bluuebunny/crossref_metadata_2025 huggingface dataset:
A framework for e‐learning as a tool for knowledge management
Authors: Wild Rosemary H. , Griggs Kenneth A. , Downing Tanya
Published: September 2002

A common thread among the plethora of definitions of knowledge management is that its objective is to identify and leverage the collective knowledge in an organization to help organizations compete and survive. One potential lever is e‐learning, the creation and distribution of organizational knowledge through the online delivery of information, communication, education, and training. John Chambers, of Cisco Systems, said: “The two great equalizers in life are the Internet and education”, so why not fuse the two to provide an efficient way to empower a workforce with the skills and knowledge it needs to compete amid the rapid pace of change in business? In this paper we discuss the relationship between knowledge management and e‐learning and present a framework for employing e‐learning as a valuable tool for knowledge management. The framework encompasses the planning and implementation elements necessary for organizations to leverage existing technologies and implement new ones to promote organizational learning and contribute to the management of organizational knowledge.
IT project uncertainty, planning and success
Authors: Aladwani Adel M.
Published: September 2002

In this paper, I examine the mediating effect of project planning on the link between three project uncertainty variables (project size, project diversity, and technical complexity) and IT project success in a developing country. The proposed model is validated using a field survey of 42 IT project leaders from Kuwait. The overall findings give support to the proposed model and to the role of project planning as a mediator between project uncertainty and project success. However, the results challenge the traditional conception by past IT implementation research regarding the direct negative role of uncertainty in IT projects. This finding may be understood in light of the different manifestations that uncertainty may have for IT projects in developing countries. Implications of the findings and directions for future research are discussed.
Political and moralising moments: on visions of IT in Danish health care
Authors: Bruun Jensen Casper , Ross Winthereik Brit
Published: September 2002

In this paper, we discuss the production of visions for IT in Danish health care. Visions are not propagated “from above” but are produced through translation processes, in which contents change as they are inscribed in ministerial reports, leaflets or recommendations. This is illustrated by two cases: the electronic patient record at Hvidovre Hospital (HVEPS) and the Digital Doctor Project (DDP). Following STS‐studies we propose to analyse such reports as material agents with distinctive capacities and features. Prominent among those is the ability of such reports to carry “contradictory” messages. We analyse this capacity as a strength as it enables reports to bind together various people in various contexts, rather than as a weakness. We propose the concept of political moment as a tool that can capture the material heterogeneity and the unexpectedness of translations. The concept of moralising moment is introduced to identify accounts in which such processes are glossed or covered.
Interaction, transformation and information systems development – an extended application of Soft Systems Methodology
Authors: Rose Jeremy
Published: September 2002

Soft Systems Methodology (SSM) has long been involved in information systems development through the medium of action research. Its social constructivist paradigm and managerial focus distinguish it from most software engineering development approaches. Checkland’s underlying view of systems development, however, is heavily influenced by traditional waterfall models – something of a contradiction. This paper uses recent developments in SSM to develop a more appropriate systems development concept: the interaction‐transformation‐interaction (ITI) model. The model views systems development primarily as a social and managerial task, rather than a technical one. It was successfully used (in conjunction with developed forms of SSM which incorporate analysis based on structuration theory) to structure the development of an intranet in a university department. The experience led to a further series of reflections on the model.
Lifelong learning and SMEs: issues for research and policy
Authors: Johnson Steve
Published: September 2002

Research evidence suggests that SMEs are significantly less likely than larger employers to provide or fund formal training leading to qualifications for employees. The training (or more accurately learning) that does take place in most SMEs tends to be informal, on‐the‐job and related to short‐term business objectives or problems. There are strong arguments to suggest that this type of approach is perfectly rational from the point of view of the small business, but may not produce the optimum level or mix of skills for the economy as a whole. Moreover, there is little convincing evidence to suggest that increased investment in formal training leads automatically to improved business performance for SMEs. Research findings raise a number of issues for policy makers and others who are trying to promote the concept of lifelong learning, and associated policy initiatives, to those who own, manage and/or work in SMEs. This paper suggests a number of directions that should be taken by researchers’ policy makers, to promote lifelong learning among SMEs.
Small firm responses to employment regulation
Authors: Harris Lynette
Published: September 2002

Examines the impact of employment regulation on owner‐manager approaches to the employment relationship at the level of the individual firm. While there was no reported principled opposition to extending employment rights as suggested by a number of earlier studies, the cumulative effect of recent legislation was perceived by owner‐managers to be reducing their competitiveness by placing costly and time‐consuming demands on the smaller business. The case study companies were increasingly formalising their employment processes largely to defend their decisions against potential litigation. Despite certain acknowledged benefits, this increasing proceduralisation was held to be detrimental to the informality and flexibility viewed as essential to effective working relationships in the smaller enterprise. Continuing recruitment difficulties combined with the costs associated with expanding regulation led the majority of the case study companies to identify an investment in automation and labour‐saving equipment as a preferable long‐term option to the expansion of the workforce.
Drug resistance in HIV‐1 protease: Flexibility‐assisted mechanism of compensatory mutations
Authors: Piana Stefano , Carloni Paolo , Rothlisberger Ursula
Published: September 2002

The emergence of drug‐resistant variants is a serious side effect associated with acquired immune deficiency syndrome therapies based on inhibition of human immunodeficiency virus type 1 protease (HIV‐1 PR). In these variants, compensatory mutations, usually located far from the active site, are able to affect the enzymatic activity via molecular mechanisms that have been related to differences in the conformational flexibility, although the detailed mechanistic aspects have not been clarified so far. Here, we perform multinanosecond molecular dynamics simulations on L63P HIV‐1 PR, corresponding to the wild type, and one of its most frequently occurring compensatory mutations, M46I, complexed with the substrate and an enzymatic intermediate. The quality of the calculations is established by comparison with the available nuclear magnetic resonance data. Our calculations indicate that the dynamical fluctuations of the mutated enzyme differ from those in the wild type. These differences in the dynamic properties of the adducts with the substrate and with the gem‐diol intermediate might be directly related to variations in the enzymatic activity and therefore offer an explanation of the observed changes in catalytic rate between wild type and mutated enzyme. We anticipate that this “flexibility‐assisted” mechanism might be effective in the vast majority of compensatory mutations, which do not change the electrostatic properties of the enzyme.
The SPOT technique as a tool for studying protein tyrosine phosphatase substrate specificities
Authors: Espanel Xavier , Huguenin‐Reggiani Martine , van Huijsduijnen Rob Hooft
Published: September 2002

The activity of protein tyrosine phosphatases (PTPs) is restricted by their substrate specificities. The analysis of PTP specificity was greatly helped by the discovery that “substrate‐trapping” PTP mutants, such as PTP‐1B D181A, stably and specifically bind their substrates. We have set up a PTP substrate specificity assay based on the SPOT technique, which involves the microsynthesis of (phospho)peptides on membranes. To validate this approach, substrate trapping PTP‐1B was tested on its cognate ligand, the autophosphorylated insulin receptor (IR). On SPOT membranes, IR peptides with phosphotyrosine 1163 were efficiently bound by PTP1B D181A, and dephosphorylated by PTP‐1B. Phosphotyrosine 1163 was preferred over the neighboring 1158 and 1162 phosphotyrosines. PTP‐1B also recognized IR‐like motifs in Trk autophosphorylation domains, and STAT 5 phosphopeptides. Using a gridded 20‐by‐20 SPOT library, we show that peptides with the YZM motif (Z: phosphotyrosine) are the strongest ligands for PTP‐1B D181A, but not the optimal substrates for dephosphorylation by wild‐type PTP1B. In addition we show that PTP‐1B and PTP‐β dephosphorylation efficiency is strongly modulated by the introduction of phospho‐serine or phospho‐threonine in their cognate phospho‐tyrosine substrates. Altogether our data illustrate that the SPOT technique is a highly efficient tool for the study of PTP substrate specificity.
A kinetic study of β‐lactoglobulin amyloid fibril formation promoted by urea
Authors: Hamada Daizo , Dobson Christopher M.
Published: September 2002

The formation of fibrillar aggregates by β‐lactoglobulin in the presence of urea has been monitored by using thioflavin T fluorescence and transmission electron microscopy (TEM). Large quantities of aggregated protein were formed by incubating β‐lactoglobulin in 3–5 M urea at 37°C and pH 7.0 for 10–30 days. The TEM images of the aggregates in 3–5 M urea show the presence of fibrils with diameters of 8–10 nm, and increases in thioflavin T fluorescence are indicative of the formation of amyloid structures. The kinetics of spontaneous fibrillogenesis detected by thioflavin T fluorescence show sigmoidal behavior involving a clear lag phase. Moreover, addition of preformed fibrils into protein solutions containing urea shows that fibril formation can be accelerated by seeding processes that remove the lag phase. Both of these findings are indicative of nucleation‐dependent fibril formation. The urea concentration where fibril formation is most rapid, both for seeded and unseeded solutions, is ∼5.0 M, close to the concentration of urea corresponding to the midpoint of unfolding (5.3 M). This result indicates that efficient fibril formation involves a balance between the requirement of a significant population of unfolded or partially unfolded molecules and the need to avoid conditions that strongly destabilize intermolecular interactions.
Cannabinoid receptor‐G protein interactions: Gαi1‐bound structures of IC3 and a mutant with altered G protein specificity
Authors: Ulfers Amy L. , McMurry Jonathan L. , Miller Alexander , Wang Ligong , Kendall Debra A. , Mierke Dale F.
Published: September 2002

The structure of the C‐terminal region of the third cytoplasmic loop (IC3) of the cannabinoid receptor one (CB1) bound to Gαi1 has been determined using transferred nuclear Overhauser effects (NOEs). The wild‐type IC3 sequence is helical when associated with Gαi1. In contrast, a peptide containing the amino‐acid inversion, Ala341‐Leu342 adopts a single turn. These findings correlate with the attenuated Gi association of CB1 with the Ala341‐Leu342 mutation previously observed in vivo and the diminished stimulation of Gαi1 GTPase activity by the corresponding peptide demonstrated in vitro here. These results, the first to report the structure of a GPCR domain while associated with G protein, imply the C‐terminus of CB1 IC3, a region with high‐sequence conservation among G‐protein coupled receptors, must be helical for efficient coupling and activation of the Gi protein.
Gamma Interferon-Dependent Protection of the Mouse Upper Respiratory Tract following Parenteral Immunization with a Respiratory Syncytial Virus G Protein Fragment
Authors: Plotnicky-Gilquin Helene , Cyblat-Chanal Dominique , Aubry Jean-Pierre , Champion Thierry , Beck Alain , Nguyen Thien , Bonnefoy Jean-Yves , Corvaïa Nathalie
Published: September 2002

The protective mechanisms induced in the mouse upper respiratory tract (URT) after intraperitoneal immunization with G2Na, a recombinant respiratory syncytial virus (RSV) G protein fragment (amino acid residues 130 to 230), were investigated. This protection was recently shown to be mediated by CD4+T cells and to be critically dependent on the cysteines and amino acids 193 and 194 (H. Plotnicky-Gilquin, A. Robert, L. Chevalet, J.-F. Haeuw, A. Beck, J.-Y. Bonnefoy, C. Brandt, C.-A. Siegrist, T. N. Nguyen, and U. F. Power, J. Virol. 74:3455-3463, 2000). On G2Na, we identified a domain (amino acid residues 182 to 198) responsible for the T-helper-cell activity. This region coincided with a peptide designed AICK (residues 184 to 198) which includes the previously identified murine and human T-helper-cell epitope on the native G protein (P. W. Tebbey, M. Hagen, and G. E. Hancock, J. Exp. Med. 188:1967-1972, 1998). Immunization with AICK, in alum or complete Freund's adjuvant, significantly reduced nasal RSV titers in normal BALB/c mice. However, although lung protection was induced, in contrast to the case with live RSV, neither AICK nor G2Na was able to prevent nasal infection in gamma interferon (IFN-γ)-knockout mice. Anti-IFN-γ neutralizing antibodies partially inhibited URT protection after administration to G2Na-immunized BALB/c mice. Furthermore, while purified CD4+T cells from BALB/c mice immunized with G2Na or AICK significantly reduced lung and nasal infection of naive recipient mice after adoptive transfer, the cells from IFN-γ-knockout mice had no effect. Together, these results demonstrated for the first time that the T-helper-cell epitope of RSV G protein induces URT protection in mice after parenteral immunization through a Th1-type, IFN-γ-dependent mechanism.
Exchange of the C-Terminal Part of VP3 from Very Virulent Infectious Bursal Disease Virus Results in an Attenuated Virus with a Unique Antigenic Structure
Authors: Boot Hein J. , ter Huurne A. Agnes H. M. , Hoekman Arjan J. W. , Pol Jan M. , Gielkens Arno L. J. , Peeters Ben P. H.
Published: September 2002

Infectious bursal disease virus (IBDV) is the major viral pathogen in the poultry industry. Live attenuated serotype 1 vaccine strains are commonly used to protect susceptible chickens during their first 6 weeks of life. Wild-type serotype 1 IBDV strains are highly pathogenic only in chickens, whereas serotype 2 strains are apathogenic in chickens and other birds. Here we describe the replacement of the genomic double-stranded RNA (dsRNA) encoding the N- or C-terminal part of VP3 of serotype 1 very virulent IBDV (vvIBDV) (isolate D6948) with the corresponding part of serotype 2 (isolate TY89) genomic dsRNA. The modified virus containing the C-terminal part of serotype 2 VP3 significantly reduced the virulence in specific-pathogen-free chickens, without affecting the distinct bursa tropism of serotype 1 IBDV strains. Furthermore, by using serotype-specific antibodies we were able to distinguish bursas infected with wild-type vvIBDV from bursas infected with the modified vvIBDV. We are currently evaluating the potential of this recombinant strain as an attenuated live vaccine that induces a unique serological response (i.e., an IBDV marker vaccine).
Life Cycle Heterogeneity in Animal Models of Human Papillomavirus-Associated Disease
Authors: Peh Woei Ling , Middleton Kate , Christensen Neil , Nicholls Philip , Egawa Kiyofumi , Sotlar Karl , Brandsma Janet , Percival Alan , Lewis Jon , Liu Wen Jun , Doorbar John
Published: September 2002

Animal papillomaviruses are widely used as models to study papillomavirus infection in humans despite differences in genome organization and tissue tropism. Here, we have investigated the extent to which animal models of papillomavirus infection resemble human disease by comparing the life cycles of 10 different papillomavirus types. Three phases in the life cycles of all viruses were apparent using antibodies that distinguish between early events, the onset of viral genome amplification, and the expression of capsid proteins. The initiation of these phases follows a highly ordered pattern that appears important for the production of virus particles. The viruses examined included canine oral papillomavirus, rabbit oral papillomavirus (ROPV), cottontail rabbit papillomavirus (CRPV), bovine papillomavirus type 1, and human papillomavirus types 1, 2, 11, and 16. Each papillomavirus type showed a distinctive gene expression pattern that could be explained in part by differences in tissue tropism, transmission route, and persistence. As the timing of life cycle events affects the accessibility of viral antigens to the immune system, the ideal model system should resemble human mucosal infection if vaccine design is to be effective. Of the model systems examined here, only ROPV had a tissue tropism and a life cycle organization that resembled those of the human mucosal types. ROPV appears most appropriate for studies of the life cycles of mucosal papillomavirus types and for the development of prophylactic vaccines. The persistence of abortive infections caused by CRPV offers advantages for the development of therapeutic vaccines.
Epstein-Barr Virus-Induced Changes in B-Lymphocyte Gene Expression
Authors: Carter Kara L. , Cahir-McFarland Ellen , Kieff Elliott
Published: September 2002

To elucidate the mechanisms by which Epstein-Barr virus (EBV) latency III gene expression transforms primary B lymphocytes to lymphoblastoid cell lines (LCLs), the associated alterations in cell gene expression were assessed by using 4,146 cellular cDNAs arrayed on nitrocellulose filters and real-time reverse transcription-PCR (RT-PCR). A total of 1,405 of the 4,146 cDNAs were detected using cDNA probes from poly(A)+RNA of IB4 LCLs, a non-EBV-infected Burkitt's lymphoma (BL) cell line, BL41, or EBV latency III-converted BL41 cells (BL41EBV). Thirty-eight RNAs were consistently twofold more abundant in the IB4 LCL and BL41EBV than in BL41 by microarray analysis. Ten of these are known to be EBV induced. A total of 23 of 28 newly identified EBV-induced genes were confirmed by real-time RT-PCR. In addition, nine newly identified genes and CD10 were EBV repressed. These EBV-regulated genes encode proteins involved in signal transduction, transcription, protein biosynthesis and degradation, and cell motility, shape, or adhesion. Seven of seven newly identified EBV-induced RNAs were more abundant in newly established LCLs than in resting B lymphocytes. Surveys of eight promoters of newly identified genes implicate NF-κB or PU.1 as potentially important mediators of EBV-induced effects through LMP1 or EBNA2, respectively. Thus, examination of the transcriptional effects of EBV infection can elucidate the molecular mechanisms by which EBV latency III alters B lymphocytes.
Mitochondrial Targeting and Membrane Anchoring of a Viral Replicase in Plant and Yeast Cells
Authors: Weber-Lotfi Frédérique , Dietrich André , Russo Marcello , Rubino Luisa
Published: September 2002

Replication of the
Carnation Italian ringspot virus
genomic RNA in plant cells occurs in multivesicular bodies which develop from the mitochondrial outer membrane during infection. ORF1 in the viral genome encodes a 36-kDa protein, while ORF2 codes for the 95-kDa replicase by readthrough of the ORF1 stop codon. We have shown previously that the N-terminal part of ORF1 contains the information leading to vesiculation of mitochondria and that the 36-kDa protein localizes to mitochondria. Using infection, in vivo expression of green fluorescent protein fusions in plant and yeast cells, and in vitro mitochondrial integration assays, we demonstrate here that both the 36-kDa protein and the complete replicase are targeted to mitochondria and anchor to the outer membrane with the N terminus and C terminus on the cytosolic side. Analysis of deletion mutants indicated that the anchor sequence is likely to correspond approximately to amino acids 84 to 196, containing two transmembrane domains. No evidence for a matrix-targeting presequence was found, and the data suggest that membrane insertion of the viral proteins is mediated by an import receptor-independent signal-anchor mechanism relying on the two transmembrane segments and multiple recognition signals present in the N-terminal part of ORF1.
Phosphorylation of the Porcine Reproductive and Respiratory Syndrome Virus Nucleocapsid Protein
Authors: Wootton Sarah K. , Rowland Raymond R. R. , Yoo Dongwan
Published: September 2002

Porcine reproductive and respiratory syndrome virus (PRRSV) is a cytoplasmic RNA virus with the unique or unusual feature of having a nucleocapsid (N) protein that is specifically transported to the nucleolus of virus-infected cells. In this communication, we show that the N protein is a phosphoprotein. Phosphoamino acid analysis of authentic and recombinant N proteins demonstrated that serine residues were exclusively phosphorylated. The pattern of phosphorylated N protein cellular distribution in comparison with that of [
35
S]methionine-labeled N protein suggested that phosphorylation does not influence subcellular localization of the protein. Time course studies showed that phosphorylation occurred during, or shortly after, synthesis of the N protein and that the protein remained stably phosphorylated throughout the life cycle of the virus to the extent that phosphorylated N protein was found in the mature virion. Two-dimensional electrophoresis and acid-urea gel electrophoresis showed that one species of the N protein is predominant in virus-infected cells, suggesting that multiple phosphorylated isoforms of N do not exist.
INVARIANTS OF ELLIPTIC AND HYPERBOLIC CR-STRUCTURES OF CODIMENSION 2
Authors: EZHOV V. V. , ISAEV A. V. , SCHMALZ G.
Published: September 2002

We reduce CR-structures on smooth elliptic and hyperbolic manifolds of CR-codimension 2 to parallelisms thus solving the problem of global equivalence for such manifolds. The parallelism that we construct is defined on a sequence of two principal bundles over the manifold, takes values in the Lie algebra of infinitesimal automorphisms of the quadric corresponding to the Levi form of the manifold, and behaves "almost" like a Cartan connection. The construction is explicit and allows us to study the properties of the parallelism as well as those of its curvature form. It also leads to a natural class of "semi-flat" manifolds for which the two bundles reduce to a single one and the parallelism turns into a true Cartan connection.

In addition, for real-analytic manifolds we describe certain local normal forms that do not require passing to bundles, but in many ways agree with the structure of the parallelism.
NUMERICAL BOUNDS FOR DEGENERATIONS OF SURFACES OF GENERAL TYPE
Authors: LEE YONGNAM
Published: September 2002

This paper considers bounds on the numerical properties of degenerations of surfaces of general type. Under suitable assumptions, we give explicit bounds for the number of singularities outside the double curve and for the number of components in a relative canonical model. We also give bounds for the index of singularities in a special case, which illustrates clearly the reason behind the bounds for the index in a relatively minimal permissible degeneration.
EQUIVARIANT POISSON COHOMOLOGY AND A SPECTRAL SEQUENCE ASSOCIATED WITH A MOMENT MAP
Authors: GINZBURG VIKTOR L.
Published: September 2002

We introduce and study a new spectral sequence associated with a Poisson group action on a Poisson manifold and an equivariant momentum mapping. This spectral sequence is a Poisson analog of the Leray spectral sequence of a fibration. The spectral sequence converges to the Poisson cohomology of the manifold and has the E2-term equal to the tensor product of the cohomology of the Lie algebra and the equivariant Poisson cohomology of the manifold. The latter is defined as the equivariant cohomology of the multi-vector fields made into a G-differential complex by means of the momentum mapping. An extensive introduction to equivariant cohomology of G-differential complexes is given including some new results and a number of examples and applications are considered.
BULK AMORPHOUS Zr57Cu20Al10Ni8Ti5 AND Zr55Cu19Al8Ni8Ti5Si5 ALLOYS PREPARED BY ARC MELTING
Authors: BASKOUTAS S. , KAPAKLIS V. , POLITIS C.
Published: September 2002

We have produced bulk amorphous materials by quenching arc melted melts in water cooled copper die. Alloys of the composition Zr 57 Cu 20 Al 10 Ni 8 Ti 5 and Zr 55 Cu 19 Al 8 Ni 8 Ti 5 Si 5 were produced in the form of small cylinders with a diameter of 3 mm and a length of 25 mm. The alloys were investigated by X-ray diffraction and thermal analysis to determine the structure and thermal properties. Complete amorphous X-ray patterns were observed for both alloys. The glass transition temperature is 362°C for the Zr 57 Cu 20 Al 10 Ni 8 Ti 5 alloy and 363°C for the Zr 55 Cu 19 Al 8 Ni 8 Ti 5 Si 5 alloy. The crystallization temperature of the Zr 57 Cu 20 Al 10 Ni 8 Ti 5 alloy was measured to be 414.6°C. The Zr 55 Cu 19 Al 8 Ni 8 Ti 5 Si 5 alloy has a higher crystallization temperature of 425.5°C.
Transgenic overexpression of human IL-17E results in eosinophilia, B-lymphocyte hyperplasia, and altered antibody production
Authors: Kim Mee Rhan , Manoukian Raffi , Yeh Richard , Silbiger Scott M. , Danilenko Dimitry M. , Scully Sheila , Sun Jilin , DeRose Margaret L. , Stolina Marina , Chang David , Van Gwyneth Y. , Clarkin Kristie , Nguyen Hung Q. , Yu Yan Bin , Jing Shuqian , Senaldi Giorgio , Elliott Gary , Medlock Eugene S.
Published: September 2002

We have identified and cloned a novel human cytokine with homology to cytokines of the interleukin-17 (IL-17) family, which we have termed human IL-17E (hIL-17E). With the identification of several IL-17 family members, it is critical to understand the in vivo function of these molecules. We have generated transgenic mice overexpressing hIL-17E using an apolipoprotein E (ApoE) hepatic promoter. These mice displayed changes in the peripheral blood, particularly, a 3-fold increase in total leukocytes consisting of increases in eosinophils, lymphocytes, and neutrophils. Splenomegaly and lymphoadenopathy were predominant and included marked eosinophil infiltrates and lymphoid hyperplasia. CCR3+ eosinophils increased in the blood and lymph nodes of the transgenic mice by 50- and 300-fold, respectively. Eosinophils also increased 8- to 18-fold in the bone marrow and spleen, respectively. In the bone marrow, most of the eosinophils had an immature appearance. CD19+ B cells increased 2- to 5-fold in the peripheral blood, 2-fold in the spleen, and 10-fold in the lymph nodes of transgenic mice, whereas CD4+ T lymphocytes increased 2-fold in both blood and spleen. High serum levels of the cytokines IL-2, IL-4, IL-5, granulocyte colony-stimulating factor, eotaxin, and interferon γ were observed. Consistent with B-lymphocyte increases, serum immunoglobulin (Ig) M, IgG, and IgE were significantly elevated. Antigenic challenge of the transgenic mice with keyhole limpet hemocyanin (KLH) resulted in a decrease in anti-KLH IgG accompanied by increases of anti-KLH IgA and IgE. In situ hybridization of transgenic tissues revealed that IL-17Rh1 (IL-17BR/Evi27), a receptor that binds IL-17E, is up-regulated. Taken together, these data indicate that IL-17E regulates hematopoietic and immune functions, stimulating the development of eosinophils and B lymphocytes. The fact that hIL-17E overexpression results in high levels of circulating eosinophils, IL-4, IL-5, eotaxin, and IgE suggests that IL-17E may be a proinflammatory cytokine favoring Th2-type immune responses.
CCR5-binding chemokines modulate CXCL12 (SDF-1)–induced responses of progenitor B cells in human bone marrow through heterologous desensitization of the CXCR4 chemokine receptor
Authors: Honczarenko Marek , Le Yi , Glodek Aleksandra M. , Majka Marcin , Campbell James J. , Ratajczak Mariusz Z. , Silberstein Leslie E.
Published: September 2002

Although the SDF-1 (CXCL12)/CXCR4 axis is important for B-cell development, it is not yet clear to what extent CC chemokines might influence B lymphopoiesis. In the current study, we characterized CC chemokine receptor 5 (CCR5) expression and function of primary progenitor B-cell populations in human bone marrow. CCR5 was expressed on all bone marrow B cells at levels between 150 and 200 molecules per cell. Stimulation of bone marrow B cells with the CCR5-binding chemokine macrophage inflammatory protein 1β (MIP-1β; CCL4) did not cause chemotaxis, but CCL4 was able to trigger potent calcium mobilization responses and activation of the mitogen-activated protein kinase (MAPK) pathway in developing B cells. We also determined that CCR5-binding chemokines MIP-1α (CCL3), CCL4, and RANTES (CCL5), specifically by signaling through CCR5, could affect all progenitor B-cell populations through a novel mechanism involving heterologous desensitization of CXCR4. This cross-desensitization of CXCR4 was manifested by the inhibition of CXCL12-induced calcium mobilization, MAPK activation, and chemotaxis. These findings indicate that CCR5 can indeed mediate biologic responses of bone marrow B cells, even though these cell populations express low levels of CCR5 on their cell surface. Thus, by modulation of CXCR4 function, signaling through CCR5 may influence B lymphopoiesis by affecting the migration and maturation of B-cell progenitors in the bone marrow microenvironment.
Interleukin 7 worsens graft-versus-host disease
Authors: Sinha Manoj L. , Fry Terry J. , Fowler Daniel H. , Miller Georgina , Mackall Crystal L.
Published: September 2002

Impaired immune reconstitution has moved to the forefront of clinical problems limiting progress in allogeneic bone marrow transplantation (BMT). The identification of therapies that can enhance immune reconstitution by increasing thymopoiesis is critical to solving this problem. Interleukin 7 (IL-7) is the most potent thymopoietic cytokine identified thus far. To study the effects of IL-7 on immune reconstitution and graft-versus-host disease (GVHD) following allogeneic BMT, we administered recombinant human IL-7 (rhIL-7) in a murine parent into an F1 model. Results showed that rhIL-7 therapy lowered the “threshold” T-cell dose required to induce both clinical signs of GVHD as well as lethal GVHD. Histologic analysis of GVHD target tissues revealed that rhIL-7 increased the degree of inflammation and tissue damage observed at all T-cell doses studied, but did not change the pattern of organs affected or the histologic appearance of the GVHD within target organs. In addition, we evaluated the capacity for rhIL-7 to enhance thymopoiesis in the setting of allogeneic T cell–depleted (TCD) and T-cell–replete BMT. We observed that rhIL-7 therapy enhanced thymic function in TCD allogeneic BM transplant recipients, but not in animals that received even modest doses of T cells presumably due to thymic toxicity of the graft-versus-host reaction. Thus, caution must be exercised as IL-7 is developed clinically as an immunorestorative agent for use in the setting of allogeneic BMT. These results suggest that use of IL-7 should be limited to the setting of TCD BMT to obtain the greatest benefit on immune competence with the least toxicity.
The World Health Organization (WHO) classification of the myeloid neoplasms
Authors: Vardiman James W. , Harris Nancy Lee , Brunning Richard D.
Published: September 2002

A World Health Organization (WHO) classification of hematopoietic and lymphoid neoplasms has recently been published. This classification was developed through the collaborative efforts of the Society for Hematopathology, the European Association of Hematopathologists, and more than 100 clinical hematologists and scientists who are internationally recognized for their expertise in hematopoietic neoplasms. For the lymphoid neoplasms, this classification provides a refinement of the entities described in the Revised European-American Lymphoma (REAL) Classification—a system that is now used worldwide. To date, however, there has been no published explanation or rationale given for the WHO classification of the myeloid neoplasms. The purpose of this communication is to outline briefly the WHO classification of malignant myeloid diseases, to draw attention to major differences between it and antecedent classification schemes, and to provide the rationale for those differences.
Heparin acts synergistically with interleukin-11 to induce STAT3 activation and in vitro osteoclast formation
Authors: Walton Kimberly J. , Duncan Joanne M. , Deschamps Paula , Shaughnessy Stephen G.
Published: September 2002

We have previously demonstrated that long-term heparin treatment causes cancellous bone loss in rats due in part to an increase in the number of osteoclasts lining the trabecular bone surface. In the present study, we investigated this phenomenon by examining the ability of heparin to synergistically enhance interleukin-11 (IL-11)–induced osteoclast formation. Treatment of murine calvaria and bone marrow cells with IL-11 was found to induce the formation of tartrate-resistant acid phosphatase-positive (TRAP+) multinucleated cells (MNCs) in a dose-dependent fashion. No effect was seen when cocultures were treated with heparin alone. However, when cocultures were treated with both IL-11 and heparin, IL-11's ability to induce TRAP+ MNC formation was enhanced 6-fold. In an attempt to resolve the mechanism responsible for this effect, we examined the ability of heparin to influence IL-11 signaling using murine calvaria cells. Heparin was found to enhance both IL-11–induced STAT3-DNA complex formation and transactivation without altering either STAT3 (signal transducer and activator of transcription-3) tyrosine or serine phosphorylation. Heparin was also found to enhance IL-11's ability to induce the expression of both receptor activator of nuclear factor–κB ligand (RANKL) and glycoprotein (gp) 130. When taken together, these findings suggest a plausible mechanism by which heparin may cause increased osteoclastogenesis and therefore bone loss when administered long-term.
Minireview: Insights from Insulin-Like Growth Factor Binding Protein Transgenic Mice
Authors: Silha Josef V. , Murphy Liam J.
Published: September 2002

The existence of abundant high affinity binding proteins for the IGFs, the IGF binding proteins (IGFBPs), was first demonstrated more than 40 yr ago in the very early days of somatomedin research. With the development of molecular techniques and transgenic and knockout mouse models, the nature, complexity, and redundancy of the IGFBPs have now started to be elucidated. Indeed the functional role of the circulating IGFs and the originally proposed endocrine somatomedin hypothesis have recently been questioned. The limited reports to date indicate that IGFBP knockout mice have few phenotypic manifestations. In contrast, overexpression of IGFBPs in transgenic mice is associated with manifestations that provide some insight into the physiological role of the binding proteins. The predominant effect of generalized or tissue-specific overexpression of the IGFBPs has been growth inhibition as would be anticipated from inhibition of the actions of IGF-I and -II. In addition, impaired glucose homeostasis and reduced fecundity have been observed in both IGFBP-1- and IGFBP-3-overexpressing transgenic mice. This review examines the data reported to date for transgenic mouse models that overexpress IGFBPs. In addition, data from transgenic mice that overexpress the acid-labile subunit, an important component of the ternary complex, have also been reviewed.
Lichen Succession on Wilkiea Macrophylla Leaves
Authors: Rogers R. W. , Barnes A. , Conran J. G.
Published: September 2002

Changes in foliicolous lichen populations of the shrub Wilkiea macrophylla in rainforest at Mt Glorious (south-east Queensland) were observed in the field for 3 years. Leaves successively distal from the twig apices were treated as a chronosequence for lichen successional studies. Five species of lichen each colonized more than 50° 0 of the leaves, and leaves successively distal from the apex showed increasing mean species number. Lichen cover rose until the seventh most distal leaf from the first colonized leaf along a twig, reaching 52%. More distal (older) leaves had apparently lower cover. Different lichen species show different instantaneous colonization rates that vary with time. The sequence of lichen colonization and subsequent community composition is best described by a ‘Tolerance’ model of succession if a single leaf is selected as the unit or with a ‘Chronic Disturbance’ model if a leaf population is considered.
The Genus Sarcogyne (Acarosporaceae) in Antarctica
Authors: Seppelt R. D. , Nimis P. L. , Castello M.
Published: September 2002

Sarcogyne angulosa C. W. Dodge & G. E. Baker, described as an endemic from continental Antarctic localities, is reduced to synonymy with S. privigna (Ach.) A. Massal., a species known from Europe, North America, North Africa and Saudi Arabia, and now Antarctica. The relationship to Polysporina simplex (Davies) Vězda is discussed. It is suggested that the name Sarcogyne grisea Dodge, also described as an Antarctic endemic, should be abandoned. Sarcogyne medusula Dodge is transferred to Lecidea [Lecidea medusula (C. W. Dodge) Hertel comb, nov.], a Maritime- and Subantarctic species.
A Molecular Approach to the Circumscription and Evaluation of Some Genera Segregated from Parmelia S. Lat
Authors: Crespo Ana , Cubero Oscar F.
Published: September 2002

New sequences have been produced of the ITS rDNA region of twenty-nine species of Parmeliaceae and analysed by neighbour-joining maximum likelihood distance analysis, and maximum parsimony analysis. Twelve monophyletic groups have been identified, most of which correspond to proposed generic segregated from Parmelia s. lat. Parmelia and Parmelina, Melanelia, and Punctelia appear as independent monophyletic groups; the type species of the two latter genera were, however, not included in the analysis. The parsimony analysis does not support Xanthoparmelia as a monophyletic group separate from Neofuscelia, and Rimelia reticulate is nested within Parmotrema. Parmelinopsis horrescens is more closely related to Hypotrachyna revolute than to Parmelina. Genetic distance values suggest that Flavoparmelia caperata is closer to Parmotrema than to other taxa included, and that Platismatia glauca and Hypogymnia tubulosa are closer to Parmelia s. lat. than to the Physciaceae. However, there is no conclusive support for any of thelatter groupings in the parsimony analysis. We conclude that the ITS region contains valuable information for studying generic delimitations within the family Parmeliaceae, but our study suggests that this region will not conclusively resolve within-family relationships in this group.
Molecular Phylogeny of the Lichen Families Cladoniaceae, Sphaerophoraceae, and Stereocaulaceae (Lecanorales, Ascomycotina)
Authors: Wedin Mats , DÖring Heidi , Ekman Stefan
Published: September 2002

Maximum parsimony analysis of nuclear SSU rDNA sequences was utilized to infer the phylogenetic relationships of representatives of the macrolichen families Cladoniaceae, Sphaerophoraceae, and Stereocaulaceae (Lecanorales subord. Cladoniineae, Ascomycotina). Farris’ parsimony jackknifing, and a similar jackknife strategy with branch-swapping and multiple addition sequences in PAUP*, were performed to assess branch support. The results indicate that the Sphaerophoraceae should be emended to include Neophyllis (formerly Cladoniaceae or Stereocaulaceae) and Austropeltum (formerly Stereocaulaceae), and it is suggested that the type of boundary tissue present is a synapomorphy for the family. The families Sphaerophoraceae and Bacidiaceae form a clade, together with Psora decipiens, Tephromela atra and Scoliciosporum umbrinum. The Cladoniaceae should be emended to include Pilophorus, and the genera Metus, Cladia and Heterodea should also be included in the family. The sometimes-recognized families Cladiaceae and Heterodeaceae are shown to be derived from within Cladoniaceae. The Stereocaulaceae is recircumscribed to accommodate Stereocaulon only. Neither the possession of podetia/ pseudopodetia, a dimorphic, cladoniiform thallus, nor the presence of cephalodia, is a morphological synapomorphy for a monophyletic group in our analysis. Optimising ascus structures onto one of the most parsimonious trees suggest that tube-like apical structures may well be primitive characteristics within the Lecanorales. The two lecanoralean suborders Lecanorineae and Cladonineae are both paraphyletic groups in the present analysis. It is pointed out that if further studies confirm that Stereocaulon is the sister-group to the Cladoniaceae, as circumscribed here, then there may be no reason to accept the two families Cladoniaceae and Stereocaulaceae as distinct. Branch-swapping and several random-addition sequencesimprove resolution, adding several supported groups in the topology, and improve support values for groups already supported by parsimony jackkniring analyses, and we suggest a procedure for implementing this by using PAUP*
Effects of Wave Exposure and Aspect on Hong Kong Supralittoral Lichens
Authors: Chu F. Joanna , Seaward Mark R. D. , John Hodgkiss I.
Published: September 2002

The effects of wave exposure and aspect on the zonation of supralittoral lichens were studied at 14 sites in Hong Kong. In general, increasing wave exposure raised the supralittoral zones and extended their vertical widths. A higher lichen cover in the lower zones (Zones 1 and 2)l was found with greater wave exposures, but the opposite was true for upper zones (Zones 3 and 4). Lichen diversity was greater with increased wave exposure in three out of the four zones (Zones 2–4). The effects of aspect are mainly due to the prevailing winds, which resulted in south- and east-facing shores supporting a higher cover and diversity of lichens. The distribution patterns of lichens on this subtropical seashore differed from previous studies in the temperate regions of the northern hemisphere.
A Synopsis of the Genera Skyttea, Llimoniella and Rhymbocarpus (Lichenicolous Ascomycota, Leotiales)
Authors: Diederich Paul , Etayo Javier
Published: September 2002

The genus Skyttea is characterized by urceolate ascomata, with a narrow pore when young, a greenish or brownish, rarely reddish exciple of conglutinate hyphae with subglobose to ± cylindrical lumina, bordered near the margin by hyaline to greenish or brownish, usually smooth, straight hairs, the absence of periphyses, rarely branched and apically hardly thickened paraphyses, asci and a hymenium that are entirely I — and KI —, a thin lateral and a very thick apical ascus wall with a small ocular chamber, and normally aseptate ascospores. It is considered to belong to the Leotiales and not to the Ostropales. It comprises at least 17 species, including S. caesii sp. nov., S. carboneae sp. nov., S. lecanorae sp. nov., S. mayrhoferi sp. nov., S. pyrenulae sp. nov., S. radiatilis comb, nov., S. tavaresae. sp. nov. and S. thelotrematis sp. nov. Rhymbocarpus is shown to be a distinct leotialean genus, distinguished from Llimoniella by a different excipular structure, different pigments and the presence of excipular hairs, which, in some species, are embedded in the excipular gel and thus not visible macroscopically. In addition to the type species, R. geographici, of which a neotype is designated, it includes R. boomii sp. nov.,R. cruciatus comb, nov., R. fuscoatrae comb, nov.,R. makarovae sp. nov.,R. neglectus comb, nov., R. pertusariae sp. nov.,R. pubescens comb. nov. and R. stereocaulorum comb. nov. Llimoniella s. str. comprises at least 6 species, including the type, L. scabridula, L. adnata, L. pertusariae sp. nov., L. pyrenulae sp. nov., L. ramalinae comb. nov. and L. vinosa comb. nov. Several species formerly assigned to Skyttea or Llimoniella are now included in the leotialean genus Unguiculariopsis, and the following new combinations are proposed: Unguiculariopsis acrocordiae comb, nov., U. groenlandiae comb. nov. and U. lesdainii comb. nov. A lectotype is chosen for Lichen stictoceros, which is shown to be a synonym of Evemia prunastri. Keys are given for the species of Skyttea, Llimoniella and Rhymbocarpus, and for the lichenicolous genera of Leotiales and Ostropales.
Macrolichens of Montane Rain Forests in Panama, Province Chiriquí
Authors: Büdel Burkhard , Meyer Angelika , Salazar Noris , Zellner Hans , Zotz Gerhard , Lange Otto L.
Published: September 2002

Sixty-eight lichen species were found in the lower montane rain forest of Fortuna(1000-1200 m) in the province of Chiriquí, Panama; 33 of these were cyanobacterial lichens. The montane rain forest of the Volcan Bartú (2200-3100 m) yielded 30 species of lichens, 13 of which have cyanobacterial photobionts. Forty of the species reported are new records for Panama. Information concerning their habitats within the forest and their phytogeographical affinities is provided where possible.
Notes on Calicioid Lichens and Fungi from the Gongga Mountains (Sichuan, China)
Authors: Titov Alexander
Published: September 2002

Thirty-seven species of calicioid lichens and fungi are reported from the Gongga mountains (China). Chaenothecopsis tibellii and Phaeocalicium tibetanicum are described as new. The new combination Chaenothecopsis himalayensis (Räsänen).Tibell & Titov is proposed. A lectotype is selected for Mycocalicium himalayense Räsänen Chaenothecopsis nigropedata is reported as new to the Northern Hemisphere, Pyrgillus cubanus as new to Eurasia, and Chaenotheca cinerea new to Asia. Seven genera and 34 species are reported as new to China. Descriptions and illustrations of the new species are presented along with data on their habitat ecology and distribution.
Molecular and Morphological evolution in the Physciaceae (Lecanorales, Lichenized Ascomycotina), with Special Emphasis on the Genus Rinodina
Authors: Grube Martin , Arup Ulf
Published: September 2002

A phylogenetic hypothesis based on nuclear ITS sequence data is presented for the family Physciaceae based on various representatives of foliose and fruticose groups and a number of species selected from the crustose genera Rinodina and Buellia s.l. The analysis supports the monophyly of the Physcia- and the Buellia- groups. This is in agreement with existing morphological evidence, particularly ascus characters. The Physcia group in the analysis includes the genera Anaptychia, Heterodermia, Hyperphyscia, Mobergia, Phaeophyscia, Phaeorrhiza, Physcia, Physconia, Rinodina, and Rinodinella, while the Buellia group includes Amandinea, Buellia and Diploicia. The genera Physcia, Phaeophyscia, Phaeorrhiza and Rinodinella were well supported as monophyletic groups. The support for Physconia is low. Rinodina and Buellia are not supported as monophyletic genera. In agreement with ascus and ascospore characters, Buellia lindingeri is placed within the Rinodina group, close R. lecanorina. The genus Amandinea as currently circumscribed was not supported as a monophyletic group. The analysis confirms results from other lichen families that foliose members have evolved more than once from crustose lichens. Rinodina and Rinodinella species without chemical compounds in their thalli form the sister group to Phaeophyscia, and both groups form a monophyletic assemblage. A more detailed analysis of the Physcia group is presented. Whilst several of the foliose genera were well supported, there is only poor support for traditionally accepted crustose genera. The taxonomic implications of these findings are discussed.