bluuebunny/crossref_metadata_2025 huggingface dataset:
The ubiquitin proteasome system in synaptic and axonal degeneration
Authors: Korhonen Laura , Lindholm Dan
Published: April 2004

The ubiquitin proteasome system (UPS) contributes to the pathophysiology of neurodegenerative diseases, and it is also a major determinant of synaptic protein degradation and activity. Recent studies in rodents and in the fruit fly Drosophila have shown that the activity of the UPS is involved in axonal degeneration. Increased knowledge of the UPS in synaptic and axonal reactions may provide novel drug targets for treatments of neuronal injuries and neurodegenerative disorders.
PI-3K and Akt are mediators of AP-1 induction by 5-MCDE in mouse epidermal Cl41 cells
Authors: Li Jingxia , Chen Haobin , Tang Moon-Shong , Shi Xianglin , Amin Shantu , Desai Dhimant , Costa Max , Huang Chuanshu
Published: April 2004

5-Methylchrysene has been found to be a complete carcinogen in laboratory animals. However, the tumor promotion effects of (±)-anti-5-methylchrysene-1,2-diol-3,4-epoxide (5-MCDE) remain unclear. In the present work, we found that 5-MCDE induced marked activator protein-1 (AP-1) activation in Cl41 cells. 5-MCDE also induced a marked activation of phosphatidylinositol 3-kinase (PI-3K). Inhibition of PI-3K impaired 5-MCDE–induced AP-1 transactivation, suggesting that PI-3K is an upstream kinase involved in AP-1 activation by 5-MCDE. Furthermore, we found that Akt is a PI-3K downstream mediator for 5-MCDE–induced AP-1 transactivation, whereas another PI-3K downstream kinase, p70S6K, was not involved in AP-1 activation by 5-MCDE. Moreover, inhibition of Akt activation blocked 5-MCDE–induced activation of extracellular signal–regulated protein kinases (ERKs) and c-Jun NH2-terminal kinases (JNKs), whereas it did not affect p38K activation. Consistently, overexpression of a dominant-negative mutant of ERK2 or JNK1 blocked the AP-1 activation by 5-MCDE. These results demonstrate that 5-MCDE is able to induce AP-1 activation, and the AP-1 induction is specifically through a PI-3K/Akt–dependent and p70S6K-independent pathway.
Role of YidC in folding of polytopic membrane proteins
Authors: Nagamori Shushi , Smirnova Irina N. , Kaback H. Ronald
Published: April 2004

YidC of Echerichia coli, a member of the conserved Alb3/Oxa1/YidC family, is postulated to be important for biogenesis of membrane proteins. Here, we use as a model the lactose permease (LacY), a membrane transport protein with a known three-dimensional structure, to determine whether YidC plays a role in polytopic membrane protein insertion and/or folding. Experiments in vivo and with an in vitro transcription/translation/insertion system demonstrate that YidC is not necessary for insertion per se, but plays an important role in folding of LacY. By using the in vitro system and two monoclonal antibodies directed against conformational epitopes, LacY is shown to bind the antibodies poorly in YidC-depleted membranes. Moreover, LacY also folds improperly in proteoliposomes prepared without YidC. However, when the proteoliposomes are supplemented with purified YidC, LacY folds correctly. The results indicate that YidC plays a primary role in folding of LacY into its final tertiary conformation via an interaction that likely occurs transiently during insertion into the lipid phase of the membrane.
Dynein-mediated Vesicle Transport Controls IntracellularSalmonellaReplication
Authors: Marsman Marije , Jordens Ingrid , Kuijl Coen , Janssen Lennert , Neefjes Jacques
Published: April 2004

Salmonella typhimurium survives and replicates intracellular in a membrane-bound compartment, the Salmonella-containing vacuole (SCV). In HeLa cells, the SCV matures through interactions with the endocytic pathway, but Salmonella avoids fusion with mature lysosomes. The exact mechanism of the inhibition of phagolysosomal fusion is not understood. Rab GTPases control several proteins involved in membrane fusion and vesicular transport. The small GTPase Rab7 regulates the transport of and fusion between late endosomes and lysosomes and associates with the SCV. We show that the Rab7 GTPase cycle is not affected on the SCV. We then manipulated a pathway downstream of the small GTPase Rab7 in HeLa cells infected with Salmonella. Expression of the Rab7 effector RILP induces recruitment of the dynein/dynactin motor complex to the SCV. Subsequently, SCV fuse with lysosomes. As a result, the intracellular replication of Salmonella is inhibited. Activation of dynein-mediated vesicle transport can thus control intracellular survival of Salmonella.
Macrophage Surface Expression of Annexins I and II in the Phagocytosis of Apoptotic Lymphocytes
Authors: Fan Xiaoxuan , Krahling Stephen , Smith Douglas , Williamson Patrick , Schlegel Robert A.
Published: April 2004

When cells undergo apoptosis, or programmed cell death, they expose phosphatidylserine (PS) on their surface. Macrophages that efficiently phagocytose apoptotic cells also express PS on their surface, although at a lower level. The PS exposed on both cells is required for phagocytosis, because uptake is inhibited by masking PS on either cell with annexin V, a PS-binding protein. The inhibition is not additive, suggesting that the exposed PS molecules on the two cells participate in a common process. We asked whether this dual requirement reflects bridging of the target cell and macrophage by bivalent, PS-binding annexins. Monoclonal antibodies (mAbs) against annexins I or II stained a variety of live phagocytes. Apoptotic Jurkat T lymphocytes and human peripheral T lymphocytes, but not apoptotic thymocytes, were stained by anti-annexin I but not II. Phagocytosis of apoptotic targets was inhibited by mAbs to annexins I or II, or by pretreatment of macrophages with the same mAbs. Pretreatment of apoptotic thymocytes had no effect, whereas pretreating Jurkat cells with anti-annexin I or removing annexin I with EGTA was inhibitory. Annexin bridging is vectorial, because annexin is bound to PS molecules on targets but not on macrophages, suggesting annexins serve as both ligand and receptor in promoting phagocytosis.
Oda5p, a Novel Axonemal Protein Required for Assembly of the Outer Dynein Arm and an Associated Adenylate Kinase
Authors: Wirschell Maureen , Pazour Gregory , Yoda Akinori , Hirono Masafumi , Kamiya Ritsu , Witman George B.
Published: April 2004

Of the uncloned ODA genes required for outer dynein arm assembly in Chlamydomonas, ODA5 and ODA10 are of particular interest because they do not encode known subunits of the outer arm or the outer dynein arm-docking complex (ODA-DC), and because genetic studies suggest their products interact. Beginning with a tagged oda5 allele, we isolated genomic and cDNA clones of the wild-type gene. ODA5 predicts a novel, 66-kDa coiled-coil protein. Immunoblotting indicates Oda5p is an axonemal component that assembles onto the axoneme independently of the outer arm and ODA-DC and is uniquely missing in oda5 and oda10 axonemes. Oda5p is released from the axoneme by extraction with 0.6 M KCl, but the soluble Oda5p does not cosediment with the outer dynein arm/ODA-DC in sucrose gradients. Quantitative mass spectrometry by using isotope coded affinity tagging revealed that a previously unidentified adenylate kinase is reduced 35–50% in oda5 flagella. Direct enzymatic assays demonstrated a comparable reduction in adenylate kinase activity in oda5 flagella, and also in oda10 flagella, but not in flagella of other oda mutants. We propose that Oda5p is part of a novel axonemal complex that is required for outer arm assembly and anchors adenylate kinase in proximity to the arm.
Diacylglycerol-dependent Binding Recruits PKCθ and RasGRP1 C1 Domains to Specific Subcellular Localizations in Living T Lymphocytes
Authors: Carrasco Silvia , Merida Isabel
Published: April 2004

Diacylglycerol (DAG) signaling relies on the presence of conserved domain 1 (C1) in its target proteins. Phospholipase C–dependent generation of DAG after T cell receptor (TCR) triggering is essential for the correct immune response onset. Accordingly, two C1-containing proteins expressed in T lymphocytes, Ras guanyl nucleotide-releasing protein1 (RasGRP1) and protein kinase Cθ (PKCθ), were shown to be fundamental for T-cell activation and proliferation. Although containing the same regulatory domain, they are proposed to relocate to distinct subcellular locations in response to TCR triggering. Here we studied intracellular localization of RasGRP1 and PKCθ C1 domains in living Jurkat T cells. The results demonstrate that, in the absence of significant primary sequence differences, the C1 domains of these proteins show specific localization within the cell and distinct responses to pharmacological stimulation and TCR triggering. These differences help explain the divergent localization and distinct functional roles of the full-length proteins, which contains them. The properties of these DAG-binding modules allow their characterization as functional markers that discriminate between DAG pools. Finally, we show that by binding to different diacylglycerol forms, overexpression of distinct C1 modules can attenuate DAG-dependent signals originating from the plasma or internal membranes. This is shown by analyzing the contribution of these two lipid pools to PLC-dependent Ras activation in response to TCR triggering.
The Role of Osteoprotegerin and Tumor Necrosis Factor-related Apoptosis-inducing Ligand in Human Microvascular Endothelial Cell Survival
Authors: Pritzker L. B. , Scatena M. , Giachelli C. M.
Published: April 2004

Endothelial cell survival and antiapoptotic pathways, including those stimulated by extracellular matrix, are critical regulators of vasculogenesis, angiogenesis, endothelial repair, and shear-stress-induced endothelial activation. One of these pathways is mediated by αvβ3integrin ligation, downstream activation of nuclear factor-κB, and subsequent up-regulation of osteoprotegerin (OPG). In this study, the mechanism by which OPG protects endothelial cells from death was examined. Serum-starved human microvascular endothelial cells (HMECs) plated on the αvβ3ligand osteopontin were protected from cell death. Immunoprecipitation experiments indicated that OPG formed a complex with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in HMECs under these conditions. Furthermore, inhibitors of TRAIL, including recombinant soluble TRAIL receptors and a neutralizing antibody against TRAIL, blocked apoptosis of serum-starved HMECs plated on the nonintegrin attachment factor poly-d-lysine. Whereas TRAIL was unable to induce apoptosis in HMECs plated on osteopontin, the addition of recombinant TRAIL did increase the percentage of apoptotic HMECs plated on poly-d-lysine. This evidence indicates that OPG blocks endothelial cell apoptosis through binding TRAIL and preventing its interaction with death-inducing TRAIL-receptors
Tropomyosin and Troponin Are Required for Ovarian Contraction in theCaenorhabditis elegansReproductive System
Authors: Ono Kanako , Ono Shoichiro
Published: April 2004

Ovulation in the nematode Caenorhabditis elegans is coordinated by interactions between the somatic gonad and germ cells. Myoepithelial sheath cells of the proximal ovary are smooth muscle-like cells, but the regulatory mechanism of their contraction is unknown. We show that contraction of the ovarian muscle requires tropomyosin and troponin, which are generally major actin-linked regulators of contraction of striated muscle. RNA interference of tropomyosin or troponin C caused sterility by inhibiting ovarian contraction that is required for expelling mature oocytes into the spermatheca where fertilization takes place, thus causing accumulation of endomitotic oocytes in the ovary. Tropomyosin and troponin C were associated with actin filaments in the myoepithelial sheath, and the association of troponin C with actin was dependent on tropomyosin. A mutation in the actin depolymerizing factor/cofilin gene suppressed the ovulation defects by RNA interference of tropomyosin or troponin C. These results strongly suggest that tropomyosin and troponin are the actin-linked regulators for contraction of ovarian muscle in the C. elegans reproductive system.
SCANMS: adjusting for multiple comparisons in sliding window neutrality tests
Authors: Ardell David H.
Published: April 2004

Summary: A Perl utility called SCANMS was written that operates on parametric bootstrap data generated by Hudson's simulator MS. SCANMS simulates sliding window analysis of Tajima's D or Fu and Li's D* or F* over the replicates and generates the empirical joint distribution of window minima and maxima. This distribution may then be used to calculate achieved significance values or significance cutoffs that account for multiple comparisons in sliding window analysis of real data.

Availability: SCANMS is available free of charge under the terms of the Academic Free License 2.0 and may be downloaded from http://www.lcb.uu.se/~dave/SCANMS
ProMode: a database of normal mode analyses on protein molecules with a full-atom model
Authors: Wako Hiroshi , Kato Masaki , Endo Shigeru
Published: April 2004

Motivation: Although information from protein dynamics simulation is important to understand principles of architecture of a protein structure and its function, simulations such as molecular dynamics and Monte Carlo are very CPU-intensive. Although the ability of normal mode analysis (NMA) is limited because of the need for a harmonic approximation on which NMA is based, NMA is adequate to carry out routine analyses on many proteins to compute aspects of the collective motions essential to protein dynamics and function. Furthermore, it is hoped that realistic animations of the protein dynamics can be observed easily without expensive software and hardware, and that the dynamic properties for various proteins can be compared with each other.

Results:  ProMode, a database collecting NMA results on protein molecules, was constructed. The NMA calculations are performed with a full-atom model, by using dihedral angles as independent variables, faster and more efficiently than the calculations using Cartesian coordinates. In ProMode, an animation of the normal mode vibration is played with a free plug-in, Chime (MDL Information Systems, Inc.). With the full-atom model, the realistic three-dimensional motions at an atomic level are displayed with Chime. The dynamic domains and their mutual screw motions defined from the NMA results are also displayed. Properties for each normal mode vibration and their time averages, e.g. fluctuations of atom positions, fluctuations of dihedral angles and correlations between the atomic motions, are also presented graphically for characterizing the collective motions in more detail.

Availability:  http://promode.socs.waseda.ac.jp
TIP: protein backtranslation aided by genetic algorithms
Authors: Moreira Andrés , Maass Alejandro
Published: April 2004

Summary: Several applications require the backtranslation of a protein sequence into a nucleic acid sequence. The degeneracy of the genetic code makes this process ambiguous; moreover, not every translation is equally viable. The usual answer is to mimic the codon usage of the target species; however, this does not capture all the relevant features of the ‘genomic styles’ from different taxa. The program TIP ‘ Traducción Inversa de Proteínas’) applies genetic algorithms to improve the backtranslation, by minimizing the difference of some coding statistics with respect to their average value in the target.

Availability:  http://www.cmm.uchile.cl/genoma/tip/
Fragment assembly with short reads
Authors: Chaisson Mark , Pevzner Pavel , Tang Haixu
Published: April 2004

Motivation: Current DNA sequencing technology produces reads of about 500–750 bp, with typical coverage under 10×. New sequencing technologies are emerging that produce shorter reads (length 80–200 bp) but allow one to generate significantly higher coverage (30× and higher) at low cost. Modern assembly programs and error correction routines have been tuned to work well with current read technology but were not designed for assembly of short reads.

Results: We analyze the limitations of assembling reads generated by these new technologies and present a routine for base-calling in reads prior to their assembly. We demonstrate that while it is feasible to assemble such short reads, the resulting contigs will require significant (if not prohibitive) finishing efforts.

Availability: Available from the web at http://www.cse.ucsd.edu/groups/bioinformatics/software.html
Molecular Genetics Information System (MOLGENIS): alternatives in developing local experimental genomics databases
Authors: Swertz Morris A. , de Brock E. O. (Bert) , van Hijum Sacha A. F. T. , de Jong Anne , Buist Girbe , Baerends Richard J. S. , Kok Jan , Kuipers Oscar P. , Jansen Ritsert C.
Published: April 2004

Motivation: Genomic research laboratories need adequate infrastructure to support management of their data production and research workflow. But what makes infrastructure adequate? A lack of appropriate criteria makes any decision on buying or developing a system difficult. Here, we report on the decision process for the case of a molecular genetics group establishing a microarray laboratory.

Results: Five typical requirements for experimental genomics database systems were identified: (i) evolution ability to keep up with the fast developing genomics field; (ii) a suitable data model to deal with local diversity; (iii) suitable storage of data files in the system; (iv) easy exchange with other software; and (v) low maintenance costs. The computer scientists and the researchers of the local microarray laboratory considered alternative solutions for these five requirements and chose the following options: (i) use of automatic code generation; (ii) a customized data model based on standards; (iii) storage of datasets as black boxes instead of decomposing them in database tables; (iv) loosely linking to other programs for improved flexibility; and (v) a low-maintenance web-based user interface. Our team evaluated existing microarray databases and then decided to build a new system, Molecular Genetics Information System (MOLGENIS), implemented using code generation in a period of three months. This case can provide valuable insights and lessons to both software developers and a user community embarking on large-scale genomic projects.

Availability:  http://www.molgenis.nl
Gene annotation from scientific literature using mappings between keyword systems
Authors: Pérez Antonio J. , Perez-Iratxeta Carolina , Bork Peer , Thode Guillermo , Andrade Miguel A.
Published: April 2004

Motivation: The description of genes in databases by keywords helps the non-specialist to quickly grasp the properties of a gene and increases the efficiency of computational tools that are applied to gene data (e.g. searching a gene database for sequences related to a particular biological process). However, the association of keywords to genes or protein sequences is a difficult process that ultimately implies examination of the literature related to a gene.

Results: To support this task, we present a procedure to derive keywords from the set of scientific abstracts related to a gene. Our system is based on the automated extraction of mappings between related terms from different databases using a model of fuzzy associations that can be applied with all generality to any pair of linked databases. We tested the system by annotating genes of the SWISS-PROT database with keywords derived from the abstracts linked to their entries (stored in the MEDLINE database of scientific references). The performance of the annotation procedure was much better for SWISS-PROT keywords (recall of 47%, precision of 68%) than for Gene Ontology terms (recall of 8%, precision of 67%).

Availability: The algorithm can be publicly accessed and used for the annotation of sequences through a web server at http://www.bork.embl.de/kat
Extraction of fluorescent cell puncta by adaptive fuzzy segmentation
Authors: Pham Tuan D. , Crane Denis I. , Tran Tuan H. , Nguyen Tam H.
Published: April 2004

Motivation: The discrimination and measurement of fluorescent-labeled vesicles using microscopic analysis of fixed cells presents a challenge for biologists interested in quantifying the abundance, size and distribution of such vesicles in normal and abnormal cellular situations. In the specific application reported here, we were interested in quantifying changes to the population of a major organelle, the peroxisome, in cells from normal control patients and from patients with a defect in peroxisome biogenesis. In the latter, peroxisomes are present as larger vesicular structures with a more restricted cytoplasmic distribution. Existing image processing methods for extracting fluorescent cell puncta do not provide useful results and therefore, there is a need to develop some new approaches for dealing with such a task effectively.

Results: We present an effective implementation of the fuzzy c-means algorithm for extracting puncta (spots), representing fluorescent-labeled peroxisomes, which are subject to low contrast. We make use of the quadtree partition to enhance the fuzzy c-means based segmentation and to disregard regions which contain no target objects (peroxisomes) in order to minimize considerable time taken by the iterative process of the fuzzy c-means algorithm. We finally isolate touching peroxisomes by an aspect-ratio criterion. The proposed approach has been applied to extract peroxisomes contained in several sets of color images and the results are superior to those obtained from a number of standard techniques for spot extraction.

Availability: Image data and computer codes written in Matlab are available upon request from the first author.
Bio-Mirror project for public bio-data distribution
Authors: Gilbert Don , Ugawa Yoshihiro , Buchhorn Markus , Wee Tan Tin , Mizushima Akira , Kim Hyunchul , Chon Kilnam , Weon Seyeon , Ma Juncai , Ichiyanagi Yoshihiro , Liou Der-Ming , Keretho Somnuk , Napis Suhaimi
Published: April 2004

Summary: Timely worldwide distribution of biosequence and bioinformatics data depends on high performance networking and advances in Internet transport methods. The Bio-Mirror project focuses on providing up-to-date distribution of this rapidly growing and changing data. It offers FTP, Web and Rsync access to many high-volume databanks from several sites around the world. Experiments with data grids and other methods offer future improvements in biology data distribution.

Availability:  http://www.bio-mirror.net/
Design and implementation of a mosquito database through an entomological ontology
Authors: Koum Guillaume , Yekel Augustin , Ndifon Bengyella , Simard Frédéric
Published: April 2004

Summary: There have been constant changes in the biology and behavior of the vector and parasite involved in the transmission of malaria. There is limited interest in developing new technologies and procedures for controlling the underlying factors of this threat, which poses an enormous challenge to health systems. To understand the various vector species and their interrelations is of prime importance in understanding the transmission mechanisms of malaria in order to react efficiently. To attain this objective, we have used an ontological approach to producing a database that we consider to be our own contribution in helping to control malaria vectors if eradication has been unsuccessful in the previous control campaign.
A database for management of gene expression data in situ
Authors: Poustelnikova Ekaterina , Pisarev Andrei , Blagov Maxim , Samsonova Maria , Reinitz John
Published: April 2004

Motivation: To create a spatiotemporal atlas of Drosophila segmentation gene expression at cellular resolution.

Results: The expression of segmentation genes plays a crucial role in the establishment of the Drosophila body plan. Using the IBM DB2 Relational Database Management System we have designed and implemented the FlyEx database. FlyEx contains 2832 images of 14 segmentation gene expression patterns obtained from 954 embryos and 2 073 662 quantitative data records. The averaged data is available for most of segmentation genes at eight time points. FlyEx supports operations on images of gene expression patterns. The database can be used to examine the quality of data, analyze the dynamics of formation of segmentation gene expression domains, as well as estimate the variability of gene expression patterns. We also provide the capability to download data of interest.

Availability:  http://urchin.spbcas.ru/flyex, http://flyex.ams.sunysb.edu/flyex
SPrCY: comparison of structural predictions in the Saccharomyces cerevisiae genome
Authors: Dolinsky T. J. , Burgers P. M. J. , Karplus K. , Baker N. A.
Published: April 2004

Summary: SPrCY is a web-accessible database which provides comparison of structure prediction results for the Saccharomyces cerevisiae genome. This web service offers the ability to search, analyze and compare the yeast structural predictions from sequence-only (Superfamily, PDBAA BLAST and Pfam) and sequence-structure-based (SAM-T02, 3D-PSSM, mGenTHREADER) methods.

Availability: The service is freely available via web at http://agave.wustl.edu/yeast/
PedSplit: pedigree management for stratified analysis
Authors: Lanktree M. B. , VanderBeek L. , Macciardi F. M. , Kennedy J. L.
Published: April 2004

Summary: PedSplit facilitates pedigree management for gene–gene interaction and sex specific tests for increased homogeneity within subgroups. PedSplit also provides a simple approach for calculating haplotype relative risk and generating internal ‘controls’.

Availability: Executables, C++ source code and documentation for PedSplit can be downloaded from http://www.pharmacogenetics.ca in the links and software section.
BioMercator: integrating genetic maps and QTL towards discovery of candidate genes
Authors: Arcade Anne , Labourdette Aymeric , Falque Matthieu , Mangin Brigitte , Chardon Fabien , Charcosset Alain , Joets Johann
Published: April 2004

Summary: Breeding programs face the challenge of integrating information from genomics and from quantitative trait loci (QTL) analysis in order to identify genomic sequences controlling the variation of important traits. Despite the development of integrative databases, building a consensus map of genes, QTL and other loci gathered from multiple maps remains a manual and tedious task. Nevertheless, this is a critical step to reveal co-locations between genes and QTL. Another important matter is to determine whether QTL linked to same traits or related ones is detected in independent experiments and located in the same region, and represents a single locus or not. Statistical tools such as meta-analysis can be used to answer this question. BioMercator has been developed to automate map compilation and QTL meta-analysis, and to visualize co-locations between genes and QTL through a graphical interface.

Availability: Available upon request (http://moulon/~bioinfo/BioMercator/). Free of charge for academic use.
Arby: automatic protein structure prediction using profile–profile alignment and confidence measures
Authors: von Öhsen Niklas , Sommer Ingolf , Zimmer Ralf , Lengauer Thomas
Published: April 2004

Motivation: Arby is a new server for protein structure prediction that combines several homology-based methods for predicting the three-dimensional structure of a protein, given its sequence. The methods used include a threading approach, which makes use of structural information, and a profile–profile alignment approach that incorporates secondary structure predictions. The combination of the different methods with the help of empirically derived confidence measures affords reliable template selection.

Results: According to the recent CAFASP3 experiment, the server is one of the most sensitive methods for predicting the structure of single domain proteins. The quality of template selection is assessed using a fold-recognition experiment.

Availability: The Arby server is available through the portal of the Helmholtz Network for Bioinformatics at http://www.hnbioinfo.de under the protein structure category.
TRMP: a database of therapeutically relevant multiple pathways
Authors: Zheng C. J. , Zhou H. , Xie B. , Han L. Y. , Yap C. W. , Chen Y. Z.
Published: April 2004

Summary: Disease processes often involve crosstalks between proteins in different pathways. Different proteins have been used as separate therapeutic targets for the same disease. Synergetic targeting of multiple targets has been explored in combination therapy of a number of diseases. Potential harmful interactions of multiple targeting have also been closely studied. To facilitate mechanistic study of drug actions and a more comprehensive understanding the relationship between different targets of the same disease, it is useful to develop a database of known therapeutically relevant multiple pathways (TRMPs). Information about non-target proteins and natural small molecules involved in these pathways also provides useful hint for searching new therapeutic targets and facilitate the understanding of how therapeutic targets interact with other molecules in performing specific tasks. The TRMPs database is designed to provide information about such multiple pathways along with related therapeutic targets, corresponding drugs/ligands, targeted disease conditions, constituent individual pathways, structural and functional information about each protein in the pathways. Cross links to other databases are also introduced to facilitate the access of information about individual pathways and proteins.

Availability: This database can be accessed at http://bidd.nus.edu.sg/group/trmp/trmp.asp and it currently contains 11 entries of multiple pathways, 97 entries of individual pathways, 120 targets covering 72 disease conditions together with 120 sets of drugs directed at each of these targets. Each entry can be retrieved through multiple methods including multiple pathway name, individual pathway name and disease name.

Supplementary information:  http://bidd.nus.edu.sg/group/trmp/sm.pdf
Estimating and comparing the rates of gene discovery and expressed sequence tag (EST) frequencies in EST surveys
Authors: Susko Edward , Roger Andrew J.
Published: April 2004

Motivation: Expressed sequence tag (EST) surveys are an efficient way to characterize large numbers of genes from an organism. The rate of gene discovery in an EST survey depends on the degree of redundancy of the cDNA libraries from which sequences are obtained. However, few statistical methods have been developed to assess and compare redundancies of various libraries from preliminary EST surveys.

Results: We consider statistics for the comparison of EST libraries based upon the frequencies with which genes occur in subsamples of reads. These measures are useful in determining which one of several libraries is more likely to yield new genes in future reads and what proportion of additional reads one might want to take from the libraries in order to be likely to obtain new genes. One approach is to compare single sample measures that have been successfully used in species estimation problems, such as coverage of a library, defined as the proportion of the library that is represented in the given sample of reads. Another single library measure is an estimate of the expected number of additional genes that will be found in a new sample of reads. We also propose statistics that jointly use data from all the libraries. Analogous formulas for coverage and the expected numbers of new genes are presented. These measures consider coverage in a single library based upon reads from all libraries and similarly, the expected numbers of new genes that will be discovered by taking reads from all libraries with fixed proportions. Together, the statistics presented provide useful comparative measures for the libraries that can be used to guide sampling from each of the libraries to maximize the rate of gene discovery.

Finally, we present tests for whether genes are equally represented or expressed in a set of libraries. Binomial and χ2 tests are presented for gene-by-gene comparisons of expression. Overall tests of the equality of proportional representation are presented and multiple comparisons issues are addressed. These methods can be used to evaluate changes in gene expression reflected in the composition of EST libraries prepared from different tissue types or cells exposed to different environmental conditions.

Availability: Software will be made available at http://www.mathstat.dal.ca/~tsusko
The pioneer translation initiation complex is functionally distinct from but structurally overlaps with the steady-state translation initiation complex
Authors: Chiu Shang-Yi , Lejeune Fabrice , Ranganathan Aparna C. , Maquat Lynne E.
Published: April 2004

The bulk of cellular proteins derive from the translation of eukaryotic translation initiation factor (eIF)4E-bound mRNA. However, recent studies of nonsense-mediated mRNA decay (NMD) indicate that cap-binding protein (CBP)80-bound mRNA, which is a precursor to eIF4E-bound mRNA, can also be translated during a pioneer round of translation. Here, we report that the pioneer round, which can be assessed by measuring NMD, is not inhibited by 4E-BP1, which is known to inhibit steady-state translation by competing with eIF4G for binding to eIF4E. Therefore, at least in this way, the pioneer round of translation is distinct from steady-state translation. eIF4GI, poly(A)-binding protein (PABP)1, eIF3, eIF4AI, and eIF2α coimmunopurify with both CBP80 and eIF4E, which suggests that each factor functions in both modes of translation. Consistent with roles for PABP1 and eIF2α in the pioneer round of translation, PABP-interacting protein 2, which is known to destabilize PABP1 binding to poly(A) and inhibit steady-state translation, as well as inactive eIF2α, which is also known to inhibit steady-state translation, also inhibit NMD. Polysome profiles indicate that CBP80-bound mRNAs are translated less efficiently than their eIF4E-bound counterparts.
Identity work in the transition from manager to management academic
Authors: Blenkinsopp John , Stalker Brenda
Published: April 2004

The phenomenon of current practitioners moving into academia is generally welcomed in terms addressing recruitment problems and the perceived benefit of bringing practical experience into the academic setting. Yet the individual practitioner may encounter considerable difficulties with this career transition. This paper identifies the different sources and discourses of credibility – management experience versus academic knowledge – as particularly relevant, and considers the ways in which these “emergent management academics” manage their self‐identities in their day‐to‐day interactions.
The usefulness of management education
Authors: Marrington Penelope , Rowe James
Published: April 2004

This paper explores the structure and role of management education in teaching and learning management with reference to the structure (hierarchy) and control of the education process. The paper also attempts to question our fear and desire to learn and our fear and desire for learners with reference to the usefulness of management education.
Is management education beneficial to society?
Authors: Emiliani M.L.
Published: April 2004

This paper examines whether or not US‐style management education is beneficial to society and presents a review of recent events, which suggest that management education must be improved. Two principal approaches to management education and resulting practice are presented and framed differently to better reflect and comprehend societal impacts. They are termed high waste and low waste, where waste is defined as activities and behaviors that do not add value and can be eliminated. High waste management practice, or conventional management, is what the majority business schools teach. Low waste management practice, rooted in the principles and practices of the Toyota Management System, is much less common in business school education. Proposes three improvements to management education that will deliver greater benefits to society while simultaneously promoting the interests of business.
Does the talk affect your decision to walk
Authors: Brunetto Yvonne , Farr‐Wharton Rod
Published: April 2004

There is an assumption that the implementation of managerialism within public sector organisations has improved the efficiency and effectiveness of their management of processes and the outcome achieved. The aim of this pilot study was to compare the impact of changes post managerialism to organisational processes on outcomes for different types of employees. The findings suggest that the implementation of managerialism within the Australian public sector organisation has been significantly different depending on the type of employee examined. The implications for management in general are that most of the outcomes were counterintuitive and further research is required to examine the impact of the implementation of managerialism within different types of public sector organisations.
A new paradigm for business education
Authors: van der Colff Linda
Published: April 2004

As more and more organisations need not only be competitive in their internal markets, but need to be globally competitive, these economic changes impact on the content and context within which business education takes place. Company changes in the new millennium will impact on educational institutions, especially the traditional role of the business educator. As an example, due to the nature of companies becoming more and more information sensitive, managers and leaders alike need to enhance their oral and written communication skills. The pace of change within the economy as a whole is asking of managers and leaders alike to become more flexible and progressive in their management style, including developing entrepreneurial and innovation skills. Especially in the South African environment, it is important for leaders to realise the incredible potential in valuing the diverse perspective and talent of each person. The leader of the future has to learn to assist people of divergent values, beliefs and backgrounds and to weave all employees’ efforts into ultimately benefiting each individual and the organisation as a whole. Hence, what managers must be able to do in future will have a direct impact on what is needed in management education.
Teaching management and management educators: some considerations
Authors: Carneiro Alberto
Published: April 2004

This paper is concerned with some aspects of management education and intends to discuss the relationships among universities, teaching techniques, management educators, and information and communication technologies. Adopting an adequate perspective of the relationship between universities and enterprises for improving and updating management higher education, it defends that management can be taught in a better way if universities are able to explore its teachers' skills and establish very frequent partnerships with enterprises to create an environment where management activities may be better understood. The aim is to revise different issues, to emphasise the value of practical approaches of management education, the importance of pedagogy based on solving problems and the decision‐making process. An interpretative model for management education supported by the integration of management teaching techniques is presented. The model is divided into three areas: the area of theoretical resources, the area related to educator's personal experience, and a set of practical aspects where partnerships are included. Further empirical work will be required to appreciate university's committees' opinions, managerial implications, and to evaluate their statistical meaning.
Unlearning gender blindness: new directions in management education
Authors: Mavin S. , Bryans P. , Waring T.
Published: April 2004

This paper argues that business and management schools continue to operate a gender blind approach (or at best gender neutral) to management education, management research and the development of management theory. This echoes a pattern repeated in the practice of management, which closes down and inhibits opportunities for management to be “done differently” and for organisations to be different. Reflecting on the author's experiences within two business schools and on their empirical research carried out over six years, the paper provides substantive arguments for the authors' position relating to the masculine nature of management, the place of academic women in management, the male dominated processes of management education and management research and the need to place gender on the agenda in management education. The paper concludes with a call for an “unlearning” and a “rethinking” of gender blind management education and provides some examples of how this might be achieved.
Disturbing the sounds of silence – hearing other voices
Authors: Hiley Tricia
Published: April 2004

This paper explores the discipline, study and practice of management through the “current voice of management” and through four different voices. The four different voices are those of: a one‐person business, a PhD researcher in a school of management, a co‐ordinator of an articulated inter‐disciplinary Masters program in the Leadership and Management of Change, and a management consultant. The paper first introduces some implications of our current management voices and then explores aspects of each voice, concluding with a short reflection on the message drawn from them.
Can management be taught?
Authors: Elmuti Dean
Published: April 2004

The topic whether management skills are communicable has been the topic of scholars' debates and broad examination through literature in the last decades. However, there is less literature focusing on solutions for successful management education. This paper, not only takes up a position that management can be taught and learned, but also examines how the learning process is approached. The paper discusses characteristics of successful management educators and determine their impacts on management development. The paper determines the qualities and skills that modern managers must develop, especially in this time of globalization and rapid change in the business world. It suggests educating managers in “soft skills” such as interpersonal and intrapersonal skills and not merely concentrating on the “hard skills”, such as analytical skills. Additionally in this work, the need for managers with international exposure and cross‐cultural experience is emphasized. Finally, a proposal for management education curricula is tabled and address the issue of limits of management education is addresed.
Person‐organization value congruence, burnout and diversion of resources
Authors: Siegall Marc , McDonald Tracy
Published: April 2004

One‐hundred‐thirty‐five university faculties participated in a survey‐based study of burnout. This study investigated the role of person‐organization value congruence on the experience of burnout. Also, the mediating role of burnout on the relationship between person‐organization value congruence and outcomes (in congruence with Maslach, Schaufel and Leiter's theory) was examined. As predicted by a coping/withdrawal framework, burnout was associated with less time spent on teaching, service/administrative tasks, and professional development activities. To a lesser extent, burnout was associated with spending more time on non‐work activities. Person‐organization value congruence was strongly associated with burnout. Value congruence had direct relationships with several of the outcome variables, and, consistent with the model, burnout partially or fully mediated the relationship between congruence and satisfaction, spending less time on teaching, and on professional development activities.
Profit sharing, firm performance and union influence in selected European countries
Authors: D'Art Daryl , Turner Thomas
Published: April 2004

Schemes of profit sharing and employee share‐holding have a 19th century origin. The objects of profit sharing vary according to its proponents. The primary focus of this paper will be on managerial schemes of financial participation and the expectations that their installation will lead to an improvement in organizational performance and employee behaviour. Using a survey of 2,827 private sector firms in 11 European countries we test for the effect of profit sharing on profitability, productivity and employee turnover and absenteeism. In addition, the effect of profit sharing on union influence is examined. In common, with other research in this area, our results show that while there is some evidence of a positive relationship between profit sharing and organizational performance, this was not definitive. In the case of union influence, there was some evidence of an adverse effect of these schemes on the solidarity of the collective.
Micro and modular assembly approaches headline fall shows
Authors: Bloss Richard
Published: April 2004

Automated assembly is moving to smaller and more flexible systems and components, offering greater ability for redeployment and adaptability to device assembly as small as micro electromechanical systems.
Interactive motion control using Ch – an embeddable C/C++ interpreter
Authors: Nestinger Stephen S. , Cheng Harry H.
Published: April 2004

A flexible agile assembly system requires an open architecture integration environment that is mechatronic device and computer platform independent. An interactive environment allows the users to step through programs and acquire immediate feedback from the system and is most suitable for the development of mechatronic systems used on the shop floor. Ch, an embeddable C/C++ interpreter, was developed for mechatronic‐independent task‐level programming. An experimental mechatronic system with an IBM 7575 Robotic Arm and a National Instruments' motion control board has been developed to demonstrate the capabilities and the ease in integrating mechatronic devices in Ch, which is freely available for downloading.
A new level of automation in fraction HP (kW) electric motor manufacturing
Authors: Kirkhoff Jim
Published: April 2004

A new innovative automated assembly system produces a wide range of fractional horsepower (kilowatt ) motor stators in a flex‐flow configuration for minimum change over time.
A real‐time manufacturing/assembly system performance evaluation and control model with integrated sensory feedback processing and visualization
Authors: Ranky Paul G.
Published: April 2004

The aim of this paper is to introduce a real‐time performance evaluation and control model, for the purpose of reducing cost and improving the quality, and the real‐time responsiveness of manufacturing/assembly systems and enterprises that host them. In order to make the approach practical, networking solutions with integrated sensory feedback processing and visualization methods are illustrated. In this paper we summarize the core concepts of our method and demonstrate some quality industrial solutions.
A force‐reflecting teleoperator system with assembly state feedback
Authors: Lau H.Y.K. , Ngan M.C.C. , Wai L.C.C. , Ng A.K.S.
Published: April 2004

The ability to appreciate the sensation of force and torque that is experienced by the slave device in a teleoperator system is essential for achieving remote manipulations such as assembly and disassembly, telesurgery, and remote handling of delicate and dangerous substances. This paper describes an intelligent teleoperator system that not only provides high quality force feedback information in teleoperation but also additional information about the contact formation between the slave device and the environment is presented to the operator. This paper also discusses the design of the teleoperator system and introduces its architecture. Experimental study using the developed teleoperator system is presented that highlights its performance in real life applications.