bluuebunny/crossref_metadata_2025 huggingface dataset:
A simple algorithm to infer gene duplication and speciation
events on a gene tree
Authors: Zmasek Christian M. , Eddy Sean R.
Published: September 2002

Motivation: When analyzing protein sequences using sequence similarity searches, orthologous sequences (that diverged by speciation) are more reliable predictors of a new protein’s function than paralogous sequences (that diverged by gene duplication), because duplication enables functional diversification. The utility of phylogenetic information in high-throughput genome annotation (‘phylogenomics’) is widely recognized, but existing approaches are either manual or indirect (e.g. not based on phylogenetic trees). Our goal is to automate phylogenomics using explicit phylogenetic inference. A necessary component is an algorithm to infer speciation and duplication events in a given gene tree.

Results: We give an algorithm to infer speciation and duplication events on a gene tree by comparison to a trusted species tree. This algorithm has a worst-case running time of O(\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(n^{2}\) \end{document}) which is inferior to two previous algorithms that are \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \({\sim}\) \end{document}O(\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(n\) \end{document}) for a gene tree of \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(n\) \end{document}sequences. However, our algorithm is extremely simple, and its asymptotic worst case behavior is only realized on pathological data sets. We show empirically, using 1750 gene trees constructed from the Pfam protein family database, that it appears to be a practical (and often superior) algorithm for analyzing real gene trees.

Availability: http://www.genetics.wustl.edu/eddy/forester

Contact: zmasek@genetics.wustl.edu; eddy@genetics.wustl.edu
Knowledge representation of signal transduction pathways
Authors: Fukuda Ken-ichiro , Takagi Toshihisa
Published: September 2002

Motivations: Signal transduction is the common term used to define a diverse topic that encompasses a large body of knowledge about the biochemical mechanisms. Since most of the knowledge of signal transduction resides in scientific articles and is represented by texts in natural language or by diagrams, there is the need of a knowledge representation model for signal transduction pathways that can be as readily processed by a computer as it is easily understood by humans.

Results: A signal transduction pathway representation model is presented. It is based on a compound graph structure and is designed to handle the diversity and hierarchical structure of pathways. A prototype knowledge base was implemented on a deductive database and a number of biological queries are demonstrated on it.

Contact: fukuda-cbrc@aist.go.jp; ichiro@ims.u-tokyo.ac.jp

2 Present address: Computational Biology Research Center (CBRC), NationalInstitute of Advanced Industrial Science and Technology (AIST) 2-41-6 Aomi, Koutou-ku, Tokyo 135-0064, Japan.
GeneMachine: gene prediction and sequence annotation
Authors: Makalowska Izabela , Ryan Joseph F. , Baxevanis Andreas D.
Published: September 2002

Motivation: A number of free-standing programs have been developed in order to help researchers find potential coding regions and deduce gene structure for long stretches of what is essentially ‘anonymous DNA’. As these programs apply inherently different criteria to the question of what is and is not a coding region, multiple algorithms should be used in the course of positional cloning and positional candidate projects to assure that all potential coding regions within a previously-identified critical region are identified.

Results: We have developed a gene identification tool called GeneMachine which allows users to query multiple exon and gene prediction programs in an automated fashion. BLAST searches are also performed in order to see whether a previously-characterized coding region corresponds to a region in the query sequence. A suite of Perl programs and modules are used to run MZEF, GENSCAN, GRAIL 2, FGENES, RepeatMasker, Sputnik, and BLAST. The results of these runs are then parsed and written into ASN.1 format. Output files can be opened using NCBI Sequin, in essence using Sequin as both a workbench and as a graphical viewer. The main feature of GeneMachine is that the process is fully automated; the user is only required to launch GeneMachine and then open the resulting file with Sequin. Annotations can then be made to these results prior to submission to GenBank, thereby increasing the intrinsic value of these data.

Availability: GeneMachine is freely-available for download at http://genome.nhgri.nih.gov/genemachine. A public Web interface to the GeneMachine server for academic and not-for-profit users is available at http://genemachine.nhgri.nih.gov. The Web supplement to this paper may be found at http://genome.nhgri.nih.gov/genemachine/supplement/.

Contact: andy@nhgri.nih.gov

* To whom correspondence should be addressed.
Critical Assessment of Microarray Data Analysis: the 2001
challenge
Authors: Johnson Kimberly F. , Lin Simon M.
Published: September 2002

Summary: We initiated the Critical Assessment of Microarray Data Analysis (CAMDA) conference to stimulate and evaluate the development of advanced data analysis techniques for microarrays. A standard data set has been released for this data analysis challenge. The goal of this challenge is to assess the performance of different analytical methods and at the same time to determine how such methods should be evaluated. We hope this effort will catalyze the discussion of microarray data analysis among the research community of biologists, statisticians, mathematicians, and computer scientists.

Availability: http://camda.duke.edu

Contact: camda01@canctr.mc.duke.edu;

* To whom correspondence should be addressed.
Improving gene recognition accuracy by combining
predictions from two gene-finding programs
Authors: Rogic Sanja , Ouellette B.F. Francis , Mackworth Alan K.
Published: September 2002

Motivation: Despite constant improvements in prediction accuracy, gene-finding programs are still unable to provide automatic gene discovery with desired correctness. The current programs can identify up to 75% of exons correctly and less than 50% of predicted gene structures correspond to actual genes. New approaches to computational gene-finding are clearly needed.

Results: In this paper we have explored the benefits of combining predictions from already existing gene prediction programs. We have introduced three novel methods for combining predictions from programs Genscan and HMMgene. The methods primarily aim to improve exon level accuracy of gene-finding by identifying more probable exon boundaries and by eliminating false positive exon predictions. This approach results in improved accuracy at both the nucleotide and exon level, especially the latter, where the average improvement on the newly assembled dataset is 7.9% compared to the best result obtained by Genscan and HMMgene. When tested on a long genomic multi-gene sequence, our method that maintains reading frame consistency improved nucleotide level specificity by 21.0% and exon level specificity by 32.5% compared to the best result obtained by either of the two programs individually.

Availability: The scripts implementing our methods are available from http://www.cs.ubc.ca/labs/beta/genefinding/

Contact: rogic@cse.ucsc.edu

* To whom correspondence should be addressed.
Computational identification of putative programmed
translational frameshift sites
Authors: Shah Atul A. , Giddings Michael C. , Parvaz Jasmin B. , Gesteland Raymond F. , Atkins John F. , Ivanov Ivaylo P.
Published: September 2002

Motivation: In an effort to identify potential programmed frameshift sites by statistical analysis, we explore the hypothesis that selective pressure would have rendered such sites underabundant and underrepresented in protein-coding sequences. We developed a computer program to compare the frequencies of k-length subsequences of nucleotides with the frequencies predicted by a zero order Markov chain determined by the codon bias of the same set of sequences. The program was used to calculate and evaluate the distribution of 7-base oligonucleotides in the 6000+ putative protein-coding sequences of S. cerevisiae preliminary to the laboratory testing of the most highly underrepresented oligos for frameshifting efficiency.

Results: Among the most significant results is the finding that the heptanucleotides CUU-AGG-C and CUU-AGU-U, sites of the programmed +1 translational frameshifts required for the production in yeast of actin filament-binding protein ABP140 and telomerase subunit EST3, respectively, rank among the least represented of phase I heptanucleotides in the coding sequences of S. cerevisiae. Laboratory experiments demonstrated that other underrepresented heptanucleotides identified by the program, for example GGU-CAG-A, are also prone to significant translational frameshifting, suggesting the possibility that genes containing other underrepresented heptamers may also encode transframe products.

Availability: The program is available for download from http://www.gesteland.genetics.utah.edu/freqAnalysis

Contact: ivaylo.ivanov@m.cc.utah.edu

Supplementary Information: Complete results from the analysis of S. cerevisiae are available on http://www.gesteland.genetics.utah.edu/freqAnalysis

* To whom correspondence should be addressed.

2 Present address: Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Mapping physiological states from microarray expression measurements
Authors: Stephanopoulos Gregory , Hwang Daehee , Schmitt William A. , Misra Jatin , Stephanopoulos George
Published: September 2002

Motivation: The increasing use of DNA microarrays to probe cell physiology requires methods for visualizing different expression phenotypes and explicitly connecting individual genes to discriminating expression features. Such methods should be robust and maintain biological interpretability.

Results: We propose a method for the mapping of the physiological state of cells and tissues from multidimensional expression data such as those obtained with DNA microarrays. The method uses Fisher discriminant analysis to create a linear projection of gene expression measurements that maximizes the separation of different sample classes. Relative to other typical classification methods, this method provides insights into the discriminating characteristics of expression measurements in terms of the contribution of individual genes to the definition of distinct physiological states. This projection method also facilitates visualization of classification results in a reduced dimensional space. Examples from four different cases demonstrate the ability of the method to produce well-separated groups in the projection space and to identify important genes for defining physiological states. The method can be augmented to also include data from the proteomic and metabolic phenotypes and can be useful in disease diagnosis, drug screening and bioprocessing applications.

Contact: gregstep@mit.edu

* To whom correspondence should be addressed.
A conditional density error model for the statistical
analysis of microarray data
Authors: Love Brad , Rank David R. , Penn Sharron G. , Jenkins David A. , Thomas Russell S.
Published: September 2002

Motivation: In many microarray experiments, relatively few intra- and inter-array replicate measurements are made due to significant cost limitations and sample availability. Compounding this problem is a lack of robust statistical methods for analyzing gene expression data with limited experimental replicates. As a result, the interpretation of the results of these experiments are difficult with little understanding of the probability of type I and type II errors.

Results: The variability in a series of replicate microarray measurements was modelled using a combination of parametric and non-parametric methods. A 3-dimensional surface was created for the conditional distribution of the variability given the mean signal intensity in both the Cy3 and Cy5 channels. The results were used as the basis for developing statistical methods for analyzing gene expression data with limited experimental replicates.

Availability: The statistical analysis scripts are available upon request.

Contact: drblove@yahoo.comrthomas@kalypsys.com

* To whom correspondence should be addressed at Informax Inc., 7600 Wisconsin Avenue, Suite 1100, Bethesda, MD 20814, USA

2 Pressent address: Kalypsys, Inc., 11099 N. Torrey Pines Road, Suite 200, La Jolla, CA 92037, USA

3 Pressent address: Amersham Biosciences, 928 East Arques Avenue, Sunnyvale, CA 94085, USA
Neural network predicts sequence of TP53 gene based on DNA chip
Authors: Spicker Jeppe S. , Wikman Friedrik , Lu Ming-Lan , Cordon-Cardo Carlos , Workman Christopher , Ørntoft Torben F. , Brunak Søren , Knudsen Steen
Published: September 2002

Summary: We have trained an artificial neural network to predict the sequence of the human TP53 tumor suppressor gene based on a p53 GeneChip. The trained neural network uses as input the fluorescence intensities of DNA hybridized to oligonucleotides on the surface of the chip and makes between zero and four errors in the predicted 1300 bp sequence when tested on wild-type TP53 sequence.

Availability: The trained neural network is available for academic use by contacting steen@cbs.dtu.dk

Contact: steen@cbs.dtu.dk

* To whom correspondence should be addressed.
XEMBL: distributing EMBL data in XML format
Authors: Wang Lichun , Riethoven Jean-Jack , Robinson Alan
Published: September 2002

Summary: Data in the EMBL Nucleotide Sequence Database is traditionally available in a flat file format that has a number of known shortcomings. With XML rapidly emerging as a standard data exchange format that can address some problems of flat file formats by defining data structure and syntax, there is now a demand to distribute EMBL data in an XML format. XEMBL is a service tool that employs CORBA servers to access EMBL data, and distributes the data in XML format via a number of mechanisms.

Availability: Use of the XEMBL service is free of charge at http://www.ebi.ac.uk/xembl/, and can be accessed via web forms, CGI, and a SOAP-enabled service.

Contact: lcwang@ebi.ac.ukpow@ebi.ac.ukalan@ebi.ac.uk

Supplementary information: Information on the EMBL Nucleotide Sequence Database is available at http://www.ebi.ac.uk/embl/. The EMBL Object Model is available at http://corba.ebi.ac.uk/models/. Information on the EMBL CORBA servers is at http://corba.ebi.ac.uk/
Murine spermatogonial stem cells: targeted transgene expression and purification in an active state
Authors: Giuili Galicia , Tomljenovic Andrea , Labrecque Nathalie , Oulad‐Abdelghani Mustapha , Rassoulzadegan Minoo , Cuzin François
Published: September 2002

A 400 bp fragment of the spermatogonia‐specific Stra8 locus was sufficient to direct gene expression to the germinal stem cells in transgenic mice. A fractionation procedure was devised, based on immunomagnetic sorting of cells in which the promoter drives the expression of a surface functionally neutral protein tag. The purified cells expressed the known molecular markers of spermatogonia Rbm, cyclin A2 and EP‐Cam, and the β1‐ and α6‐integrins characteristic of the stem cell fraction. A 700‐fold enrichment in stem cells was determined by the ability of the purified fractions to re‐establish spermatogenesis in germ cell‐depleted recipient testes.
The rhodanese/Cdc25 phosphatase superfamily
Authors: Bordo Domenico , Bork Peer
Published: September 2002

Rhodanese domains are ubiquitous structural modules occurring in the three major evolutionary phyla. They are found as tandem repeats, with the C‐terminal domain hosting the properly structured active‐site Cys residue, as single domain proteins or in combination with distinct protein domains. An increasing number of reports indicate that rhodanese modules are versatile sulfur carriers that have adapted their function to fulfill the need for reactive sulfane sulfur in distinct metabolic and regulatory pathways. Recent investigations have shown that rhodanese domains are also structurally related to the catalytic subunit of Cdc25 phosphatase enzymes and that the two enzyme families are likely to share a common evolutionary origin. In this review, the rhodanese/Cdc25 phosphatase superfamily is analyzed. Although the identification of their biological substrates has thus far proven elusive, the emerging picture points to a role for the amino‐acid composition of the active‐site loop in substrate recognition/specificity. Furthermore, the frequently observed association of catalytically inactive rhodanese modules with other protein domains suggests a distinct regulatory role for these inactive domains, possibly in connection with signaling.
New approaches towards the identification of antibiotic and vaccine targets in Streptococcus pneumoniae
Authors: Di Guilmi Anne Marie , Dessen Andréa
Published: September 2002

Streptococcus pneumoniae causes more than one million deaths every year, mostly of young children in developing countries, due to pneumonia, bacteremia and meningitis. The emergence and dissemination of drug‐resistant pneumococcal strains, coupled to changing patterns of virulence and the inadequacy of available vaccines, calls for an aggressive search for novel targets for antibiotic and vaccine development. Microbial genomics techniques allow genetic and biochemical tools to be employed to tackle discovery, design and development of new anti‐infective agents based on the identification of hundreds of new targets. In this review, novel approaches employed to identify potential antibiotic and vaccine targets in S. pneumoniae are highlighted. Recently identified virulence factors, as well as molecules essential for bacterial viability, cell wall integrity and infectivity, are discussed.
Differential involvement of p38 mitogen‐activated protein kinase kinases MKK3 and MKK6 in T‐cell apoptosis
Authors: Tanaka Nobuyuki , Kamanaka Masahito , Enslen Hervé , Dong Chen , Wysk Mark , Davis Roger J , Flavell Richard A
Published: September 2002

The p38 mitogen‐activated protein kinase (p38MAPK) is activated in response to various stimuli, including cellular stress, inflammatory cytokines and cell surface receptors. The activation of p38MAPK is predominantly mediated by the two upstream MAPK kinases MKK3 and MKK6. To study the role of the p38MAPK pathway in vivo, we generated Mkk6−/− mice. We examined whether T‐cell apoptosis is affected in these mice and in our previously reported Mkk3−/− mice. Strikingly, in vivo deletion of double positive thymocytes in Mkk6−/− mice was impaired, whereas Mkk3−/− mice showed no apparent abnormality. Conversely, CD4+T cells from Mkk3−/− but not from Mkk6−/− mice were resistant to activation‐induced cell death and cytokine‐withdrawal‐induced apoptosis. In peripheral CD4+T cells, MKK3 is induced upon stimulation, whereas MKK6 is downregulated. These results suggest a novel mechanism regulating T‐cell apoptosis differentially through the p38MAPK pathway by MKK3 and MKK6.
The Methanobacterium thermoautotrophicum MCM protein can form heptameric rings
Authors: Yu Xiong , VanLoock Margaret S , Poplawski Andrzej , Kelman Zvi , Xiang Tao , Tye Bik K , Egelman Edward H
Published: September 2002

Mini‐chromosome maintenance (MCM) proteins form a conserved family found in all eukaryotes and are essential for DNA replication. They exist as heteromultimeric complexes containing as many as six different proteins. These complexes are believed to be the replicative helicases, functioning as hexameric rings at replication forks. In most archaea a single MCM protein exists. The protein from Methanobacterium thermoautotrophicum (mtMCM) has been reported to assemble into a large complex consistent with a dodecamer. We show that mtMCM can assemble into a heptameric ring. This ring contains a C‐terminal helicase domain that can be fit with crystal structures of ring helicases and an N‐terminal domain of unknown function. While the structure of the ring is very similar to that of hexameric replicative helicases such as bacteriophage T7 gp4, our results show that such ring structures may not be constrained to have only six subunits.
Human replication protein Cdc6 is selectively cleaved by caspase 3 during apoptosis
Authors: Pelizon Cristina , d'Adda di Fagagna Fabrizio , Farrace Lorena , Laskey Ronald A
Published: September 2002

In eukaryotes, the initiation of DNA replication involves the ordered assembly on chromatin of pre‐replicative complexes (pre‐RCs), including the origin recognition complex (ORC), Cdc6, Cdt1 and the minichromosome maintenance proteins (MCMs). In light of its indispensable role in the formation of pre‐RCs, Cdc6 binding to chromatin represents a key step in the regulation of DNA replication and cell proliferation. Here, we study the human Cdc6 (HuCdc6) protein during programmed cell death (apoptosis). We find that HuCdc6, but not HuOrc2 (a member of the ORC) or HuMcm5 (one of the MCMs), is specifically cleaved in several human cell lines induced to undergo apoptosis by a variety of stimuli. Expression of caspase‐uncleavable mutant HuCdc6 attenuates apoptosis, delaying cell death. Therefore, an important function for cleavage of HuCdc6 is to prevent a wounded cell from replicating and to facilitate death.
Recent History of Melanism in American Peppered Moths
Authors: Grant B. S. , Wiseman L. L.
Published: September 2002

Industrial melanism in peppered moths has been studied most intensively in Britain. The first melanic phenotype (effectively solid black) was recorded near Manchester in 1848. By 1895 about 98% of the specimens near Manchester were melanic, and this once rare phenotype had spread across regions of the country blackened by industrial soot. In rural, unpolluted regions, well away from industrial centers, the pale phenotype (peppered with white and black scales) remained the predominant form. During the latter half of the 20th century, following legislation designed to improve air quality, melanics began to decline in frequency and are now rare where once they had been common. Similar evolutionary changes have occurred elsewhere, but records from outside Britain are fragmentary. We have extended previous surveys of American peppered moth populations and present a composite picture of the recent decline in melanism in northern industrial states—Michigan and Pennsylvania—where melanic phenotypes decreased from more than 90% in 1959 to 6% by 2001. We contrast these changes to the near absence of melanism in a southern state—Virginia—during that same period. As in Britain, the decline in melanism in American peppered moths followed clean air legislation.
Delivering HIV Services to Vulnerable Populations: A Review of CARE Act—Funded Research
Authors: McKinney Martha M. , Marconi Katherine M.
Published: September 2002

This article summarizes key findings from evaluation and research studies that have received financial support from the HIV/AIDS Bureau of the Health Resources and Services Administration or from Ryan White Comprehensive AIDS Resources Emergency (CARE) Act grantees. These studies suggest that the CARE Act has improved but not equalized service accessibility, quality, and outcomes for different populations living with HIV disease. Evaluations of access to highly active antiretroviral therapy (HAART) found that uninsured patients, women, people of color, and injection drug users waited much longer than others to receive the new therapies. These disparities were not uniform across study sites, suggesting that clinic characteristics and geographic location have a major influence on prescribing patterns. Once patients gained access to HAART, health insurance status made little difference in clinical outcomes.
A study of corrosion control of carbon steel using inhibitors in a simulated environment
Authors: Kahraman R. , Al‐Mathami A.A. , Saricimen H. , Abbas N. , Rahman S.U.
Published: September 2002

The weather in the Arabian Gulf region constitutes an environment that is corrosive to carbon steel. In the Gulf region, atmospheric corrosion is aggravated further by the high salinity of Gulf sea‐water. In addition, sulphur dioxide and deposits from combustion products tend to make the atmosphere in the Gulf region even more corrosive. Various inhibitors are reported in the literature that can help in the prevention of metal corrosion in aqueous environments. Among these, sodium dihydrogen orthophosphate, sodium benzoate, sodium nitrite and sodium nitrate were obtained and the effectiveness of certain corrosion inhibitors on carbon steel specimens was examined in a simulated atmospheric corrosion environment containing 2% NaCl and 1% Na2SO4 with various inhibitor concentrations. Test specimens were prepared from locally produced carbon steel reinforcing bars. It was found as a result of the test programme that treatment of the steel with 10 or 100mM sodium dihydrogen orthophosphate for one day at room temperature resulted in the best inhibition of corrosion. The results also demonstrated that inhibitors such as sodium benzoate and sodium nitrite were only similarly effective, as was sodium nitrate. Plans further study to examine the inhibition performance of sodium dihydrogen orthophosphate under actual atmospheric conditions.
Evaluating best value through clustered benchmarking in UK local government: building control services
Authors: McAdam Rodney , O’Neill Liam
Published: September 2002

The best value initiative has been designated as the key framework for improving service quality and effectiveness in UK local government. In support of the framework a number of measures have been introduced to measure effectiveness. However, there are problems with using comparative performance measures within the diverse grouping of local government services. Aims to measure the effectiveness of best value in a similar group of building control services by using a clustered benchmarking approach. The mainly qualitative research involves applying a strategic benchmarking approach to the 26 units or councils within the cluster and then comparing the cluster with the best practice UK measures for building control services. To facilitate the process a benchmarking measurement framework for building control was developed. The results indicate that the clustering approach is more beneficial than comparing the service of a single unit with best practice. Practices comparable with best practice for key measures can be identified for individual units or councils within the cluster. Moreover, there are more opportunities for generalising the findings and developing measurement frameworks within clusters. The cluster can internalise the benchmarked findings through mutually supportive programmes.
An analysis of recent trends in Australian local government
Authors: Worthington Andrew C. , Dollery Brian E.
Published: September 2002

Over the past decade Australian local government has undergone drastic change. The sheer pace of reform has made it difficult for practitioners and scholars alike to document and evaluate these rapid changes and even most recent extant analyses are now dated. Given the urgent need to review trends in Australian local government, this paper examines the recent programs of legislative, structural, workplace and financial reform.
SMEs and government purchasing in Northern Ireland: problems and opportunities
Authors: Fee Ruth , Erridge Andrew , Hennigan Sean
Published: September 2002

The aim of the paper is to examine the support mechanisms that exist for small‐ to medium‐sized enterprises (SMEs) in Northern Ireland and how access to government contracts can be improved for SMEs. The paper will investigate the rationale for SME involvement in public procurement, as well as drawing upon a series of interviews carried out with government suppliers in Northern Ireland. This paper concludes that even though there are support mechanisms for SMEs at both a UK and at a European level, government tendering procedures need to be simplified to ensure easier access to contracts for SMEs.
E‐learning communities, virtual markets and knowledge creation
Authors: Hardaker Glenn , Smith David
Published: September 2002

From this push for non‐linear innovation has come a fragmented market of hardware, software, and services branded as, knowledge‐management solutions. Virtual knowledge networks provide a dynamic way of working relevant for the emergence of a post‐industrial economy. E‐learning is seen as a driver of knowledge creation across unstructured virtual communities. The paper considers the role of managed learning environments (MLEs) in the context of information‐intensive organisations operating in virtual markets (software, publishing, education, music, consultancy services plus many more), the relationship with knowledge creation across distributed networks, and finally strategies for building knowledge networks through the creation of e‐learning communities.
Culture in defining consumer satisfaction in marketing
Authors: Vranesevic Tihomir , Vignali Claudio , Vignali Daniella
Published: September 2002

The objectives of this article are to explain the importance of company culture and to point to the appropriateness of customer orientation as a method of expressing culture. The article further determines the connection between customer satisfaction and employee satisfaction and points to possible resistance when creating company culture through customer orientation. It further defines the relation between company mission and culture and explains the significance of researching value and researching customer satisfaction as basic preconditions of customer orientation in culture.
WJU’s Challenger Learning Center: using technology to impact on education world‐wide
Authors: Rejonis Michele
Published: September 2002

Looks at the Challenger Learning Center in West Virginia, USA, and its e‐Mission: Operation Monserrat Island, a distance learning program designed to meet state and national standards in the areas of maths and science in grades 6 through 12. States that this is done via the Internet with the use of computers and a small camera. Concludes that this is a unique hands‐on learning experience with the potential to reach a great number of students.
A longitudinal study of data management practices among parks management students
Authors: Spennemann Dirk H.R. , Atkinson John S.
Published: September 2002

This paper details a longitudinal study into the data management practices of first year students at Charles Sturt University. This study is part of ongoing research investigating the factors and barriers that can influence the successful adoption of technology into the learning environment. The findings suggest that students are exhibiting poor data management skills and lack the understanding to recover from data loss situations.
Global virtual teams: what impacts their design and performance?
Authors: Prasad Krishna , Akhilesh K.B.
Published: September 2002

This paper examines the aspect of designing global virtual teams and the key factors that impact team design. Examines how design impacts team performance. Proposes a conceptual model for designing such teams to deliver optimal performance. The model contains four major elements: virtual team structure, strategic objectives, work characteristics and situational constraints. The impact of the last three elements on team structure and their relationship to team performance are examined. Proposes a multi‐dimensional measure for virtual team structure, and considers how situational demands and performance constraints can impact team design. Highlights the fact that performance of teams too is multi‐dimensional and design has to consider the tradeoff involved in these factors. Proposes that global virtual teams be designed with a holistic approach considering an optimal fit between the team structure and the key impacting factors like objectives, work characteristics and situational constraints to deliver performance.
Fostering a career development culture: reflections on the roles of managers, employees and supervisors
Authors: Conger Stuart
Published: September 2002

The culture of an organization can be positive and supportive, or threatening and destructive. A career development culture helps address productivity, competitiveness, affirmative action, and succession planning. It helps people redefine their talents to realize the full potential of their jobs. Supervisors should play a key role in creating a career development culture, but many feel their careers are going nowhere and see career development efforts to be an added burden. Supervisors seldom do performance appraisals properly because they are afraid of their workers and the workers are virtually paranoid about the slightest negative note on their files. A better way is to organize a system of mentorship. Evaluation of initiatives can be calculated on the basis of savings that can be attributed to the program and its actual costs. A managed career development culture can pay great rewards to an organization and the people working in it.
Heterogeneous expression of transient outward currents in smooth muscle cells of the mouse small intestine
Authors: Lee Jonathan C. F. , Barajas‐López Carlos , Huizinga Jan D.
Published: September 2002

The objective for this paper was to characterize the transient outward current (Ito) present in smooth muscle cells of the intestinal external muscularis. Two populations of cells were identified, one with a fast rate of Ito inactivation (τ < 100 ms) and another with a slow rate of Ito inactivating (τ > 150 ms). The chord conductance for the fast Ito was smaller than the chord conductance of the slow Ito (0.5 ± 0.1 vs. 1.3 ± 0.1 nS pF−1, respectively). The inactivation was fitted by mono‐exponentials to give a τ for the fast and slow Ito of 44 and 229 ms, respectively. Combined plots of voltage dependent activation and inactivation processes revealed voltage ranges where window currents were possible; a 20 mV range for the fast Ito from −56 to −36 mV and a 47 mV range for the slow Ito from −42 to +5 mV. The fast Ito recovered more quickly from inactivation than the slow Ito; τ(fast Ito) = 11 ± 4 ms compared to τ(slow Ito) = 42 ± 16 ms. The effect of different rates of depolarization on Ito activation was examined. The plots of peak currents evoked by different rates of depolarization were well fitted by inverse exponential functions. The fast Ito had a larger response to fast rates of depolarization by having a τ of 2 ± 1 mV ms−1 with maximal activation (95 % complete) at 5 mV ms−1. The slow Ito had a τ of 14 ± 9 mV ms−1 with maximal activation (95 % complete) at 42 mV ms−1. The properties of these currents suggest that the two transient outward currents may contribute differently to slow waves and action potentials generated by the smooth muscle cells.
Nitric oxide plays a role in the regulation of adrenal blood flow and adrenocorticomedullary functions in the llama fetus
Authors: Riquelme Raquel A. , Sánchez Gina , Liberona Leonel , Sanhueza Emilia M. , Giussani Dino A. , Blanco Carlos E. , Hanson Mark A. , Llanos Aníbal J.
Published: September 2002

The hypothesis that nitric oxide plays a key role in the regulation of adrenal blood flow and plasma concentrations of cortisol and catecholamines under basal and hypoxaemic conditions in the llama fetus was tested. At 0.6‐0.8 of gestation, 11 llama fetuses were surgically prepared for long‐term recording under anaesthesia with vascular and amniotic catheters. Following recovery all fetuses underwent an experimental protocol based on 1 h of normoxaemia, 1 h of hypoxaemia and 1 h of recovery. In nine fetuses, the protocol occurred during fetal i.v. infusion with saline and in five fetuses during fetal i.v. treatment with the nitric oxide synthase inhibitor l‐NAME. Adrenal blood flow was determined by the radiolabelled microsphere method during each of the experimental periods during saline infusion and treatment with l‐NAME. Treatment with l‐NAME during normoxaemia led to a marked fall in adrenal blood flow and a pronounced increase in plasma catecholamine concentrations, but it did not affect plasma ACTH or cortisol levels. In saline‐infused fetuses, acute hypoxaemia elicited an increase in adrenal blood flow and in plasma ACTH, cortisol, adrenaline and noradrenaline concentrations. Treatment with l‐NAME did not affect the increase in fetal plasma ACTH, but prevented the increments in adrenal blood flow and in plasma cortisol and adrenaline concentrations during hypoxaemia in the llama fetus. In contrast, l‐NAME further enhanced the increase in fetal plasma noradrenaline. These data support the hypothesis that nitric oxide has important roles in the regulation of adrenal blood flow and adrenal corticomedullary functions during normoxaemia and hypoxaemia functions in the late gestation llama fetus.
Slow phases of GABAA receptor desensitization: structural determinants and possible relevance for synaptic function
Authors: Bianchi Matt T. , Macdonald Robert L.
Published: September 2002

GABAA receptor fast desensitization is thought to shape the time course of individual IPSCs. Although GABAA receptors also exhibit slower phases of desensitization, the possible role of slow desensitization in modifying synaptic function is poorly understood. In transiently transfected human embryonic kidney (HEK293T) cells, rat α1β3δ and α1β3γ2L GABAA receptors showed distinct desensitization patterns during long (28 s) concentration jumps using a saturating (1 mm) GABA concentration. α1β3γ2L receptors desensitized extensively (≈90 %), with four phases (τ1≈20 ms, τ2≈400 ms, τ3≈2 s, τ4≈10 s), while α1β3δ receptors desensitized slowly and less extensively (≈35 %), with one or two slow phases with time constants similar to τ3 and τ4 of α1β3γ2L receptors. To determine the structural basis of subunit‐specific desensitization, δ‐γ2L chimera subunits were expressed with α1 and β3 subunits. Replacing the entire N‐terminus of the γ2L subunit with δ subunit sequence did not alter the number of phases or the extent of desensitization. Although extension of δ subunit sequence into transmembrane domain 1 (TM1) abolished the fast and intermediate components of desensitization, the two slow phases still accounted for substantial current loss (≈65 %). However, when δ subunit sequence was extended through TM2, the extent of desensitization was significantly decreased and indistinguishable from that of α1β3δ receptors. The importance of TM2 sequence was confirmed by introducing γ2 subunit TM2 residues into the δ subunit, which significantly increased the extent of desensitization, without introducing either the fast or intermediate desensitization phases. However, introducing δ subunit TM2 sequence into the γ2L subunit had minimal effect on the rates or extent of desensitization. The results suggest that distinct δ subunit structures are responsible for its unique desensitization properties: lack of fast and intermediate desensitization and small contribution of the slow phases of desensitization. Finally, to investigate the possible role of slow desensitization in synaptic function, we used a pulse train protocol. We observed inhibition of peak current amplitude that depended on the frequency and duration of GABA pulses for receptors exhibiting extensive desensitization, whether fast phases were present or not. The minimally desensitizing α1β3δ receptor exhibited negligible inhibition during pulse trains. Because receptors that desensitized without the fast and intermediate phases showed pulse train inhibition, we concluded that receptors can accumulate in slowly equilibrating desensitized states during repetitive receptor activation. These results may indicate a previously unrecognized role for the slow phases of desensitization for synaptic function under conditions of repeated GABAA receptor activation.
Difference between hypoglossal and phrenic activities during lung inflation and swallowing in the rat
Authors: Saito Yoshiaki , Ezure Kazuhisa , Tanaka Ikuko
Published: September 2002

We aimed in this study to elucidate the discharge properties and neuronal mechanisms of the dissociation between hypoglossal and phrenic inspiratory activities in decerebrate rats, which had been subjected to neuromuscular blockade and artificially ventilated. The discharge of the hypoglossal nerve and the intracellular activity of hypoglossal motoneurones were monitored during respiration and fictive‐swallowing evoked by electrical stimulation of the superior laryngeal nerve, and were compared with the activity of the phrenic nerve. The hypoglossal nerve activity was characterized by its onset preceding the phrenic nerve activity (‘pre‐I’ activity). By manipulating artificial respiration, we could augment the ‘pre‐I’ activity, and could elicit another type of hypoglossal activity decoupled from the phrenic‐associated inspiratory bursts (‘decoupled’ activity). We further scrutinized the correlatives of ‘pre‐I’ and ‘decoupled’ activities in individual hypoglossal motoneurones. Hypoglossal motoneurones consisted of inspiratory (n= 42), expiratory (n= 18) and non‐respiratory (n= 1) neurones and were classified by their swallowing activity into depolarized, hyperpolarized, hyperpolarized‐depolarized and unresponsive groups. All of the inspiratory neurones were depolarized in accordance with the ‘pre‐I’ and ‘decoupled’ activities, and all of the expiratory neurones were hyperpolarized during these activities. Fictive swallowing, which was characterized by its frequent emergence just after the phrenic inspiratory activity, was also evoked just after the ‘decoupled’ hypoglossal activity, suggesting that this activity may have similar effects on swallowing as the ‘overt’ inspiratory activity. Such a coupling between ‘decoupled’ and swallowing activities was also revealed in each motoneurone. These findings suggest that the ‘pre‐I’ and ‘decoupled’ activities may reflect some internal inspiratory activity of the respiratory centre and that hypoglossal motoneurones may be driven by a distinct group of premotor neurones that possibly play a role in the coordination of respiration and swallowing.
Activation of store‐operated channels by noradrenaline via protein kinase C in rabbit portal vein myocytes
Authors: Albert A. P. , Large W. A.
Published: September 2002

In the present study we have investigated the role of diacylglycerol (DAG) and protein kinase C (PKC) in mediating activation of Ca2+‐permeable store‐operated channels (SOCs) by noradrenaline in rabbit portal vein smooth muscle cells. With cell‐attached recording, bath application of noradrenaline, 1‐oleoyl‐acetyl‐sn‐glycerol (OAG) and phorbol 12,13‐dibutyrate (PDBu) evoked single channel currents. The biophysical properties of these channel currents were similar to those of the channel currents activated by depletion of internal Ca2+ stores with cyclopiazonic acid (CPA). The activation of SOCs in cell‐attached recording by noradrenaline, OAG, PDBu, CPA and the acetoxymethyl ester form of BAPTA (BAPTA‐AM) was markedly inhibited by the PKC inhibitors chelerythrine and RÖ‐31‐8220. In isolated outside‐out patches CPA did not evoke SOCs but noradrenaline stimulated SOC activity, which was reduced by about 90 % by PKC inhibitors. The addition of the serine/threonine phosphatase inhibitors calyculin A and microcystin also stimulated SOCs in isolated outside‐out patches. It is concluded that in rabbit portal vein myocytes, noradrenaline activates SOCs via DAG and PKC, possibly by a store‐independent mechanism. In addition in this cell type it appears that PKC and phosphorylation may play an important role in stimulating SOC activity in response to depletion of internal Ca2+ stores by CPA and BAPTA‐AM.
Effects of respiratory alkalosis on human skeletal muscle metabolism at the onset of submaximal exercise
Authors: LeBlanc P. J. , Parolin M. L. , Jones N. L. , Heigenhauser G. J. F.
Published: September 2002

The purpose of this study was to examine the effects of respiratory alkalosis on human skeletal muscle metabolism at rest and during submaximal exercise. Subjects exercised on two occasions for 15 min at 55 % of their maximal oxygen uptake while either hyperventilating (R‐Alk) or breathing normally (Con). Muscle biopsies were taken at rest and after 1 and 15 min of exercise. At rest, no effects on muscle metabolism were observed in response to R‐Alk. In the first minute of exercise, there was a delayed activation of pyruvate dehydrogenase (PDH) in R‐Alk compared with Con, resulting in a reduced rate of pyruvate oxidation. Also, glycogenolysis was higher in R‐Alk compared with Con, which was attributed to a higher availability of the monoprotonated form of inorganic phosphate (Pi), resulting in an elevated rate of pyruvate production. The mismatch between pyruvate production and its oxidation resulted in net lactate accumulation. These effects were not seen after 15 min of exercise, with no further differences in muscle metabolism between conditions. The results from the present study suggest that respiratory alkalosis may play an important role in lactate accumulation during the transition from rest to exercise in acute hypoxic conditions, but that other factors mediate lactate accumulation during steady‐state exercise.
Rapid adenosine release in the nucleus tractus solitarii during defence response in rats: real‐time measurement in vivo
Authors: Dale Nicholas , Gourine Alexander V. , Llaudet Enrique , Bulmer David , Thomas Teresa , Spyer K. Michael
Published: September 2002

We have measured the release of adenosine and inosine from the dorsal surface of the brainstem and from within the nucleus tractus solitarii (NTS) during the defence response evoked by hypothalamic stimulation in the anaesthetised rat. At the surface of the brainstem, only release of inosine was detected on hypothalamic defence area stimulation. This inosine signal was greatly reduced by addition of the ecto‐5′‐nucleotidase inhibitor α,β‐methylene ADP (200 μM), suggesting that the inosine arose from adenosine that was produced in the extracellular space by the prior release of ATP. By placing a microelectrode biosensor into the NTS under stereotaxic control we have recorded release of adenosine within this nucleus. By contrast to the brainstem surface, a fast increase in adenosine, accompanied only by a much smaller change in inosine levels, was seen following stimulation of the hypothalamic defence area. The release of adenosine following hypothalamic stimulation was mainly confined to a narrow region of the NTS some 500 μm in length around the level of the obex. Interestingly the release of adenosine was depletable: when the defence reaction was evoked at short time intervals, much less adenosine was released on the second stimulus. Our novel techniques have given unprecedented real‐time measurement and localisation of adenosine release in vivo and demonstrate that adenosine is released at the right time and in sufficient quantities to contribute to the cardiovascular components of the defence reaction.