their bound conformations. To account for side‐chain conformational changes in case of using unbound protein conformations, a multicopy approach has been used to select the most favorable side‐chain conformation during the docking process. The multicopy approach significantly improves the docking performance, using unbound (apo) binding partners without a significant increase in computer time. For most docking test systems using unbound partners, and without accounting for any information about the known binding geometry, a solution within ∼2 to 3.5 Å RMSD of the full mobile partner from the experimental geometry was found among the 40 top‐scoring complexes. The approach could be extended to include protein loop flexibility, and might also be useful for docking of modeled protein structures.
Why is Leu55→Pro55 transthyretin variant the most amyloidogenic: Insights from molecular dynamics simulations of transthyretin monomers
Authors: Yang Mingfeng , Lei Ming , Huo Shuanghong
Published: May 2003

Transthyretin (TTR) is one of the known human amyloidogenic proteins. Its native state is a homotetramer with each monomer having a β‐sandwich structure. Strong experimental evidence suggests that TTR dissociates into monomeric intermediates and that the monomers subsequently self‐assemble to form amyloid deposits and insoluble fibrils. However, details on the early steps along the pathway of TTR amyloid formation are unclear, although various experimental approaches with resolutions at the molecular or residue level have provided some clues. It is highly likely that the stability and flexibility of monomeric TTR play crucial roles in the early steps of amyloid formation; thereby, it is essential to characterize initial conformational changes of TTR monomers. In this article we probe the possibility that the differences in the monomeric forms of wild‐type (WT) TTR and its variants are responsible for differential amyloidogenesis. We begin with the simulations of WT, Val30→Met (V30M), and Leu55→Pro (L55P) TTR monomers. Nanosecond time scale molecular dynamics simulations at 300 K were performed using AMBER. The results indicate that the L55P‐TTR monomer undergoes substantial structural changes relative to fluctuations observed in the WT and V30M TTR monomers. The observation supports earlier speculation that the L55P mutation may lead to disruption of the β‐sheet structure through the disorder of the “edge strands” that might facilitate amyloidogenesis.