bluuebunny/crossref_metadata_2025 huggingface dataset:
Diverse effects of two allosteric inhibitors on the phosphorylation state of glycogen phosphorylase in hepatocytes
Authors: LATSIS Theodore , ANDERSEN Birgitte , AGIUS Loranne
Published: November 2002

Two distinct allosteric inhibitors of glycogen phosphorylase, 1,4-dideoxy-1,4-imino-d-arabinitol (DAB) and CP-91149 (an indole-2-carboxamide), were investigated for their effects on the phosphorylation state of the enzyme in hepatocytes in vitro. CP-91149 induced inactivation (dephosphorylation) of phosphorylase in the absence of hormones and partially counteracted the phosphorylation caused by glucagon. Inhibition of glycogenolysis by CP-91149 can be explained by dephosphorylation of phosphorylase a. This was associated with activation of glycogen synthase and stimulation of glycogen synthesis. DAB, in contrast, induced a small degree of phosphorylation of phosphorylase. This was associated with inactivation of glycogen synthase and inhibition of glycogen synthesis. Despite causing phosphorylation (activation) of phosphorylase, DAB is a very potent inhibitor of glycogenolysis in both the absence and presence of glucagon. This is explained by allosteric inhibition of phosphorylase a, which overrides the increase in activation state. In conclusion, two potent phosphorylase inhibitors exert different effects on glycogen metabolism in intact hepatocytes as a result of opposite effects on the phosphorylation state of both phosphorylase and glycogen synthase.
Up-regulation of c-jun mRNA in cardiac myocytes requires the extracellular signal-regulated kinase cascade, but c-Jun N-terminal kinases are required for efficient up-regulation of c-Jun protein
Authors: CLERK Angela , KEMP Timothy J. , HARRISON Joanne G. , MULLEN Anthony J. , BARTON Paul J.R. , SUGDEN Peter H.
Published: November 2002

Cardiac hypertrophy, an important adaptational response, is associated with up-regulation of the immediate early gene, c-jun, which encodes the c-Jun transcription factor. c-Jun may feed back to up-regulate its own transcription and, since the c-Jun N-terminal kinase (JNK) family of mitogen-activated protein kinases (MAPKs) phosphorylate c-Jun(Ser-63/73) to increase its transactivating activity, JNKs are thought to be the principal factors involved in c-jun up-regulation. Hypertrophy in primary cultures of cardiac myocytes is induced by endothelin-1, phenylephrine or PMA, probably through activation of one or more of the MAPK family. These three agonists increased c-jun mRNA with the rank order of potency of PMAendothelin-1> phenylephrine. Up-regulation of c-jun mRNA by endothelin-1 was attenuated by inhibitors of protein kinase C (GF109203X) and the extracellular signal-regulated kinase (ERK) cascade (PD98059 or U0126), but not by inhibitors of the JNK (SP600125) or p38-MAPK (SB203580) cascades. Hyperosmotic shock (0.5M sorbitol) powerfully activates JNKs, but did not increase c-jun mRNA. These data suggest that ERKs, rather than JNKs, are required for c-jun up-regulation. However, endothelin-1 and phenylephrine induced greater up-regulation of c-Jun protein than PMA and phosphorylation of c-Jun(Ser-63/73) correlated with the level of c-Jun protein. Up-regulation of c-Jun protein by endothelin-1 was attenuated by inhibitors of protein kinase C and the ERK cascade, probably correlating with a primary input of ERKs into transcription. In addition, SP600125 inhibited the phosphorylation of c-Jun(Ser-63/73), attenuated the increase in c-Jun protein induced by endothelin-1 and increased the rate of c-Jun degradation. Thus whereas ERKs are the principal MAPKs required for c-jun transcription, JNKs are necessary to stabilize c-Jun for efficient up-regulation of the protein.
Cytoplasmic interactions of syndecan-4 orchestrate adhesion receptor and growth factor receptor signalling
Authors: BASS Mark D. , HUMPHRIES Martin J.
Published: November 2002

Syndecan-4 is a ubiquitous transmembrane proteoglycan that localizes to the focal adhesions of adherent cells and binds to a range of extracellular ligands, including growth factors and extracellular-matrix proteins. Engagement of syndecan-4 is essential for adhesion formation in cells adhering via certain integrins, and for cell proliferation and migration in response to growth factors. The cytoplasmic domain of syndecan-4 interacts with a number of signalling and structural proteins, and both extracellular and cytoplasmic domains are necessary for regulated activation of associated transmembrane receptors. PDZ domain-containing scaffold proteins (syntenin and CASK) bind to the C-terminus of the syndecan-4 cytoplasmic domain and co-ordinate clustering of receptors and connection to the actin cytoskeleton. Syndecan-4 also binds and activates protein kinase Cα in the presence of phosphatidylinositol 4,5-bisphosphate, and regulates signalling by Rho-family GTPases and focal adhesion kinase. This review discusses the cytoplasmic interactions of syndecan-4 and how they affect cell behaviour as a consequence of the interaction with extracellular ligands. These conclusions also offer an insight into the role of syndecan-4 in vivo, and are consistent with phenotypes generated as a consequence of abnormal syndecan-4 expression in pathologies and gene disruption studies.
Complex adaptive systems: Exploring the known, the unknown and the unknowable
Authors: Levin Simon
Published: November 2002

The study of complex adaptive systems, from cells to societies, is a study of the interplay among processes operating at diverse scales of space, time and organizational complexity. The key to such a study is an understanding of the interrelationships between microscopic processes and macroscopic patterns, and the evolutionary forces that shape systems. In particular, for ecosystems and socioeconomic systems, much interest is focused on broad scale features such as diversity and resiliency, while evolution operates most powerfully at the level of individual agents. Understanding the evolution and development of complex adaptive systems thus involves understanding how cooperation, coalitions and networks of interaction emerge from individual behaviors and feed back to influence those behaviors. In this paper, some of the mathematical challenges are discussed.
Recent progress in algebraic combinatorics
Authors: Stanley Richard
Published: November 2002

We survey three recent breakthroughs in algebraic combinatorics. The first is the proof by Knutson and Tao, and later Derksen and Weyman, of the saturation conjecture for Littlewood-Richardson coefficients. The second is the proof of then!n!and(n+1)n−1(n+1)^{n-1}conjectures by Haiman. The final breakthrough is the determination by Baik, Deift, and Johansson of the limiting behavior of the length of the longest increasing subsequence of a random permutation.
Some mathematical challenges in materials science
Authors: Taylor Jean
Published: November 2002

Four challenges to mathematics research posed by the field of materials science are given, plus an additional challenge purely from the field of geometric measure theory. The problems all concern the effects of surface and grain boundary free energy: motion by weighted mean curvature and/or surface diffusion and/or other kinetics, proofs of minimality of soap bubble clusters and their anisotropic analogs, shapes of crystals in a gravitational or other field, incorporating data from simulations into mathematics, and understanding flat chains modulo

ν
\nu

. The figures are selected copies of transparencies presented at the lecture on which this paper is based.
ARROGANT: an application to manipulate large gene collections
Authors: Kulkarni Amit V. , Williams Noelle Sevilir , Lian Yun , Wren Jonathan D. , Mittelman David , Pertsemlidis Alexander , Garner Harold R.
Published: November 2002

Summary: ARROGANT (ARRay OrGANizing Tool) is a software tool developed to facilitate the identification, annotation and comparison of large collections of genes or clones. The objective is to enable users to compile gene/clone collections from different databases, allowing them to design experiments and analyze the collections as well as associated experimental data efficiently. ARROGANT can relate different sequence identifiers to their common reference sequence using the UniGene database, allowing for the comparison of data from two different microarray experiments. ARROGANT has been successfully used to analyze microarray expression data for colon cancer, to compile genes potentially related to cardiac diseases for subsequent resequencing (to identify single nucleotide polymorphisms, SNPs), to design a new comprehensive human cDNA microarray for cancer, to combine and compare expression data generated by different microarrays and to provide annotation for genes on custom and Affymetrix chips.

Availability: ARROGANT is freely available for use on the web at http://lethargy.swmed.edu/

Contact: harold.garner@utsouthwestern.edu

* To whom correspondence should be addressed.
Identification of mixups among DNA sequencing plates
Authors: Stojanovic Nikola , Chang Jean L. , Lehoczky Jessica , Zody Michael C. , Dewar Ken
Published: November 2002

Motivation: During the process of high-throughput genome sequencing there are opportunities for mixups of reagents and data associated with particular projects. The sequencing templates or sequence data generated for an assembly may become contaminated with reagents or sequences from another project, resulting in poorer quality and inaccurate assemblies.

Results: We have developed a system to assess sequence assemblies and monitor for laboratory mixups. We describe several methods for testing the consistency of assemblies and resolving mixed ones. We use statistical tests to evaluate the distribution of sequencing reads from different plates into contigs, and a graph-based approach to resolve situations where data has been inappropriately combined. While these methods have been designed for use in a high-throughput DNA sequencing environment processing thousands of clones, they can be applied in any situation where distinct sequencing projects are performed at redundant coverage.

Availability: Our software is available for downloading from: ftp-genome.wi.mit.edu/distribution/mixups_detection

Contact: nick@genome.wi.mit.edu

* To whom correspondence should be addressed.
Comparison of microarray designs for class comparison and
class discovery
Authors: Dobbin K. , Simon R.
Published: November 2002

Motivation: Two-color microarray experiments in which an aliquot derived from a common RNA sample is placed on each array are called reference designs. Traditionally, microarray experiments have used reference designs, but designs without a reference have recently been proposed as alternatives.

Results: We develop a statistical model that distinguishes the different levels of variation typically present in cancer data, including biological variation among RNA samples, experimental error and variation attributable to phenotype. Within the context of this model, we examine the reference design and two designs which do not use a reference, the balanced block design and the loop design, focusing particularly on efficiency of estimates and the performance of cluster analysis. We calculate the relative efficiency of designs when there are a fixed number of arrays available, and when there are a fixed number of samples available. Monte Carlo simulation is used to compare the designs when the objective is class discovery based on cluster analysis of the samples. The number of discrepancies between the estimated clusters and the true clusters were significantly smaller for the reference design than for the loop design. The efficiency of the reference design relative to the loop and block designs depends on the relation between inter- and intra-sample variance. These results suggest that if cluster analysis is a major goal of the experiment, then a reference design is preferable. If identification of differentially expressed genes is the main concern, then design selection may involve a consideration of several factors.

Contact: dobbinke@mail.nih.gov

Supplementary Information: Supplementary material referenced in the text can be found at http://linus.nci.nih.gov/~brb/TechReport.htm

* To whom correspondence should be addressed.
Gene expression data analysis with a dynamically extended
self-organized map that exploits class information
Authors: Mavroudi Seferina , Papadimitriou Stergios , Bezerianos Anastasios
Published: November 2002

Motivation: Currently the most popular approach to analyze genome-wide expression data is clustering. One of the major drawbacks of most of the existing clustering methods is that the number of clusters has to be specified a priori. Furthermore, by using pure unsupervised algorithms prior biological knowledge is totally ignored Moreover, most current tools lack an effective framework for tight integration of unsupervised and supervised learning for the analysis of high-dimensional expression data and only very few multi-class supervised approaches are designed with the provision for effectively utilizing multiple functional class labeling.

Results: The paper adapts a novel Self-Organizing map called supervised Network Self-Organized Map (sNet-SOM) to the peculiarities of multi-labeled gene expression data. The sNet-SOM determines adaptively the number of clusters with a dynamic extension process. This process is driven by an inhomogeneous measure that tries to balance unsupervised, supervised and model complexity criteria. Nodes within a rectangular grid are grown at the boundary nodes, weights rippled from the internal nodes towards the outer nodes of the grid, and whole columns inserted within the map The appropriate level of expansion is determined automatically. Multiple sNet-SOM models are constructed dynamically each for a different unsupervised/supervised balance and model selection criteria are used to select the one optimum one. The results indicate that sNet-SOM yields competitive performance to other recently proposed approaches for supervised classification at a significantly reduced computational cost and it provides extensive exploratory analysis potentiality within the analysis framework. Furthermore, it explores simple design decisions that are easier to comprehend and computationally efficient.

Availability: The source code of the algorithms presented in the paper can be downloaded from http://heart.med.upatras.gr. The implementation is in Borland C++ Builder 5.0.

Contact: severina@heart.med.upatras.gr

* To whom correspondence should be addressed.
Methods for assessing reproducibility of clustering patterns observed in analyses of microarray data
Authors: McShane Lisa M. , Radmacher Michael D. , Freidlin Boris , Yu Ren , Li Ming-Chung , Simon Richard
Published: November 2002

Motivation: Recent technological advances such as cDNA microarray technology have made it possible to simultaneously interrogate thousands of genes in a biological specimen. A cDNA microarray experiment produces a gene expression ‘profile’. Often interest lies in discovering novel subgroupings, or ‘clusters’, of specimens based on their profiles, for example identification of new tumor taxonomies. Cluster analysis techniques such as hierarchical clustering and self-organizing maps have frequently been used for investigating structure in microarray data. However, clustering algorithms always detect clusters, even on random data, and it is easy to misinterpret the results without some objective measure of the reproducibility of the clusters.

Results: We present statistical methods for testing for overall clustering of gene expression profiles, and we define easily interpretable measures of cluster-specific reproducibility that facilitate understanding of the clustering structure. We apply these methods to elucidate structure in cDNA microarray gene expression profiles obtained on melanoma tumors and on prostate specimens.

Availability: Software to implement these methods is contained in BRB ArrayTools microarray analysis package available from http://linus.nci.nih.gov./BRB-ArrayTools.html

Contact: lm5h@nih.gov

* To whom correspondence should be addressed.

† Present address: Human Genome Sciences Inc., Rockville, MD 20850, USA
Theoretical and experimental comparisons of gene
expression indexes for oligonucleotide arrays
Authors: Lemon William J. , Palatini Jeffrey J.T. , Krahe Ralf , Wright Fred A.
Published: November 2002

Motivation: Oligonucleotide expression arrays exhibit systematic and reproducible variation produced by the multiple distinct probes used to represent a gene. Recently, a gene expression index has been proposed that explicitly models probe effects, and provides improved fits of hybridization intensity for arrays containing perfect match (PM) and mismatch (MM) probe pairs.

Results: Here we use a combination of analytical arguments and empirical data to show directly that the estimates provided by model-based expression indexes are superior to those provided by commercial software. The improvement is greatest for genes in which probe effects vary substantially, and modeling the PM and MM intensities separately is superior to using the PM–MM differences. To empirically compare expression indexes, we designed a mixing experiment involving three groups of human fibroblast cells (serum starved, serum stimulated, and a 50:50 mixture of starved/stimulated), with six replicate HuGeneFL arrays in each group. Careful spiking of control genes provides evidence that 88–98% of the genes on the array are detectably transcribed, and that the model-based estimates can accurately detect the presence versus absence of a gene. The use of extensive replication from single RNA sources enables exploration of the technical variability of the array.

Availability: Scripts for computing the Li–Wong reduced and full models are available in C, Splus and Perl in the supplementary information.

Contact: fwright@bios.unc.edu

Supplementary information: http://thinker.med.ohio-state.edu

* To whom correspondence should be addressed at Present address: Department of Biostatistics UNC-CH, 3107B McGavran-Greenberg Hall, CB #7420, Chapel Hill, NC 27599-7420, USA
Statistical analysis of a small set of time-ordered gene
expression data using linear splines
Authors: de Hoon M.J.L. , Imoto S. , Miyano S.
Published: November 2002

Motivation: Recently, the temporal response of genes to changes in their environment has been investigated using cDNA microarray technology by measuring the gene expression levels at a small number of time points. Conventional techniques for time series analysis are not suitable for such a short series of time-ordered data. The analysis of gene expression data has therefore usually been limited to a fold-change analysis, instead of a systematic statistical approach.

Methods: We use the maximum likelihood method together with Akaike's Information Criterion to fit linear splines to a small set of time-ordered gene expression data in order to infer statistically meaningful information from the measurements. The significance of measured gene expression data is assessed using Student's t-test.

Results: Previous gene expression measurements of the cyanobacterium Synechocystis sp. PCC6803 were reanalyzed using linear splines. The temporal response was identified of many genes that had been missed by a fold-change analysis. Based on our statistical analysis, we found that about four gene expression measurements or more are needed at each time point.

Availability: An extension module for Python to calculate linear spline functions is available at http://bonsai.ims.u-tokyo.ac.jp/~mdehoon. This software package (with patent pending) is free of charge for academic use only.

Contact: mdehoon@ims.u-tokyo.ac.jp

* To whom correspondence should be addressed.
A duplication growth model of gene expression networks
Authors: Bhan Ashish , Galas David J. , Dewey T. Gregory
Published: November 2002

Motivation: There has been considerable interest in developing computational techniques for inferring genetic regulatory networks from whole-genome expression profiles. When expression time series data sets are available, dynamic models can, in principle, be used to infer correlative relationships between gene expression levels, which may be causal. However, because of the range of detectable expression levels and the current quality of the data, the predictive nature of such inferred, quantitative models is questionable. Network models derived from simple rate laws offer an intermediate level analysis, going beyond simple statistical analysis, but falling short of a fully quantitative description. This work shows how such network models can be constructed and describes the global properties of the networks derived from such a model. These global properties are statistically robust and provide insights into the design of the underlying network.

Results: Several whole-genome expression time series data sets from yeast microarray experiments were analyzed using a Markov-modeling method (Dewey and Galas, Func. Integr. Genomics, 1, 269–278, 2001) to infer an approximation to the underlying genetic network. We found that the global statistical properties of all the resulting networks are similar. The overall structure of these biological networks is distinctly different from that of other recently studied networks such as the Internet or social networks. These biological networks show hierarchical, hub-like structures that have some properties similar to a class of graphs known as small world graphs. Small world networks exhibit local cliquishness while exhibiting strong global connectivity. In addition to the small world properties, the biological networks show a power law or scale free distribution of connectivities. An inverse power law, N(k)∼k-3/2, for the number of vertices (genes) with k connections was observed for three different data sets from yeast. We propose network growth models based on gene duplication events. Simulations of these models yield networks with the same combination of global graphical properties that we inferred from the expression data.

Contact: Ashish_Bhan@kgi.eduDavid_Galas@kgi.eduGreg_Dewey@kgi.edu

Supplementary Information: http://www.kgi.edu/html/noncore/faculty/dewey/bioinf.pdf

* To whom correspondence should be addressed.
A simulated annealing algorithm for finding consensus sequences
Authors: Keith Jonathan M. , Adams Peter , Bryant Darryn , Kroese Dirk P. , Mitchelson Keith R. , Cochran Duncan A.E. , Lala Gita H.
Published: November 2002

Motivation: A consensus sequence for a family of related sequences is, as the name suggests, a sequence that captures the features common to most members of the family. Consensus sequences are important in various DNA sequencing applications and are a convenient way to characterize a family of molecules.

Results: This paper describes a new algorithm for finding a consensus sequence, using the popular optimization method known as simulated annealing. Unlike the conventional approach of finding a consensus sequence by first forming a multiple sequence alignment, this algorithm searches for a sequence that minimises the sum of pairwise distances to each of the input sequences. The resulting consensus sequence can then be used to induce a multiple sequence alignment. The time required by the algorithm scales linearly with the number of input sequences and quadratically with the length of the consensus sequence. We present results demonstrating the high quality of the consensus sequences and alignments produced by the new algorithm. For comparison, we also present similar results obtained using ClustalW. The new algorithm outperforms ClustalW in many cases.

Availability: The software is made available upon request.

Contact: jonathan@maths.uq.edu.au.

* To whom correspondence should be addressed.
Empirical determination of effective gap penalties for sequence comparison
Authors: Reese J.T. , Pearson W.R.
Published: November 2002

Motivation: No general theory guides the selection of gap penalties for local sequence alignment. We empirically determined the most effective gap penalties for protein sequence similarity searches with substitution matrices over a range of target evolutionary distances from 20 to 200 Point Accepted Mutations (PAMs).

Results: We embedded real and simulated homologs of protein sequences into a database and searched the database to determine the gap penalties that produced the best statistical significance for the distant homologs. The most effective penalty for the first residue in a gap (q+r) changes as a function of evolutionary distance, while the gap extension penalty for additional residues (r) does not. For these data, the optimal gap penalties for a given matrix scaled in 1/3 bit units (e.g. BLOSUM50, PAM200) are q=25−0.1 • (target PAM distance), r=5. Our results provide an empirical basis for selection of gap penalties and demonstrate how optimal gap penalties behave as a function of the target evolutionary distance of the substitution matrix. These gap penalties can improve expectation values by at least one order of magnitude when searching with short sequences, and improve the alignment of proteins containing short sequences repeated in tandem.

Contact: wrp@virginia.edu

* To whom correspondence should be addressed.
Finding relevant references to genes and proteins in Medline
using a Bayesian approach
Authors: Leonard Julie E. , Colombe Jeffrey B. , Levy Joshua L.
Published: November 2002

Motivation: Mining the biomedical literature for references to genes and proteins always involves a tradeoff between high precision with false negatives, and high recall with false positives. Having a reliable method for assessing the relevance of literature mining results is crucial to finding ways to balance precision and recall, and for subsequently building automated systems to analyze these results. We hypothesize that abstracts and titles that discuss the same gene or protein use similar words. To validate this hypothesis, we built a dictionary- and rule-based system to mine Medline for references to genes and proteins, and used a Bayesian metric for scoring the relevance of each reference assignment.

Results: We analyzed the entire set of Medline records from 1966 to late 2001, and scored each gene and protein reference using a Bayesian estimated probability (EP) based on word frequency in a training set of 137837 known assignments from 30594 articles to 36197 gene and protein symbols. Two test sets of 148 and 150 randomly chosen assignments, respectively, were hand-validated and categorized as either good or bad. The distributions of EP values, when plotted on a log-scale histogram, are shown to markedly differ between good and bad assignments. Using EP values, recall was 100% at 61% precision (EP=2×10−5), 63% at 88% precision (EP=0.008), and 10% at 100% precision (EP=0.1). These results show that Medline entries discussing the same gene or protein have similar word usage, and that our method of assessing this similarity using EP values is valid, and enables an EP cutoff value to be determined that accurately and reproducibly balances precision and recall, allowing automated analysis of literature mining results.

Contact: jlevy@incellico.com; jleonard@incellico.com; jeffcolombe@hotmail.com.

* To whom correspondence should be addressed.
AcePrimer: automation of PCR primer design based on gene
structure
Authors: McKay Sheldon J. , Jones Steven J.M.
Published: November 2002

Summary: AcePrimer is an internet-accessed application based on CGI/Perl programming that designs PCR primers to search for deletion alleles in Caenorhabditis elegans gene knockout experiments and uses electronic PCR to search the entire genomic DNA sequence for potential false priming or multiple PCR amplification targets. Features such as the ability to target specific exons with the ‘poison primer’ approach and evaluation of primers with electronic PCR provide a flexible, web-based approach to design effective primers whilst minimizing the need for empirical optimization of PCR experiments.

Availability: Web access to this program is provided at http://elegans.bcgsc.bc.ca/gko/aceprimer.shtml.

* To whom correspondence should be addressed.
SNOMAD (Standardization and NOrmalization of MicroArray
Data): web-accessible gene expression data analysis
Authors: Colantuoni Carlo , Henry George , Zeger Scott , Pevsner Jonathan
Published: November 2002

Summary: SNOMAD is a collection of algorithms for the normalization and standardization of gene expression datasets derived from diverse biological and technological sources. In addition to conventional transformations and visualization tools, SNOMAD includes two non-linear transformations which correct for bias and variance which are non-uniformly distributed across the range of microarray element signal intensities: (1) Local mean normalization; and (2) Local variance correction (Z-score generation using a locally calculated standard deviation).

Availability: The SNOMAD tools were developed in the R statistical language http://www.r-project.org/. SNOMAD is an interactive, user-friendly web-application which can be accessed freely via the internet with any standard HTML browser: http://pevsnerlab.kennedykrieger.org/snomad.htm.

Contact: ccolantu@jhmi.edu or pevsner@jhmi.edu

* To whom correspondence should be addressed.

† Present address: Wadham College, Oxford University, UK.
GeneCards™ 2002: towards a complete, object-oriented, human gene compendium
Authors: Safran Marilyn , Solomon Irina , Shmueli Orit , Lapidot Michal , Shen-Orr Shai , Adato Avital , Ben-Dor Uri , Esterman Nir , Rosen Naomi , Peter Inga , Olender Tsviya , Chalifa-Caspi Vered , Lancet Doron
Published: November 2002

Motivation: In the post-genomic era, functional analysis of genes requires a sophisticated interdisciplinary arsenal. Comprehensive resources are challenged to provide consistently improving, state-of-the-art tools.

Results: GeneCards (Rebhan et al., 1998) has made innovative strides: (a) regular updates and enhancements incorporating new genes enriched with sequences, genomic locations, cDNA assemblies, orthologies, medical information, 3D protein structures, gene expression, and focused SNP summaries; (b) restructured software using object-oriented Perl, migration to schema-driven XML, and (c) pilot studies, introducing methods to produce cards for novel and predicted genes.

Availability: Freely available for educational and research purposes by non-profit institutions at http://bioinfo.weizmann.ac.il/cards and academic mirror sites. Commercial usage requires a license.

Contact: marilyn.safran@weizmann.ac.il

Supplementary Information: http://bioinfo.weizmann.ac.il/cards/9pageGC2002Bioinformatics.doc; http://bioinfo.weizmann.ac.il/cards/GeneCardByResource.xsd and http://bioinfo.weizmann.ac.il/cards/GeneCardByFunction.xsd.

* To whom correspondence should be addressed.
QuickTree: building huge Neighbour-Joining trees of
protein sequences
Authors: Howe Kevin , Bateman Alex , Durbin Richard
Published: November 2002

Summary: We have written a fast implementation of the popular Neighbor-Joining tree building algorithm. QuickTree allows the reconstruction of phylogenies for very large protein families (including the largest Pfam alignment containing 27000 HIV GP120 glycoprotein sequences) that would be infeasible using other popular methods.

Availability: The source-code for QuickTree, written in ANSI~C, is freely available via the world wide web at http://www.sanger.ac.uk/Software/analysis/quicktree

Contact: klh@sanger.ac.uk

* To whom correspondence should be addressed.
Ramachandran plot on the web
Authors: Sheik S.S. , Sundararajan P. , Hussain A.S.Z. , Sekar K.
Published: November 2002

Summary: A graphics package has been developed to display the main chain torsion angles phi, psi (φ, Ψ); (Ramachandran angles) in a protein of known structure. In addition, the package calculates the Ramachandran angles at the central residue in the stretch of three amino acids having specified the flanking residue types. The package displays the Ramachandran angles along with a detailed analysis output. This software is incorporated with all the protein structures available in the Protein Databank.

Availability: This package is available over the world wide web at http://144.16.71.146/rp/ or http://dicsoft1.physics.iisc.ernet.in/rp.

Contact: sekar@physics.iisc.ernet.in

* To whom correspondence should be addressed.

† This work is dedicated to Late Professor G. N. Ramachandran.
Digital visibility: menu prominence and its impact on use. Case study: the NHS Direct Digital channel on Kingston Interactive Television
Authors: Nicholas David , Huntington Paul , Williams Peter , Gunter Barrie
Published: November 2002

During an evaluation of a digital interactive consumer health television channel (NHS Direct) on Kingston Interactive Television the prominence of the channel’s menus regarding the interactive element of its service diminished considerably over a period of four months. During this time the use of the channel declined significantly, a development that can be attributed, at least in part, to the reduction in visibility of the channel. A number of metrics (users, return visits, screens viewed, screens viewed during a visit, and time spent viewing) were employed to chart and explain the decline. Two changes to the positioning of the channel resulted in a drop of about one‐third in the number of users. Other metrics – page views and return visitors – saw similar declines.
The Internet as an information conduit in developing countries: an investigation of World Wide Web usability among small and medium textile enterprises in Botswana
Authors: Mbambo Buhle , Cronjé Johannes C.
Published: November 2002

The Internet has been called the technology of the century because it is expected to reduce the development gap between developing countries and developed ones. This article examines the validity of that assertion. The researcher examines Internet use at two levels. The first level is the macrolevel of issues of Internet connectivity in developing countries and the second level is the microlevel of the usability of the World Wide Web (WWW) for information management in a developing country, Botswana. The two research methodologies of content analysis and case study were used for this study. The findings of this study are that entrepreneurs found a Website easy to use, but while there is a need for macropolicy to create national and global environments for using the Internet sustainable connection should not be universal, but should rather be based on the information management needs of a target population. Inherent infrastructural and socio‐technical challenges should then be tackled as part of the effort to create a sustainable Internet usage.
Innovative pricing effects: theory and practice in mobile Internet networks
Authors: Jonason Andreas
Published: November 2002

Multidimensional products, such as telecommunications, often distinguish themselves by a considerable number of spillovers. The creator of the spillovers wants to commercialize the spillovers but cannot if the parameters on which the ability to charge is proprietary to another firm in the economy. These actors then need to agree upon an efficient pricing contract to be able to charge. As an effect, the direction of revenue in the transaction may not be self‐evident, turning previous customers into suppliers and vice versa. The paper presents data from the mobile Internet market to validate this claim empirically and make suggestions of possible solutions to the pricing problem facing these actors with the introduction of mobile multimedia.
New product development in German and US technology firms
Authors: Simpson James T. , Kollmannsberger Christine , Schmalen Helmut , Berkowitz David
Published: November 2002

This research tested a model in both Germany and the USA that contained marketing variables known to impact new product development success in high technology firms. We explore the link between national culture and new product development. A multi‐group LISREL analysis revealed that while the model structure is valid for both countries, the impact of certain marketing factors on commercial product success differed. The analysis revealed that the mean values of the marketing factors differed significantly in each country. The most important determinant of new product success in both countries is proficiency in product launch activities. Marketing skills also positively impact product success in both countries. Top management support and involvement was also an important predictor of new product success in Germany, but the impact was negative. The potential impact of culture on the findings is discussed.
Formalization and innovation revisited
Authors: Bodewes Wynand E.J.
Published: November 2002

The many studies into the relationships between formalization and innovation have produced little but inconsistent findings. The conceptual and operational definition of the formalization construct is proposed to be one of the reasons for these inconsistencies. It is argued that aggregate (organization‐level) measurements of formalization are inappropriate and should be replaced with department‐specific or process‐specific measurements. Second, it is argued that formalization has been defined in an inconsistent way. However, it is not just the coexistence of different definitions (and their measurements) that is problematic. The exclusion, or improper inclusion, of rule observation from the conceptualization of formalization appears to be a third fallacy. A revised definition of formalization is advanced as a solution to these problems. This definition may prove to be instrumental in determining the true effect of formalization on organizational innovation.
Open or closed strategy in developing new products? A case study of industrial NPD in SMEs
Authors: Tapio Lindman Martti
Published: November 2002

This case study reports the quality of industrial new product development in five small‐ to medium‐sized enterprises (SMEs) in the Finnish metal industry. The findings indicate that SMEs tend to lack a long run perspective; that the role of new products in business strategy calls for clarity and that the whole goal setting as to future new product efforts is limited. The fit between market requirements and firms’ own resources is managed due to the flexibility SMEs have and by relying on an in‐house knowledge base generated through a close understanding of user conditions. In this respect SMEs are apt to rely on reactive and closed new product strategies only. Even if successful in the past, such strategies risk being unable to identify and take advantage of any business opportunities outside the present product scope. Also, the increasing need of networking may turn out a threat if SMEs cannot establish more open development strategies.
Reactivation of Ocular Dominance Plasticity in the Adult Visual Cortex
Authors: Pizzorusso Tommaso , Medini Paolo , Berardi Nicoletta , Chierzi Sabrina , Fawcett James W. , Maffei Lamberto
Published: November 2002

In young animals, monocular deprivation leads to an ocular dominance shift, whereas in adults after the critical period there is no such shift. Chondroitin sulphate proteoglycans (CSPGs) are components of the extracellular matrix (ECM) inhibitory for axonal sprouting. We tested whether the developmental maturation of the ECM is inhibitory for experience-dependent plasticity in the visual cortex. The organization of CSPGs into perineuronal nets coincided with the end of the critical period and was delayed by dark rearing. After CSPG degradation with chondroitinase-ABC in adult rats, monocular deprivation caused an ocular dominance shift toward the nondeprived eye. The mature ECM is thus inhibitory for experience-dependent plasticity, and degradation of CSPGs reactivates cortical plasticity.
Spatial and Temporal Offsets Between Proxy Records in a Sediment Drift
Authors: Ohkouchi Nao , Eglinton Timothy I. , Keigwin Lloyd D. , Hayes John M.
Published: November 2002

Chronologies for Late Quaternary marine sediment records are usually based on radiocarbon ages of planktonic foraminifera. Signals carried by other sedimentary components measured in parallel can provide complementary paleoclimate information. A key premise is that microfossils and other indicators within a given sediment horizon are of equal age. We show here that haptophyte-derived alkenones isolated from Bermuda Rise drift sediments are up to 7000 years older than coexisting planktonic foraminifera. This temporal offset, which is apparently due to lateral transport of alkenones on fine-grained particles from the Nova Scotian margin, markedly influences molecular estimates of sea surface temperatures. More broadly, the observation raises questions about both the temporal and the geographic fidelity of paleoenvironmental records encoded by readily transported components of sediments.
Avian Persistence in Fragmented Rainforest
Authors: Lens Luc , Van Dongen Stefan , Norris Ken , Githiru Mwangi , Matthysen Erik
Published: November 2002

What factors determine the persistence of species in fragmented habitats? To address this question, we studied the relative impacts of forest deterioration and fragmentation on bird species in 12 rainforest fragments in Kenya, combining 6 years of individual capture-recapture data with measurements of current captures and museum specimens. Species mobility, as estimated from species-specific dispersal rates, and tolerance to habitat deterioration, as estimated from change in fluctuating asymmetry with increasing habitat disturbance, explained 88% of the variation in patch occupancy among eight forest bird species. Occupancy increased with mobility and with tolerance to deterioration, where both variables contributed equally to this relationship. We conclude that individual-level study, such as of dispersal behavior and phenotypic development, can predict patterns of persistence at the species level. More generally, for conservation tactics to stand a high chance of success, they should include action both within sites, to minimize habitat deterioration, and across landscapes, to maximize dispersal.
Fossil Echinoderms As Monitor of the Mg/Ca Ratio of Phanerozoic Oceans
Authors: Dickson J. A. D.
Published: November 2002

Opinion has long been divided as to whether the Mg/Ca ratio of seawater remained constant during the Phanerozoic or underwent substantial secular change. Existing empirical evidence for the Mg/Ca of ancient seawater provides a poorly resolved and often controversial signal. Echinoderm fossils that have retained their bulk original chemistry, despite micrometer-scale changes, preserve a record of seawater Mg/Ca and confirm that major changes in Mg/Ca occurred during the Phanerozoic. Echinoderms from the Cambrian and from the Carboniferous to the Triassic indicate a seawater Mg/Ca of ∼3.3, whereas echinoderms from the Jurassic to the Cretaceous indicate a Mg/Ca of ∼1.4. The present seawater Mg/Ca is ∼5.
Emotion, Cognition, and Behavior
Authors: Dolan R. J.
Published: November 2002

Emotion is central to the quality and range of everyday human experience. The neurobiological substrates of human emotion are now attracting increasing interest within the neurosciences motivated, to a considerable extent, by advances in functional neuroimaging techniques. An emerging theme is the question of how emotion interacts with and influences other domains of cognition, in particular attention, memory, and reasoning. The psychological consequences and mechanisms underlying the emotional modulation of cognition provide the focus of this article.
The Neurotrophin Receptor p75
NTR
as a Positive Modulator of Myelination
Authors: Cosgaya José M. , Chan Jonah R. , Shooter Eric M.
Published: November 2002

Schwann cells in developing and regenerating peripheral nerves express elevated levels of the neurotrophin receptor p75
NTR
. Neurotrophins are key mediators of peripheral nervous system myelination. Our results show that myelin formation is inhibited in the absence of functional p75
NTR
and enhanced by blocking TrkC activity. Moreover, the enhancement of myelin formation by endogenous brain-derived neurotrophic factor is mediated by the p75
NTR
receptor, whereas TrkC receptors are responsible for neurotrophin-3 inhibition. Thus p75
NTR
and TrkC receptors have opposite effects on myelination.
Risks and Profits
Authors: Rosenberg Charles E.
Published: November 2002

Deceit and Denial
. The Deadly Politics of Industrial Pollution. Gerald Markowitz and David Rosner. University of California Press, Berkeley, and Milbank Memorial Fund, New York, 2002. 428 pp. $34.95, £24.95. ISBN 0-520-21749-7.

The authors, historians whose work has long focused on issue of occupational disease, describe the efforts of the chemical and lead industries to hide the dangers of their products to workers, consumers, and the public.
Lucifer in the Sky with Dinosaurs
Authors: Triunfol Marcia L.
Published: November 2002

The Prophet and the Astronomer
. A Scientific Journey to the End of Time. Marcelo Gleiser. Norton, New York, 2002. 272 pp. $26.95, C$38.99. ISBN 0-393-04987-6.

In this account of cosmology for the nonspecialist, Gleiser focuses on apocalyptic ideas in science and religion and on the scientific inspiration humans have drawn from their spiritual yearnings.
Vibrational Transition Moment Angles in Isolated Biomolecules: A Structural Tool
Authors: Dong F. , Miller R. E.
Published: November 2002

Infrared spectroscopy is used extensively in the study of isolated biomolecules, but it becomes less useful as it is applied to systems of increasing complexity. Even if the individual vibrational bands can be resolved spectroscopically, their assignment becomes problematic when they are more closely spaced than can be determined using ab initio methods. We describe a method that helps to alleviate this difficulty by measuring the direction of the vibrational transition moment for each vibrational band. The molecules of interest (adenine and cytosine) are cooled to 0.37 kelvin in liquid helium nanodroplets and oriented in a large dc electric field. A polarized infrared laser is then used to determine the directions of the infrared transition moments relative to the permanent dipole moment. Comparisons with ab initio calculations provide detailed structural information, including experimental evidence for nonplanarity of adenine and three tautomers of cytosine.
Gender and Science in the DNA Story
Authors: Fausto-Sterling Anne
Published: November 2002

Rosalind Franklin
. Dark Lady of DNA. Brenda Maddox. HarperCollins, London and New York, 2002. 400 pp. £20. ISBN 0-00-257149-8. $29.95, C$44.95. ISBN 0-06-018407-8.

Maddox provides a detailed and nu-anced biography of the researcher whose x-ray diffraction photograph of DNA was crucial to the determination of the mole-cule's structure.
Superconductivity in Dense Lithium
Authors: Struzhkin Viktor V. , Eremets Mikhail I. , Gan Wei , Mao Ho-kwang , Hemley Russell J.
Published: November 2002

Superconductivity in compressed lithium is observed by magnetic susceptibility and electrical resistivity measurements. A superconducting critical temperature (
T
c
) is found ranging from 9 to 16 kelvin at 23 to 80 gigapascals. The pressure dependence of
T
c
suggests multiple phase transitions, consistent with theoretical predictions and reported x-ray diffraction results. The observed values for
T
c
are much lower than those theoretically predicted, indicating that more sophisticated theoretical treatments similar to those proposed for metallic hydrogen may be required to understand superconductivity in dense phases of lithium.