bluuebunny/crossref_metadata_2025 huggingface dataset:
H2AX regulates meiotic telomere clustering
Authors: Fernandez-Capetillo Oscar , Liebe Bodo , Scherthan Harry , Nussenzweig André
Published: October 2003

The histone H2A variant H2AX is phosphorylated in response to DNA double-strand breaks originating from diverse origins, including dysfunctional telomeres. Here, we show that normal mitotic telomere maintenance does not require H2AX. Moreover, H2AX is dispensable for the chromosome fusions arising from either critically shortened or deprotected telomeres. However, H2AX has an essential role in controlling the proper topological distribution of telomeres during meiotic prophase I. Our results suggest that H2AX is a downstream effector of the ataxia telangiectasia–mutated kinase in controlling telomere movement during meiosis.
Route of Immunization with Peptide-pulsed Dendritic Cells Controls the Distribution of Memory and Effector T Cells in Lymphoid Tissues and Determines the Pattern of Regional Tumor Control
Authors: Mullins David W. , Sheasley Stacey L. , Ream Rebecca M. , Bullock Timothy N.J. , Fu Yang-Xin , Engelhard Victor H.
Published: October 2003

We have established that the route of immunization with peptide-pulsed, activated DC leads to memory CD8+ T cells with distinct distributions in lymphoid tissues, which determines the ability to control tumors growing in different body sites. Both intravenous (i.v.) and subcutaneous (s.c.) immunization induced memory T cells in spleen and control of metastatic-like lung tumors. s.c. immunization also induced memory T cells in lymph nodes (LNs), imparting protection against subcutaneously growing tumors. In contrast, i.v. immunization-induced memory was restricted to spleen and failed to impart protective immunity against subcutaneously growing tumors. Memory cell distribution and tumor control were both linked to injection route–dependent localization of DCs in lymphoid compartments. Using peripheral LN–ablated mice, these LNs were shown to be essential for control of subcutaneously growing tumors but not lung metastases; in contrast, using immunized asplenic mice, we found that the spleen is necessary and sufficient for control of lung tumors, but unnecessary for control of subcutaneously growing tumors. These data demonstrate the existence of a previously undescribed population of splenic-resident memory CD8 T cells that are essential for the control of lung metastases. Thus, regional immunity based on memory T cell residence patterns is an important factor in DC-based tumor immunotherapy.
Targeting Platelet–Leukocyte Interactions
Authors: Ehlers Raila , Ustinov Valentin , Chen Zhiping , Zhang Xiaobin , Rao Ravi , Luscinskas F. William , Lopez Jose , Plow Edward , Simon Daniel I.
Published: October 2003

The firm adhesion and transplatelet migration of leukocytes on vascular thrombus are dependent on the interaction of the leukocyte integrin Mac-1 (αMβ2, CD11b/CD18) and the platelet counter receptor glycoprotein (GP) Ibα. Previous studies have established a central role for the I domain, a stretch of ∼200 amino acids within the αM subunit, in the binding of GP Ibα. This study was undertaken to establish the molecular basis of GP Ibα recognition by αMβ2. The P201–K217 sequence, which spans an exposed loop and amphipathic α4 helix in the three-dimensional structure of the αMI domain, was identified as the binding site for GP Ibα. Mutant cell lines in which the αMI domain segments P201–G207 and R208–K217 were switched to the homologous, but non-GP Ibα binding, αL domain segments failed to support adhesion to GP Ibα. Mutation of amino acid residues within P201–K217, H210–A212, T213–I215, and R216–K217 resulted in the loss of the binding function of the recombinant αMI domains to GP Ibα. Synthetic peptides duplicating the P201–K217, but not scrambled versions, directly bound GP Ibα and inhibited αMβ2-dependent adhesion to GP Ibα and adherent platelets. Finally, grafting critical amino acids within the P201–K217 sequence onto αL, converted αLβ2 into a GP Ibα binding integrin. Thus, the P201–K217 sequence within the αMI domain is necessary and sufficient for GP Ibα binding. These observations provide a molecular target for disrupting leukocyte–platelet complexes that promote vascular inflammation in thrombosis, atherosclerosis, and angioplasty-related restenosis.
Antiadhesive Role of Apical Decay-accelerating Factor (CD55) in Human Neutrophil Transmigration across Mucosal Epithelia
Authors: Lawrence Donald W. , Bruyninckx Walter J. , Louis Nancy A. , Lublin Douglas M. , Stahl Gregory L. , Parkos Charles A. , Colgan Sean P.
Published: October 2003

Neutrophil migration across mucosal epithelium during inflammatory episodes involves the precise orchestration of a number a cell surface molecules and signaling pathways. After successful migration to the apical epithelial surface, apically localized epithelial proteins may serve to retain PMN at the lumenal surface. At present, identification of apical epithelial ligands and their PMN counter-receptors remain elusive. Therefore, to define the existence of apical epithelial cell surface proteins involved in PMN–epithelial interactions, we screened a panel of antibodies directed against epithelial plasma membranes. This strategy identified one antibody (OE-1) that both localized to the apical cell membrane and significantly inhibited PMN transmigration across epithelial monolayers. Microsequence analysis revealed that OE-1 recognized human decay-accelerating factor (DAF, CD55). DAF is a highly glycosylated, 70–80-kD, glycosyl-phosphatidyinositol–linked protein that functions predominantly as an inhibitor of autologous complement lysis. DAF suppression experiments using antisense oligonucleotides or RNA interference revealed that DAF may function as an antiadhesive molecule promoting the release of PMN from the lumenal surface after transmigration. Similarly, peptides corresponding to the antigen recognition domain of OE-1 resulted in accumulation of PMN on the apical epithelial surface. The elucidation of DAF as an apical epithelial ligand for PMN provides a target for novel anti-inflammatory therapies directed at quelling unwanted inflammatory episodes.
Specific Recruitment of Antigen-presenting Cells by Chemerin, a Novel Processed Ligand from Human Inflammatory Fluids
Authors: Wittamer Valérie , Franssen Jean-Denis , Vulcano Marisa , Mirjolet Jean-François , Le Poul Emmanuel , Migeotte Isabelle , Brézillon Stéphane , Tyldesley Richard , Blanpain Cédric , Detheux Michel , Mantovani Alberto , Sozzani Silvano , Vassart Gilbert , Parmentier Marc , Communi David
Published: October 2003

Dendritic cells (DCs) and macrophages are professional antigen-presenting cells (APCs) that play key roles in both innate and adaptive immunity. ChemR23 is an orphan G protein–coupled receptor related to chemokine receptors, which is expressed specifically in these cell types. Here we present the characterization of chemerin, a novel chemoattractant protein, which acts through ChemR23 and is abundant in a diverse set of human inflammatory fluids. Chemerin is secreted as a precursor of low biological activity, which upon proteolytic cleavage of its COOH-terminal domain, is converted into a potent and highly specific agonist of ChemR23, the chemerin receptor. Activation of chemerin receptor results in intracellular calcium release, inhibition of cAMP accumulation, and phosphorylation of p42–p44 MAP kinases, through the Gi class of heterotrimeric G proteins. Chemerin is structurally and evolutionary related to the cathelicidin precursors (antibacterial peptides), cystatins (cysteine protease inhibitors), and kininogens. Chemerin was shown to promote calcium mobilization and chemotaxis of immature DCs and macrophages in a ChemR23-dependent manner. Therefore, chemerin appears as a potent chemoattractant protein of a novel class, which requires proteolytic activation and is specific for APCs.
Constitutive Cytokine mRNAs Mark Natural Killer (NK) and NK T Cells Poised for Rapid Effector Function
Authors: Stetson Daniel B. , Mohrs Markus , Reinhardt R. Lee , Baron Jody L. , Wang Zhi-En , Gapin Laurent , Kronenberg Mitchell , Locksley Richard M.
Published: October 2003

Natural killer (NK) and NK T cells are tissue lymphocytes that secrete cytokines rapidly upon stimulation. Here, we show that these cells maintain distinct patterns of constitutive cytokine mRNAs. Unlike conventional T cells, NK T cells activate interleukin (IL)-4 and interferon (IFN)-γ transcription during thymic development and populate the periphery with both cytokine loci previously modified by histone acetylation. Similarly, NK cells transcribe and modify the IFN-γ gene, but not IL-4, during developmental maturation in the bone marrow. Lineage-specific patterns of cytokine transcripts predate infection and suggest evolutionary selection for invariant but distinct types of effector responses among the earliest responding lymphocytes.
Effective Destruction of Fas-deficient Insulin-producing β Cells in Type 1 Diabetes
Authors: Apostolou Irina , Hao Zhenyue , Rajewsky Klaus , von Boehmer Harald
Published: October 2003

In type 1 diabetes, autoimmune T cells cause destruction of pancreatic β cells by largely unknown mechanism. Previous analyses have shown that β cell destruction is delayed but can occur in perforin-deficient nonobese diabetic (NOD) mice and that Fas-deficient NOD mice do not develop diabetes. However, because of possible pleiotropic functions of Fas, it was not clear whether the Fas receptor was an essential mediator of β cell death in type 1 diabetes. To directly test this hypothesis, we have generated a β cell–specific knockout of the Fas gene in a transgenic model of type 1 autoimmune diabetes in which CD4+ T cells with a transgenic TCR specific for influenza hemagglutinin (HA) are causing diabetes in mice that express HA under control of the rat insulin promoter. Here we show that the Fas-deficient mice develop autoimmune diabetes with slightly accelerated kinetics indicating that Fas-dependent apoptosis of β cells is a dispensable mode of cell death in this disease.
The Strength of Persistent Antigenic Stimulation Modulates Adaptive Tolerance in Peripheral CD4+ T Cells
Authors: Singh Nevil J. , Schwartz Ronald H.
Published: October 2003

The quantitative adaptation of receptor thresholds allows cells to tailor their responses to changes in ambient ligand concentration in many biological systems. Such a cell-intrinsic calibration of T cell receptor (TCR) sensitivity could be involved in regulating responses to autoantigens, but this has never been demonstrated for peripheral T cells. We examined the ability of monoclonal naive T cells to modulate their responsiveness differentially after exposure to fourfold different levels of persistent antigen stimulation in vivo. T cells expanded and entered a tolerant state with different kinetics in response to the two levels of stimulation, but eventually adjusted to a similar slow rate of turnover. In vivo restimulation revealed a greater impairment in the proliferative ability of T cells resident in a higher antigen presentation environment. We also observed subtle differences in TCR signaling and in vitro cytokine production consistent with differential adaptation. Unexpectedly, the system failed to similarly compensate to the persistent stimulus in vivo at the level of CD69 expression and actin polymerization. This greater responsiveness of T cells residing in a host with a lower level of antigen presentation allows us to demonstrate for the first time an intrinsic tuning process in mature T lymphocytes, albeit one more complex than current theories predict.
Reprographic rights in Singapore: the story of CLASS
Authors: Davison Peter
Published: October 2003

The Copyright Licensing and Administration Society of Singapore was established in 1999. It is now profitable and commercially significant, perhaps uniquely so in Asia. Critical factors in its growth have included a statutory (non‐voluntary) photocopying licence provision for educational institutions in the Copyright Act; and widespread support from the local and international communities of rightsholders. Tentative consensus has been established with educators over a fair level of remuneration for copying. Further work needs to be done to extend or amend the current model for electronic copying, for the private sector and for other countries in the region.
Post‐publication filtering and evaluation: Faculty of 1000
Authors: Wets Kathleen , Weedon Dave , Velterop Jan
Published: October 2003

Faculty of 1000 (www.facultyof1000.com) is a new on‐line literature awareness and assessment service of research papers, on the basis of selections by 1400 of the world's top biologists, that combines metrics with judgement. The service offers a systematic and comprehensive form of post‐publication peer review that focuses on the best papers regardless of the journal in which they are published. It is now possible to draw some conclusions about how this new form of post‐publication peer review meets the needs of scientists, and the organizations that fund them, in practice. In addition, inferences about the relative importance of journals are set out, which should also interest publishers and librarians.
Publication in foreign journals and promotion of academics in Nigeria
Authors: Adomi Esharenana E. , Mordi Chinedum
Published: October 2003

The emphasis placed on articles in foreign journals in the assessment of academics for senior posts in Nigerian universities is described and the policies involved are discussed and their consequences assessed.
Alternative futures for academic and professional publishing
Authors: Dryburgh Alastair
Published: October 2003

The article examines the future of academic and professional publishing by proposing four generic models which, possibly in combination with each other, represent any possible publishing activity. It examines the factors encouraging or impeding development of each model and the ways in which publishers could make transitions from one to another.
Organization and technology for the recording of science
Authors: Lindquist Mats G.
Published: October 2003

Scientific research requires access to earlier research results. Over time a system supporting scientific exchange has evolved where publishers, libraries and archives each have well‐defined institutional roles. New information and communication technologies are challenging the established order for the recording of science and alternative systems are evolving. A strong commercial market for STI coupled with decreased purchasing power on the part of libraries makes organizational issues as important as technological ones.
Googled: the quest for visibility on the Internet
Authors: Beckwith Kimberly
Published: October 2003

Small publishing‐related firms have a problem getting their services and products known to the scholarly and STM market. Getting listed on search engine results pages is difficult due to the way the most popular search engines rank sites. Galayaa has tried out Google's AdWords as a way to get noticed. Does it work? An impression of early results of the campaign is given.
Of wolves and and boys: the scholarly communication crisis
Authors: Tananbaum Greg
Published: October 2003

The case for the self‐publishing by academic institutions of scholarly research as a response to the 'serials crisis' is made against the background of the experience of Bepress. It is suggested that such arrangements provide a valuable and cost‐effective answer to the problem.
What does ZWOLLE stand for?
Authors: Harvey Judith
Published: October 2003

Zwolle stands for a unique approach to the management of copyright in international higher and further education. The stakeholders in copyright management include authors, publishers, librarians, universities and the public. The seven Zwolle Principles were agreed at the conference on Copyright and Universities held in Zwolle in The Netherlands in December 2002. The principles and the examples of good practice in copyright management represent the best opportunity for resolving differences and achieving convergence of the interests of stakeholders.
RoMEO studies 4: an analysis of journal publishers' copyright agreements
Authors: Gadd Elizabeth , Oppenheim Charles , Probets Steve
Published: October 2003

This article is the fourth in a series of six emanating from the UK JISC‐funded RoMEO Project (Rights Metadata for Open archiving). It describes an analysis of 80 scholarly journal publishers' copyright agreements with a particular view to their effect on author self‐archiving: 90% of agreements asked for copyright transfer and 69% asked for it prior to refereeing the paper; 75% asked authors to warrant that their work had not been previously published although only two explicitly stated that they viewed self‐archiving as prior publication; 28.5% of agreements provided authors with no usage rights over their own paper. Although 42.5% allowed self‐archiving in some format, there was no consensus on the conditions under which self‐archiving could take place. The article concludes that author–publisher copyright agreements should be reconsidered by a working party representing the needs of both parties.
Book Reviews
Authors: Robson Jodie , Blackburn Cathleen
Published: October 2003

The Accidental Webmaster by Julie M. Still Information Today, 2003. Pp 192. Paperback $29.50. ISBN 1‐57387‐164‐8

Clark's Publishing Agreements – A Book of Precedents, 6th edn, General Editor Lynette Owen

Butterworths Lexis Nexis, 2002, £70.85. 615 pp. Hardback and CD‐ROM. ISBN 0‐406‐93916‐0
A Novel Cytoplasmic Tail MXXXL Motif Mediates the Internalization of Prostate-specific Membrane Antigen
Authors: Rajasekaran Sigrid A. , Anilkumar Gopalakrishnapillai , Oshima Eri , Bowie James U. , Liu He , Heston Warren , Bander Neil H. , Rajasekaran Ayyappan K.
Published: October 2003

Prostate-specific membrane antigen (PSMA) is a transmembrane protein expressed at high levels in prostate cancer and in tumor-associated neovasculature. In this study, we report that PSMA is internalized via a clathrin-dependent endocytic mechanism and that internalization of PSMA is mediated by the five N-terminal amino acids (MWNLL) present in its cytoplasmic tail. Deletion of the cytoplasmic tail abolished PSMA internalization. Mutagenesis of N-terminal amino acid residues at position 2, 3, or 4 to alanine did not affect internalization of PSMA, whereas mutation of amino acid residues 1 or 5 to alanine strongly inhibited internalization. Using a chimeric protein composed of Tac antigen, the α-chain of interleukin 2-receptor, fused to the first five amino acids of PSMA (Tac-MWNLL), we found that this sequence is sufficient for PSMA internalization. In addition, inclusion of additional alanines into the MWNLL sequence either in the Tac chimera or the full-length PSMA strongly inhibited internalization. From these results, we suggest that a novel MXXXL motif in the cytoplasmic tail mediates PSMA internalization. We also show that dominant negative μ2 of the adaptor protein (AP)-2 complex strongly inhibits the internalization of PSMA, indicating that AP-2 is involved in the internalization of PSMA mediated by the MXXXL motif.
Targeting of a Tropomyosin Isoform to Short Microfilaments Associated with the Golgi Complex
Authors: Percival Justin M. , Hughes Julie A. I. , Brown Darren L. , Schevzov Galina , Heimann Kirsten , Vrhovski Bernadette , Bryce Nicole , Stow Jennifer L. , Gunning Peter W.
Published: October 2003

A growing body of evidence suggests that the Golgi complex contains an actin-based filament system. We have previously reported that one or more isoforms from the tropomyosin gene Tm5NM (also known as γ-Tm), but not from either the α- or β-Tm genes, are associated with Golgi-derived vesicles (Heimann et al., ( 1999 ). J. Biol. Chem. 274, 10743-10750). We now show that Tm5NM-2 is sorted specifically to the Golgi complex, whereas Tm5NM-1, which differs by a single alternatively spliced internal exon, is incorporated into stress fibers. Tm5NM-2 is localized to the Golgi complex consistently throughout the G1 phase of the cell cycle and it associates with Golgi membranes in a brefeldin A-sensitive and cytochalasin D-resistant manner. An actin antibody, which preferentially reacts with the ends of microfilaments, newly reveals a population of short actin filaments associated with the Golgi complex and particularly with Golgi-derived vesicles. Tm5NM-2 is also found on these short microfilaments. We conclude that an alternative splice choice can restrict the sorting of a tropomyosin isoform to short actin filaments associated with Golgi-derived vesicles. Our evidence points to a role for these Golgi-associated microfilaments in vesicle budding at the level of the Golgi complex.
Direct Binding of the Ligand PSG17 to CD9 Requires a CD9 Site Essential for Sperm-Egg Fusion
Authors: Ellerman Diego A. , Ha Cam , Primakoff Paul , Myles Diana G. , Dveksler Gabriela S.
Published: October 2003

The function currently attributed to tetraspanins is to organize molecular complexes in the plasma membrane by using multiple cis-interactions. Additionally, the tetraspanin CD9 may be a receptor that binds the soluble ligand PSG17, a member of the immunoglobulin superfamily (IgSF)/CEA subfamily. However, previous data are also consistent with the PSG17 receptor being a CD9 cis-associated protein. In the current study, CD9 extracellular loop (EC2) specifically bound to PSG17-coated beads, indicating a direct interaction between the two proteins. However, CD9-EC2 did not bind to PSG17-coated beads if the CD9-EC2 had the mutation SFQ (173-175) to AAA, a previously studied mutation in egg CD9 that abolishes sperm-egg fusion. Also, PSG17 bound to 293 T cells transfected with wild-type CD9 but not the mutant CD9. By immunofluorescence, PSG17 bound to wild-type eggs but not to CD9 null eggs. The presence of ∼2 μM recombinant PSG17 produced a significant and reversible inhibition (60-80%) of sperm-egg fusion. Thus, we conclude that CD9 is a receptor for PSG17 and when the PSG17 binding site is mutated or occupied, sperm-egg fusion is impaired. These findings suggest that egg CD9 may function in gamete fusion by binding to a sperm IgSF/CEA subfamily member and such proteins have previously been identified on sperm.
Synaptophysin I Controls the Targeting of VAMP2/Synaptobrevin II to Synaptic Vesicles
Authors: Pennuto Maria , Bonanomi Dario , Benfenati Fabio , Valtorta Flavia
Published: October 2003

Synaptic vesicle (SV) proteins are synthesized at the level of the cell body and transported down the axon in membrane precursors of SVs. To investigate the mechanisms underlying sorting of proteins to SVs, fluorescent chimeras of vesicle-associated membrane protein (VAMP) 2, its highly homologous isoform VAMP1 and synaptotagmin I (SytI) were expressed in hippocampal neurons in culture. Interestingly, the proteins displayed a diffuse component of distribution along the axon. In addition, VAMP2 was found to travel in vesicles that constitutively fuse with the plasma membrane. Coexpression of VAMP2 with synaptophysin I (SypI), a major resident of SVs, restored the correct sorting of VAMP2 to SVs. The effect of SypI on VAMP2 sorting was dose dependent, being reversed by increasing VAMP2 expression levels, and highly specific, because the sorting of the SV proteins VAMP1 and SytI was not affected by SypI. The cytoplasmic domain of VAMP2 was found to be necessary for both the formation of VAMP2-SypI hetero-dimers and for VAMP2 sorting to SVs. These data support a role for SypI in directing the correct sorting of VAMP2 in neurons and demonstrate that a direct interaction between the two proteins is required for SypI in order to exert its effect.
The Adaptor Protein ARH Escorts Megalin to and through Endosomes
Authors: Nagai Masaaki , Meerloo Timo , Takeda Tetsuro , Farquhar Marilyn Gist
Published: October 2003

Megalin is an endocytic receptor that binds multiple ligands and is essential for many physiological processes such as brain development and uptake of proteins by the kidney tubule, yolk sac, and thyroid. The cytoplasmic tail of megalin contains two FXNPXY motifs. Autosomal recessive hypercholesterolemia (ARH) is an adaptor protein that binds to the FXNPXY motif of the low-density lipoprotein receptor as well as clathrin and AP-2. We found that ARH also binds to the first FXNPXY motif of megalin in two-hybrid, pull-down and coimmunoprecipitation assays. ARH colocalizes with megalin in clathrin coated pits and in recycling endosomes in the Golgi region. When cells are treated with nocodazole, the recycling endosomes containing megalin and ARH disperse. On internalization of megalin, ARH and megalin are first seen in clathrin coated pits followed by sequential localization in early endosomes and tubular recycling endosomes in the pericentriolar region followed by their reappearance at the cell surface. Expression of ARH in Madin-Darby canine kidney cells expressing megalin mini-receptors enhances megalin-mediated uptake of125I-lactoferrin, a megalin ligand. These results show that ARH facilitates endocytosis of megalin, escorts megalin along its endocytic route and raise the possibility that transport through the endosomal system is selective and requires interaction with specific adaptor proteins.
Scavenger Receptor BI (SR-BI) Clustered on Microvillar Extensions Suggests that This Plasma Membrane Domain Is a Way Station for Cholesterol Trafficking between Cells and High-Density Lipoprotein
Authors: Peng Yinan , Akmentin Wendy , Connelly Margery A. , Lund-Katz Sissel , Phillips Michael C. , Williams David L.
Published: October 2003

Receptor-mediated trafficking of cholesterol between lipoproteins and cells is a fundamental biological process at the organismal and cellular levels. In contrast to the well-studied pathway of LDL receptor-mediated endocytosis, little is known about the trafficking of high-density lipoprotein (HDL) cholesterol by the HDL receptor, scavenger receptor BI (SR-BI). SR-BI mediates HDL cholesteryl ester uptake in a process in which HDL lipids are selectively transferred to the cell membrane without the uptake and degradation of the HDL particle. We report here the cell surface locale where the trafficking of HDL cholesterol occurs. Fluorescence confocal microscopy showed SR-BI in patches and small extensions of the cell surface that were distinct from sites of caveolin-1 expression. Electron microscopy showed SR-BI in patches or clusters primarily on microvillar extensions of the plasma membrane. The organization of SR-BI in this manner suggests that this microvillar domain is a way station for cholesterol trafficking between HDL and cells. The types of phospholipids in this domain are unknown, but SR-BI is not strongly associated with classical membrane rafts rich in detergent-resistant saturated phospholipids. We speculate that SR-BI is in a more fluid membrane domain that will favor rapid cholesterol flux between the membrane and HDL.
Telomerase RNA Accumulates in Cajal Bodies in Human Cancer Cells
Authors: Zhu Yusheng , Tomlinson Rebecca L. , Lukowiak Andrew A. , Terns Rebecca M. , Terns Michael P.
Published: October 2003

Telomerase synthesizes telomeric DNA repeats at the ends of eukaryotic chromosomes. The RNA component of the enzyme (hTR) provides the template for telomere synthesis, which is catalyzed by telomerase reverse transcriptase (hTERT). Little is known regarding the subcellular localization of hTR and hTERT and the pathway by which telomerase is assembled. Here we report the first glimpse of the detailed subcellular localization of endogenous hTR in human cells, which we obtained by fluorescence in situ hybridization (FISH). Our studies have revealed a distinctive hTR localization pattern in cancer cells. We have found that hTR accumulates within intranuclear foci called Cajal bodies in all typical tumor-derived cell lines examined (in which telomerase is active), but not in primary or ALT cells (where little or no hTERT is present). Accumulation of hTR in the Cajal bodies of primary cells is induced when hTERT is ectopically expressed. Moreover, we report that hTERT is also found in Cajal bodies. Our data suggest that Cajal bodies are involved in the assembly and/or function of human telomerase.
STAT3-dependent enhanceosome assembly and disassembly: synergy with GR for full transcriptional increase of the α2-macroglobulin gene
Authors: Lerner Lorena , Henriksen Melissa A. , Zhang Xiaokui , Darnell James E.
Published: October 2003

We describe a detailed time course of the assembly and disassembly of a STAT3-dependent, glucocorticoid-supplemented enhanceosome for the α2-macroglobulin (α2-M) gene and compare this with a detailed time course of transcription of the gene by run-on analysis. The glucocorticoid receptor (GR) can associate with the enhanceosome without STAT3. Furthermore, the enhanceosome contains c-Jun/c-Fos and OCT-1 constitutively. All of these factors (GR, c-Jun, OCT-1) have transcription activation domains, but STAT3 is required for the observed transcriptional increase. The time course of enhanceosome occupation by GR and tyrosine-phosphorylated STAT3 shows that these transcription factors precede by ∼5-10 min the arrival of RNA polymerase II (Pol II). The enhanceosome remains assembled for ∼90 min in the continued presence of both inducers. When IL-6 and Dex are removed (after 30 min of treatment), the disappearance within an additional 30 min of the established enhanceosome indicates that renewal of STAT3 and GR binding must occur in the continued presence of IL-6+Dex. Compared with the total nuclear tyrosine-phosphorylated STAT3 capable of binding DNA, the chromatin-associated STAT3 resists dephosphorylation and appears to recycle to maintain the enhanceosome. Run-on transcription shows a lag after full enhanceosome occupation that can be largely but not completely explained by the ∼30 min transit time of Pol II across the α2-Mlocus.
Gene Loss, Protein Sequence Divergence, Gene Dispensability, Expression Level, and Interactivity Are Correlated in Eukaryotic Evolution
Authors: Krylov Dmitri M. , Wolf Yuri I. , Rogozin Igor B. , Koonin Eugene V.
Published: October 2003

Lineage-specific gene loss, to a large extent, accounts for the differences in gene repertoires between genomes, particularly among eukaryotes. We derived a parsimonious scenario ofgene losses for eukaryotic orthologous groups (KOGs) from seven complete eukaryotic genomes. The scenario involves substantial gene loss in fungi, nematodes, and insects. Based on this evolutionary scenario and estimates of the divergence times between major eukaryotic phyla, we introduce a numerical measure, the propensity for gene loss (PGL). We explore the connection among the propensity of a gene to be lost in evolution (PGL value), protein sequence divergence, the effect of gene knockout on fitness, the number of protein-protein interactions, and expression level for the genes in KOGs. Significant correlations between PGL and each of these variables were detected. Genes that have a lower propensity to be lost in eukaryotic evolution accumulate fewer substitutions in their protein sequences and tend to be essential for the organism viability, tend to be highly expressed, and have many interaction partners. The dependence between PGL and gene dispensability and interactivity is much stronger than that for sequence evolution rate. Thus, propensity of a gene to be lost during evolution seems to be a direct reflection of its biological importance.
Comprehensive Analysis of Orthologous Protein Domains Using the HOPS Database
Authors: Storm Christian E.V. , Sonnhammer Erik L.L.
Published: October 2003

One of the most reliable methods for protein function annotation is to transfer experimentally known functions from orthologous proteins in other organisms. Most methods for identifying orthologs operate on a subset of organisms with a completely sequenced genome, and treat proteins as single-domain units. However, it is well known that proteins are often made up of several independent domains, and there is a wealth of protein sequences from genomes that are not completely sequenced. A comprehensive set of protein domain families is found in the Pfam database. We wanted to apply orthology detection to Pfam families, but first some issues needed to be addressed. First, orthology detection becomes impractical and unreliable when too many species are included. Second, shorter domains contain less information. It is therefore important to assess the quality of the orthology assignment and avoid very short domains altogether. We present a database of orthologous protein domains in Pfam called HOPS: Hierarchical grouping of Orthologous and Paralogous Sequences. Orthology is inferred in a hierarchic system of phylogenetic subgroups using ortholog bootstrapping. To avoid the frequent errors stemming from horizontally transferred genes in bacteria, the analysis is presently limited to eukaryotic genes. The results are accessible in the graphical browser NIFAS, a Java tool originally developed for analyzing phylogenetic relations within Pfam families. The method was tested on a set of curated orthologs with experimentally verified function. In comparison to tree reconciliation with a complete species tree, our approach finds significantly more orthologs in the test set. Examples for investigating gene fusions and domain recombination using HOPS are given.
The impact of leader characteristics on the performance of organizational members: an exploratory study
Authors: Adeyemi‐Bello Tope
Published: October 2003

The commitment or loyalty of organizational members is one of the important determinants of leadership success. This study examines the relationship between leaders’ locus of control and value orientation to the performance of the members in a type of not‐for‐profit organization. The results indicate that leaders with conservative values and internal locus of control tend to elicit higher levels of performance from their members. The implications of these results are discussed.
Work‐related research, education and training in developing countries
Authors: Ahasan Rabiul
Published: October 2003

The rapid spread of industrialisation means that for many developing countries economic performance is sometimes regarded as such a high priority that work‐related injuries, accidents and occupational diseases are tolerated. In such countries there will be little education and training relating to ergonomics or industrial health and safety. Well‐meaning external agencies often fail to target promotional activity and training at the appropriate level or within the local cultural framework. This paper discusses reasons for this, and suggests models for co‐operative development which can ensure that social development and improved working practices go hand in hand with economic development.
Enhancing quality in education: application of quality function deployment – an industry perspective
Authors: Sahney Sangeeta , Banwet Devinder Kumar , Karunes Sabita
Published: October 2003

Education is a service industry. It needs to adopt the techniques of other industries in measuring the quality of its services and the satisfaction of its customers. This paper reports on a study of educational institutes in India in terms of how well they meet the needs of local industrial customers. It involves the use of quality function deployment, and a range of statistical techniques, to design and analyze a questionnaire which results in a clear demonstration of a lack of satisfaction. The analysis also identifies those factors which should be specifically addressed to improve quality and customer satisfaction.
A new mandate for operations managers
Authors: Aghazadeh Seyed‐Mahmoud
Published: October 2003

Labor planning is a key component of production/operations management. A productive organization needs a workforce that is of the right size, is competent and is well‐motivated. Production/operations managers need to understand the tools and techniques at their disposal to create such a workforce. This paper examines some of the key issues relating to labor planning and management, and introduces some of the available approaches and tools that can help shape and direct a workforce to productive ends.
Polish mass privatisation scheme: the legal framework
Authors: Kruczalak‐Jankowska Joanna , Kruczalak Kazimerz
Published: October 2003

The main purpose of this paper is to approach the legal problems of mass privatisation in Poland. The authors present the structure of national investment funds which intend to be the experimental financial intermediaries in Poland. Their assets are quoted on the Stock Exchange in Warsaw from the beginning of May 1997. New and controversial roles of management firms are discussed in this paper.
Corporate governance and mass privatisation
Authors: Stephen Frank H. , Backhaus Ju¨rgen G.
Published: October 2003

After the precipitated decline of the Soviet Empire and its satellite states, a system change seemed to be called for, and many countries embarked on social and political reforms focussing on property structures in the economy. This raised the issue of governance in the institutions that would constitute the structures in which production would have to take place. In particular, some Central European countries opted for mass privatisations of the means of production, on the face of it so as to have the people participate in the wealth of the nation. In fact, the wealth of the nation depends on the structures in which it is constituted. Dissipation of property rights will reduce the value of the nation's productive capital, whereas an intelligent structure that creates good governance structures at the same time, increases the value of the producing capital. This relatively simple insight lies at the heart of our understanding of how to analyse different processes of mass privatisation. This essay develops a theoretical framework by which different governance structures can be analysed. The framework consists of a blend of the economic theory of property rights, new institutional economics and Austrian economic theory.
UK researchers develop real‐time, optical diesel emission monitor
Authors: Bogue Robert W. , Aspey Robin
Published: October 2003

This article describes the development of a novel optical sensor, based on chromatic modulation, for characterising the particulate emissions from diesel engines, in situ and in real‐time.
Biometric developments provide scientific farming techniques
Authors: Connolly Christine
Published: October 2003

This paper concerns the use of image processing techniques and biometric sensors to measure the growth rate of animals without disrupting their natural behaviour.
Little and large at Sensor 2003 Nuremberg
Authors: Braggins Don
Published: October 2003

A sampling of new and intriguing sensing devices shown at the biennial Sensor exhibition on Nuremberg in May. Devices seen ranged from acoustic arrays several metres diameter to tiny motion sensors and Hall effect devices. Miniaturisation was a constant theme.
US company launches first MEMS‐based IR detector array
Authors: Bogue Robert W.
Published: October 2003

Describes the world's first uncooled infrared array sensor based on micro electro‐mechanical systems technology. Each pixel comprises a cantilever which bends as it warms up. The system measures the capacitance between each cantilever and a metal substrate.
Biosensors for monitoring the environment
Authors: Bogue Robert W.
Published: October 2003

This paper considers the role of biosensors for monitoring the environment. A selection of existing products and competitive techniques such as biochemical assays and laboratory analysis which presently dominate the business are discussed. A number of research activities and themes are considered. Conclusion are drawn on the prospects for environmental biosensors.
A process to control diaphragm thickness with a provision for back to front alignment in the fabrication of polysilicon piezoresistive pressure sensor
Authors: Akhtar J. , Dixit B.B. , Pant B.D. , Deshwal V.P. , Joshi B.C.
Published: October 2003

A MEMS process is described to control diaphragm thickness with an integrated provision for back to front alignment in the fabrication of a polysilicon piezoresistive pressure sensor. The end point detection for the diaphragm etching is suitably incorporated in the process so that it is also used for the back‐to‐front alignment. The proposed process is cost‐effective and suitable for the batch fabrication of the pressure sensor.
Feasibility of a new sensor for water activity determination
Authors: Ferblantier G. , Sorli B. , Pascal‐Delannoy F. , Boyer A.
Published: October 2003

In this paper, we propose a new way for the determination of aw in fresh and salt meat. The principle is founded on the analysis of a small air volume inside the product. First we describe the fundamental definition of water activity, the state‐of‐the‐art of commercial aw meters, the effects of aw on microbiology in food. In the second step, after a description of the sensor, the principle and the procedure of measurement are explained. The measurements of aw are realized in meat at different stages of drying. Reproducibility and the temperature effect are particularly analyzed.
Automatic recognition by gait: progress and prospects
Authors: Nixon Mark S. , Carter John N. , Grant Michael G. , Gordon Layla , Hayfron‐Acquah James B.
Published: October 2003

Recognising people by their gait is a biometric of increasing interest. Recently, analysis has progressed from evaluation by few techniques on small databases with encouraging results to large databases and still with encouraging results. The potential of gait as a biometric was encouraged by the considerable amount of evidence available, especially in biomechanics and literature. This potential motivated the development of new databases, new technique and more rigorous evaluation procedures. We adumbrate some of the new techniques we have developed and their evaluation to gain insight into the potential for gait as a biometric. In particular, we consider implications for the future. Our work, as with others, continues to provide encouraging results for gait as a biometric, let alone as a human identifier, with a special regard for recognition at a distance.
A review of digital data acquisition hardware and software for a portable electronic nose
Authors: Arshak K. , Lyons G.M. , Cunniffe C. , Harris J. , Clifford S.
Published: October 2003

This paper discusses the digital hardware and software that is required for data acquisition in a portable electronic nose (e‐nose) system. A review of current e‐nose systems is presented highlighting the methods employed by these systems to acquire the data from the sensor head.
Morphological capacitive sensors for air bag applications
Authors: Lucas Jérôme , Batis Christophe , Holé Stéphane , Ditchi Thierry , Launay Claude , Da Silva Joaquim , Dirand Hervé , Chabert Laurent , Pajon Marc
Published: October 2003

The Federal Motor Vehicle Safety Standards No. 208 includes directives rendering the morphological estimation of passengers mandatory for advanced air bag systems. The dynamic automatic suppression system uses both the morphological and positional information about the passenger to allow or prevent air bag deployment. Various solutions have been proposed to obtain these information by using capacitive sensors. This paper presents a method, that makes possible use of such sensors in the car industry by correcting their responses from these perturbing parameters.
Experimental and numerical behaviour of railway rivets under quasi‐static promptings
Authors: Cebulski L. , Boneill C. , Drazetic P. , Markiewicz E.
Published: October 2003

The riveting with blind rivets is extensively used in railway structures, which are mainly composed of aluminium. The lack of knowledge in this process makes the railway constructors to over‐proportion the number of rivets used in the structures and to perform a lot of tests in order to validate them. To better understand the different phenomena occurring during this process, a numerical model has been made, based on experimental tests. Considering the diversity of assemblies found in a railway structure (various diameter values of rivet, thickness and multiple materials of sheet metal assemblies, etc.), we propose a methodology based on the simulation of their behaviour. The numerical model allows to avoid high characterisation costs based only on experience.
Initial solution estimation to speed up inverse approach in stamping modeling
Authors: Guo Y.Q. , Naceur H. , Debray K. , Bogard F.
Published: October 2003

Nowadays, simplified inverse or one step approaches for the sheet forming modeling are increasingly used in the automobile industry, since they allow to quickly realize the preliminary design and especially to optimize the process parameters. These methods often based on implicit static algorithms cause sometimes convergence problems because of strong non‐linearities. This paper deals with several initial guess methods to speed up the convergence of the implicit static solver used in the inverse approach for stamping modeling. The blank's mesh as initial solution is obtained by geometrical considerations based on the known shape of the final 3D workpiece. Three algorithms for the estimation of the blank's mesh have been developed and compared. The application to several industrial problems shows their efficiency and performance.
On the performance of enhanced strain finite elements in large strain deformations of elastic shells
Authors: Sansour Carlo , Feih Stefanie , Wagner Werner
Published: October 2003

This paper is concerned with the performance of shell finite elements, well established in locking‐free computations with linear constitutive laws, in the case of non‐linear elastic material behaviour. Specifically enhanced strain elements are focused on. It is shown that the element behaviour depends on the resulting form of the stress tensor. Phenomenological models for highly non‐linear and elastically deforming rubber, like that of Odgen, are compared with the statistical‐based constitutive model developed by Arruda and Boyce. Whereas computations with the Odgen or any equivalent phenomenological model prove unstable, the behaviour of the enhanced elements, when the statistical model is applied, is shown to be superior. The behaviour is attributed to the mathematical form of the resulting stress tensor.
Voluntary social reporting in three FTSE sectors: a comment on perception and legitimacy
Authors: Campbell David , Craven Barrie , Shrives Philip
Published: October 2003

In examining the effects of the Exxon Valdez oil spillage on corporate social reporting (CSR) in the annual reports of oil companies, Patten suggested examining companies in other industries and their response to social (e.g. environmental) threats. This paper examines environmental and social reporting in five companies representing three FTSE sectors, selected according to an intuitive understanding of society’s perceptions of their depth of “sin” or supposed unethical behaviour. Social disclosure data were captured from annual corporate reports between 1975 and 1997. Results suggest that legitimacy theory may be an explanation of disclosure in some cases but not in others. The distorting effects of perception (of legitimacy‐threatening factors) and the increase in choices of disclosure media partly explain the mixed results and these factors and it is suggested, challenge the usefulness of future “annual‐report only” studies.
Risk management: The reinvention of internal control and the changing role of internal audit
Authors: Spira Laura F. , Page Michael
Published: October 2003

The publication of the Turnbull guidance represented a radical redefinition of the nature of internal control as a feature of corporate governance in the UK, explicitly aligning internal control with risk management. This paper explores this change, using sociological perspectives on risk and its conceptualisation to frame the debate about internal control and risk management within the UK corporate governance arena – the most recent manifestation of an ongoing competition for the control of economic and social resources. The paper demonstrates that developments in corporate governance reporting requirements offer opportunities for the appropriation of risk and its management by groups wishing to advance their own interests. This is illustrated by a review of recent changes in internal audit.