bluuebunny/crossref_metadata_2025_split huggingface dataset:
Programmed, Autonomous‐Formal and Spontaneous Organizational Learning
Authors: Pak C. K. , Snell Robin S. 
Published: September 2003

AbstractOrganizational learning (OL) has been represented either as the systematic governance of collective expertise or as a relatively anarchic process of implicit transaction within and across fluid, dispersed communities of practice. Qualitative case‐study research open to both perspectives was conducted in a not‐for‐profit service organization, a franchisee company and a vertically integrated company, all based in Hong Kong. Two forms of OL as systematic governance were found: ‘programmed’ OL (POL) and ‘autonomous‐formal’ OL (AFOL), respectively. The relative emphasis on POL and AFOL appeared to vary from organization to organization, and to be influenced by management philosophy and by institutional frameworks such as professionalization and franchisee status. A ‘spontaneous’ and dispersed form of implicitly transacted OL (SOL) was also found. SOL appeared to reflect natural exuberance but was attenuated when colleagues regarded knowledge as a commodity. There appeared to be synergy between AFOL and SOL.
International Trade under Oligopoly Conditions
Authors: Ruffin Roy J. 
Published: September 2003

AbstractThe paper gives a simple representation of how oligopoly affects the general theory of international trade. Three points are emphasized: the simplicity of trade under oligopoly in the Ricardian model; the equations describing the general equilibrium of a world economy with any number of goods, countries, and factors under oligopolistic conditions and an integrated world market; and a complete description of the solution of a Mill–Ricardo–Cournot model with oligopoly in one sector and perfect competition in the other.
Anticipating Catastrophes through Extreme Value Modelling
Authors: Coles Stuart , Pericchi Luis 
Published: September 2003

SummaryWhen catastrophes strike it is easy to be wise after the event. It is also often argued that such catastrophic events are unforeseeable, or at least so implausible as to be negligible for planning purposes. We consider these issues in the context of daily rainfall measurements recorded in Venezuela. Before 1999 simple extreme value techniques were used to assess likely future levels of extreme rainfall, and these gave no particular cause for concern. In December 1999 a daily precipitation event of more than 410 mm, almost three times the magnitude of the previously recorded maximum, caused devastation and an estimated 30000 deaths. We look carefully at the previous history of the process and offer an extreme value analysis of the data—with some methodological novelty—that suggests that the 1999 event was much more plausible than the previous analyses had claimed. Deriving design parameters from the results of such an analysis may have had some mitigating effects on the consequences of the subsequent disaster. The themes of the new analysis are simple: the full exploitation of available data, proper accounting of uncertainty, careful interpretation of asymptotic limit laws and allowance for non-stationarity. The effect on the Venezuelan data analysis is dramatic. The broader implications are equally dramatic; that a naïve use of extreme value techniques is likely to lead to a false sense of security that might have devastating consequences in practice.
Variance Estimation for a Low Income Proportion
Authors: Berger Yves G. , Skinner Chris J. 
Published: September 2003

Summary
Proportions below a given fraction of a quantile of an income distribution are often estimated from survey data in comparisons of poverty. We consider the estimation of the variance of such a proportion, estimated from Family Expenditure Survey data. We show how a linearization method of variance estimation may be applied to this proportion, allowing for the effects of both a complex sampling design and weighting by a raking method to population controls. We show that, for data for 1998–1999, the estimated variances are always increased when allowance is made for the design and raking weights, the principal effect arising from the design. We also study the properties of a simplified variance estimator and discuss extensions to a wider class of poverty measures.
The DsbA Signal Sequence Directs Efficient, Cotranslational Export of Passenger Proteins to the
Escherichia coli
Periplasm via the Signal Recognition Particle Pathway
Authors: Schierle Clark F. , Berkmen Mehmet , Huber Damon , Kumamoto Carol , Boyd Dana , Beckwith Jon 
Published: September 2003

ABSTRACT

The
Escherichia coli
cytoplasmic protein thioredoxin 1 can be efficiently exported to the periplasmic space by the signal sequence of the DsbA protein (DsbAss) but not by the signal sequence of alkaline phosphatase (PhoA) or maltose binding protein (MBP). Using mutations of the signal recognition particle (SRP) pathway, we found that DsbAss directs thioredoxin 1 to the SRP export pathway. When DsbAss is fused to MBP, MBP also is directed to the SRP pathway. We show directly that the DsbAss-promoted export of MBP is largely cotranslational, in contrast to the mode of MBP export when the native signal sequence is utilized. However, both the export of thioredoxin 1 by DsbAss and the export of DsbA itself are quite sensitive to even the slight inhibition of SecA. These results suggest that SecA may be essential for both the slow posttranslational pathway and the SRP-dependent cotranslational pathway. Finally, probably because of its rapid folding in the cytoplasm, thioredoxin provides, along with gene fusion approaches, a sensitive assay system for signal sequences that utilize the SRP pathway.
Genome-Wide Analyses Revealing a Signaling Network of the RcsC-YojN-RcsB Phosphorelay System in
Escherichia coli
Authors: Hagiwara Daisuke , Sugiura Masahito , Oshima Taku , Mori Hirotada , Aiba Hirofumi , Yamashino Takafumi , Mizuno Takeshi 
Published: September 2003

ABSTRACT

In
Escherichia coli
, capsular colanic acid polysaccharide synthesis is regulated through the multistep RcsC→YojN→RcsB phosphorelay. By monitoring a hallmarked
cps
::
lacZ
reporter gene, we first searched for physiological stimuli that propagate the Rcs signaling system. The expression of
cps
::
lacZ
was activated when cells were grown at a low temperature (20°C) in the presence of glucose as a carbon source and in the presence of a relatively high concentration of external zinc (1 mM ZnCl
2
). In this Rcs signaling system, the
rcsF
gene product (a putative outer membrane-located lipoprotein) was also an essential signaling component. Based on the defined signaling pathway and physiological stimuli for the Rcs signaling system, we conducted genome-wide analyses with microarrays to clarify the Rcs transcriptome (i.e., Rcs regulon). Thirty-two genes were identified as putative Rcs regulon members; these genes included 15 new genes in addition to 17 of the previously described
cps
genes. Using a set of 37 two-component system mutants, we performed alternative genome-wide analyses. The results showed that the propagation of the zinc-responsive Rcs signaling system was largely dependent on another two-component system, PhoQ/P. Considering the fact that the PhoQ/P signaling system responds to external magnesium, we obtained evidence which supports the view that there is a signaling network that connects the Rcs system with the PhoQ/P system, which coordinately regulates extracellular polysaccharide synthesis in response to the external concentrations of divalent cations.
Characterization of a Spontaneous Nonmagnetic Mutant ofMagnetospirillum gryphiswaldenseReveals a Large Deletion Comprising a Putative Magnetosome Island
Authors: Schübbe Sabrina , Kube Michael , Scheffel André , Wawer Cathrin , Heyen Udo , Meyerdierks Anke , Madkour Mohamed H. , Mayer Frank , Reinhardt Richard , Schüler Dirk 
Published: September 2003

ABSTRACTFrequent spontaneous loss of the magnetic phenotype was observed in stationary-phase cultures of the magnetotactic bacteriumMagnetospirillum gryphiswaldenseMSR-1. A nonmagnetic mutant, designated strain MSR-1B, was isolated and characterized. The mutant lacked any structures resembling magnetosome crystals as well as internal membrane vesicles. The growth of strain MSR-1B was impaired under all growth conditions tested, and the uptake and accumulation of iron were drastically reduced under iron-replete conditions. A large chromosomal deletion of approximately 80 kb was identified in strain MSR-1B, which comprised both the entiremamABandmamDCclusters as well as further putative operons encoding a number of magnetosome-associated proteins. A bacterial artificial chromosome clone partially covering the deleted region was isolated from the genomic library of wild-typeM. gryphiswaldense. Sequence analysis of this fragment revealed that all previously identifiedmamgenes were closely linked with genes encoding other magnetosome-associated proteins within less than 35 kb. In addition, this region was remarkably rich in insertion elements and harbored a considerable number of unknown gene families which appeared to be specific for magnetotactic bacteria. Overall, these findings suggest the existence of a putative large magnetosome island inM. gryphiswaldenseand other magnetotactic bacteria.
Role of 2-Phosphoglycolate Phosphatase ofEscherichia coliin Metabolism of the 2-Phosphoglycolate Formed in DNA Repair
Authors: Pellicer Maria Teresa , Nuñez Maria Felisa , Aguilar Juan , Badia Josefa , Baldoma Laura 
Published: September 2003

ABSTRACTThe enzyme 2-phosphoglycolate phosphatase fromEscherichia coli, encoded by thegphgene, was purified and characterized. The enzyme was highly specific for 2-phosphoglycolate and showed good catalytic efficiency (kcat/Km), which enabled the conversion of this substrate even at low intracellular concentrations. A comparison of the structural and functional features of this enzyme with those of 2-phosphoglycolate phosphatases of different origins showed a high similarity of the sequences, implying the use of the same catalytic mechanism. Western blot analysis revealed constitutive expression of thegphgene, regardless of the carbon source used, growth stage, or oxidative stress conditions. We showed that this housekeeping enzyme is involved in the dissimilation of the intracellular 2-phosphoglycolate formed in the DNA repair of 3′-phosphoglycolate ends. DNA strand breaks of this kind are caused by agents such as the radiomimetic compound bleomycin. The differential response between a 2-phosphoglycolate phosphatase-deficient mutant and its parental strain after treatment with bleomycin allowed us to connect the intracellular formation of 2-phosphoglycolate with the production of glycolate, which is subsequently incorporated into general metabolism. We thus provide evidence for a salvage function of 2-phosphoglycolate phosphatase in the metabolism of a two-carbon compound generated by the cellular DNA repair machinery.
Complete Sequence of Virulence Plasmid pJM1 from the Marine Fish PathogenVibrio anguillarumStrain 775
Authors: Di Lorenzo Manuela , Stork Michiel , Tolmasky Marcelo E. , Actis Luis A. , Farrell David , Welch Timothy J. , Crosa Lidia M. , Wertheimer Anne M. , Chen Qian , Salinas Patricia , Waldbeser Lillian , Crosa Jorge H. 
Published: September 2003

ABSTRACTThe virulence plasmid pJM1 enables the fish pathogenVibrio anguillarum, a gram-negative polarly flagellated comma-shaped rod bacterium, to cause a highly fatal hemorrhagic septicemic disease in salmonids and other fishes, leading to epizootics throughout the world. The pJM1 plasmid 65,009-nucleotide sequence, with an overall G+C content of 42.6%, revealed genes and open reading frames (ORFs) encoding iron transporters, nonribosomal peptide enzymes, and other proteins essential for the biosynthesis of the siderophore anguibactin. Of the 59 ORFs, approximately 32% were related to iron metabolic functions. The plasmid pJM1 confers onV. anguillarumthe ability to take up ferric iron as a complex with anguibactin from a medium in which iron is chelated by transferrin, ethylenediamine-di(o-hydroxyphenyl-acetic acid), or other iron-chelating compounds. ThefatDCBA-angRToperon as well as other downstream biosynthetic genes is bracketed by the homologous ISV-A1 and ISV-A2 insertion sequences. Other clusters on the plasmid also show an insertion element-flanked organization, including ORFs homologous to genes involved in the biosynthesis of 2,3-dihydroxybenzoic acid. Homologues of replication and partition genes are also identified on pJM1 adjacent to this region. ORFs with no known function represent approximately 30% of the pJM1 sequence. The insertion sequence elements in the composite transposon-like structures, corroborated by the G+C content of the pJM1 sequence, suggest a modular composition of plasmid pJM1, biased towards acquisition of modules containing genes related to iron metabolic functions. We also show that there is considerable microheterogeneity in pJM1-like plasmids from virulent strains ofV. anguillarumisolated from different geographical sources.
Monomeric NarB Is a Dual-Affinity Nitrate Reductase, and Its Activity Is Regulated Differently from That of Nitrate Uptake in the Unicellular Diazotrophic Cyanobacterium
Synechococcus
sp. Strain RF-1
Authors: Wang Tung-Hei , Fu Hongyong , Shieh Yuh-Jang 
Published: September 2003

ABSTRACT

Synechococcus
sp. strain RF-1 is a unicellular freshwater cyanobacterium that fixes N
2
aerobically and exhibits a circadian rhythm for nitrogenase activity under a light-dark regimen.
Synechococcus
sp. strain RF-1 also utilizes nitrate, nitrite, or ammonium for growth. Under the diazotrophic growth, the nitrate uptake in
Synechococcus
sp. strain RF-1 was induced by nitrate or nitrite but repressed by ammonium. In contrast, a prominent nitrate reductase (NR) activity was detected in diazotrophically grown cells using the reduced methyl viologen assay. The NR activity was not inhibited by ammonium and only slightly enhanced by nitrate. The different expression patterns of nitrate uptake and NR in
Synechococcus
sp. strain RF-1 were reflected in general at the transcript level determined by reverse transcriptase PCR. Under both nitrate-induced and uninduced conditions, the in situ NR activity exhibited similar biphasic kinetics for nitrate. The recombinant NR encoded by the
narB
gene of
Synechococcus
sp. strain RF-1, expressed in
E. coli
, also showed the biphasic kinetics with similar pH and temperature profiles. By in-gel NR activity assay, the recombinant NarB was found to exist as a single form. Both the high- and low-affinity NR activities of the recombinant NarB showed the same thermostability. When modified at the N terminus by a polyhistidine tag, the recombinant NR activity was shifted from biphasic to hyperbolic kinetics and showed only a single

K
m

for nitrate, indicating the functional importance of the NarB N-terminal structure in NR kinetics.
Identification of genes modulated in multiple myeloma using genetically identical twin samples
Authors: Munshi Nikhil C. , Hideshima Teru , Carrasco Daniel , Shammas Masood , Auclair Daniel , Davies Faith , Mitsiades Nicholas , Mitsiades Constantine , Kim Ryung Suk , Li Cheng , Rajkumar S. Vincent , Fonseca Rafael , Bergsagel Lief , Chauhan Dharminder , Anderson Kenneth C. 
Published: September 2003

AbstractGenetic heterogeneity between individuals confounds the comparison of gene profiling of multiple myeloma (MM) cells versus normal plasma cells (PCs). To overcome this barrier, we compared the gene expression profile of CD138+ MM cells from a patient bone marrow (BM) sample with CD138+ PCs from a genetically identical twin BM sample using microarray profiling. Two hundred and ninety-six genes were up-regulated and 103 genes were down-regulated at least 2-fold in MM cells versus normal twin PCs. Highly expressed genes in MM cells included cell survival pathway genes such as mcl-1, dad-1, caspase 8, and FADD-like apoptosis regulator (FLIP); oncogenes/transcriptional factors such as Jun-D, Xbp-1, calmodulin, Calnexin, and FGFR-3; stress response and ubiquitin/proteasome pathway–related genes and various ribosomal genes reflecting increased metabolic and translational activity. Genes that were down-regulated in MM cells versus healthy twin PCs included RAD51, killer cell immunoglobulin-like receptor protein, and apoptotic protease activating factor. Microarray results were further confirmed by Western blot analyses, immunohistochemistry, fluorescent in situ hybridization (FISH), and functional assays of telomerase activity and bone marrow angiogenesis. This molecular profiling provides potential insights into mechanisms of malignant transformation in MM. For example, FGFR3, xbp-1, and both mcl-1 and dad-1 may mediate transformation, differentiation, and survival, respectively, and may have clinical implications. By identifying genes uniquely altered in MM cells compared with normal PCs in an identical genotypic background, the current study provides the framework to identify novel therapeutic targets.
Safety and efficacy of factor IX gene transfer to skeletal muscle in murine and canine hemophilia B models by adeno-associated viral vector serotype 1
Authors: Arruda Valder R. , Schuettrumpf Joerg , Herzog Roland W. , Nichols Timothy C. , Robinson Nancy , Lotfi Yasmin , Mingozzi Federico , Xiao Weidong , Couto Linda B. , High Katherine A. 
Published: September 2003

Abstract
Adeno-associated viral (AAV) vectors (serotype 2) efficiently transduce skeletal muscle, and have been used as gene delivery vehicles for hemophilia B and for muscular dystrophies in experimental animals and humans. Recent reports suggest that AAV vectors based on serotypes 1, 5, and 7 transduce murine skeletal muscle much more efficiently than AAV-2, with reported increases in expression ranging from 2-fold to 1000-fold. We sought to determine whether this increased efficacy could be observed in species other than mice. In immunodeficient mice we saw 10- to 20-fold higher levels of human factor IX (hF.IX) expression at a range of doses, and in hemophilic dogs we observed approximately 50-fold higher levels of expression. The increase in transgene expression was due partly to higher gene copy number and a larger number of cells transduced at each injection site. In all immunocompetent animals injected with AAV-1, inhibitory antibodies to F.IX developed, but in immunocompetent mice treated with high doses of vector, inhibitory antibodies eventually disappeared. These studies emphasize that the increased efficacy of AAV-1 vectors carries a risk of inhibitor formation, and that further studies will be required to define doses and treatment regimens that result in tolerance rather than immunity to F.IX.
Survivin regulates hematopoietic progenitor cell proliferation through p21WAF1/Cip1-dependent and -independent pathways
Authors: Fukuda Seiji , Mantel Charlie R. , Pelus Louis M. 
Published: September 2003

AbstractThe cyclin-dependent kinase inhibitor p21WAF1/Cip1 and Survivin enhance granulocyte macrophage colony-forming unit (CFU-GM) cell cycle and proliferation and have been implicated as antiapoptotic proteins. We investigated the relationships between p21 and Survivin in primary CFU-GM and c-kit+, lineage-negative (Lin–) cells and demonstrate p21-dependent and -independent pathways whereby Survivin regulates progenitor cell proliferation. Ectopic Survivin enhanced p21+/+ CFU-GM formation and expansion of c-kit+, Lin– cells, whereas p21 gene loss abrogated these effects, indicating a p21 requirement. A dominant-negative form of Survivin and p21 gene deletion accelerated the loss of CFU-GM upon growth factor deprivation, and wild-type Survivin overexpression inhibited apoptosis of p21+/+ CFU-GM and c-kit+, Lin– cells but not p21–/– cells, suggesting that both Survivin and p21 block apoptosis of progenitors and that Survivin-mediated antiapoptosis requires p21. In contrast to the p21-dependent antiapoptotic effects, Survivin increased the proportion of CFU-GM in S-phase in both p21+/+ and p21–/– cells. Furthermore, modulating Survivin expression increased polyploidy in c-kit+, Lin– cells, which was accentuated by p21 deficiency. These results suggest that the Survivin-p21 axis plays an important role in the proliferation of normal hematopoietic cells and that Survivin regulates apoptosis through a p21 WAF1/Cip1-dependent pathway but may control S-phase entry independent of p21.
Ligation of CD137 receptor prevents and reverses established anergy of CD8+ cytolytic T lymphocytes in vivo
Authors: Wilcox Ryan A. , Tamada Koji , Flies Dallas B. , Zhu Gefeng , Chapoval Andrei I. , Blazar Bruce R. , Kast W. Martin , Chen Lieping 
Published: September 2003

AbstractT-cell anergy is a tolerance mechanism defined as a hyporesponsive status of antigen-specific T cells upon prior antigen encounter and is believed to play a critical role in the evasion of tumor immunity and the amelioration of allogeneic transplant rejection. Molecular mechanisms in controlling T-cell anergy are less known. We show here that administration of an agonistic monoclonal antibody (mAb) to CD137, a member of the tumor necrosis factor receptor superfamily, prevents the induction of CD8+ cytolytic T-lymphocyte (CTL) anergy by soluble antigens. More importantly, CD137 mAb restores the functions of established anergic CTLs upon reencountering their cognate antigen. As a result, infusion of CD137 mAb inhibits progressive tumor growth that is caused by soluble tumor antigen-induced tolerance in a P815R model. CD137 mAb also restores proliferation and effector functions of anergic alloreactive 2C T cells in a bone marrow transplantation model. Our results indicate that ligation of CD137 receptor delivers a regulatory signal for T-cell anergy and implicate manipulation of the CD137 pathway as a new approach to break T-cell tolerance.
Female donors contribute to a selective graft-versus-leukemia effect in male recipients of HLA-matched, related hematopoietic stem cell transplants
Authors: Randolph Sophia S. B. , Gooley Theodore A. , Warren Edus H. , Appelbaum Frederick R. , Riddell Stanley R. 
Published: September 2003

Abstract
Male recipients of transplants from female (F→M) hematopoietic stem cell donors represent a special group in whom donor T cells that are specific for recipient minor histocompatibility antigens encoded by Y-chromosome genes may contribute to a graft-versus-leukemia (GVL) effect and to graft-versus-host disease (GVHD). We examined the contribution of donor/patient sex to the risk for relapse and GVHD in 3238 patients who underwent HLA-identical sibling hematopoietic stem cell transplantation (HSCT) for hematopoietic malignancies at a single institution. Compared with other sex combinations, male recipients of female transplants had the lowest risk for relapse and the greatest odds for GVHD. Remarkably, after controlling for GVHD as a time-dependent covariate, F→M HSCT still exhibited a lower risk for relapse than other sex combinations, demonstrating a selective GVL effect distinct from that contributed by GVHD. A reduction in relapse after F→M HSCT was observed in patients with chronic myelogenous leukemia (CML), acute myelogenous leukemia (AML), and acute lymphoblastic leukemia (ALL). Taken together, these data suggest that minor H antigens encoded or regulated by genes on the Y chromosome contribute to a selective GVL effect against myeloid and lymphoid leukemias after F→M HSCT.