bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dimension reduction and graphical exploration in regression including survival analysis
Authors: Cook R. Dennis 
Published: April 2003

AbstractRecent advances in dimension reduction and visualization can greatly facilitate the exploratory and diagnostic stages of a regression analysis. This paper contains an expository discussion of selected methodology that came from these advances. Various applications are described, including new results on survival regressions with censoring. All of the methodology described in this paper is available in Arc, a recently released computer program that integrates many standard regression methods with recent developments in regression graphics. Arc implementations are indicated throughout the discussion. Copyright © 2003 John Wiley & Sons, Ltd.
An investigation of error sources and their impact in estimating the time to the most recent ancestor of spatially and temporally distributed HIV sequences
Authors: Burr Tom L. , Gattiker James R. , Gerrish Philip J. 
Published: April 2003

AbstractThis is an investigation of significant error sources and their impact in estimating the time to the most recent common ancestor (MRCA) of spatially and temporally distributed human immunodeficiency virus (HIV) sequences. We simulate an HIV epidemic under a range of assumptions with known time to the MRCA (tMRCA). We then apply a range of baseline (known) evolutionary models to generate sequence data. We next estimate or assume one of several misspecified models and use the chosen model to estimate the time to the MRCA. Random effects and the extent of model misspecification determine the magnitude of error sources that could include: neglected heterogeneity in substitution rates across lineages and DNA sites; uncertainty in HIV isolation times; uncertain magnitude and type of population subdivision; uncertain impacts of host/viral transmission dynamics, and unavoidable model estimation errors. Our results suggest that confidence intervals will rarely have the nominal coverage probability for tMRCA. Neglected effects lead to errors that are unaccounted for in most analyses, resulting in optimistically narrow confidence intervals (CI). Using real HIV sequences having approximately known isolation times and locations, we present possible confidence intervals for several sets of assumptions. In general, we cannot be certain how much to broaden a stated confidence interval for tMRCA. However, we describe the impact of candidate error sources on CI width. We also determine which error sources have the most impact on CI width and demonstrate that the standard bootstrap method will underestimate the CI width. Copyright © 2003 John Wiley & Sons, Ltd.
Bayesian analysis of quantitative antimicrobial assays
Authors: Varbanov Alex R. , Taylor Charles H. 
Published: April 2003

AbstractQuantitative antimicrobial assays are used to assess the efficacy of chemical germicides. Standard methods for statistical analysis use log reduction (LR), the difference on the log scale between average surviving microbes for control and test carriers, as an efficacy measure. These methods have several deficiencies. The LR parameter is not on the original response scale, which complicates its interpretation. The presence of two different definitions of LR makes the statistical inference even more difficult. Current statistical methods for antimicrobial assay analysis rely on asymptotic normal theory, which might not work well for small samples. In addition, they do not appropriately incorporate censored (‘too numerous to be counted’) observations in the analysis. To overcome those problems, a new Bayesian approach is introduced here. It has also the advantages of more flexible statistical inference, and incorporated prior information in the model. Copyright © 2003 John Wiley & Sons, Ltd.
Sampling minority groups in health surveys
Authors: Kalsbeek William D. 
Published: April 2003

AbstractSampling racial and ethnic minority groups in population‐based health studies presents the statistical designer with a variety of notable challenges, many of which can be traced to the manner in which the sampling frame maps into the set of group members. A brief review of sampling approaches aimed at race/ethnic groups is followed by findings on two particularly important statistical issues one may face when sampling minorities: the implications of the geographic diffusion of minorities within sampled area clusters, and the relative utility of different forms of space and time sampling to deal with sometimes dramatic change over time in the linkage between entries on a sampling frame and members of relatively mobile minority groups. Simulated findings from practical illustrations involving the sampling of Hispanics are presented to address each issue. Copyright © 2003 John Wiley & Sons, Ltd.
Spatial prediction of counts and rates
Authors: Gotway Carol A. , Wolfinger Russell D. 
Published: April 2003

AbstractIn this paper we provide both theoretical and empirical comparisons of marginal and conditional methods for analysing spatial count data. We focus on methods for spatial prediction developed from a generalized linear mixed model framework and compare them with the traditional linear (kriging) predictor. Prediction methods are illustrated and compared through a case study based on real data and through a detailed simulation study. The paper emphasizes a better understanding of the strengths and weaknesses of each approach. Published in 2003 by John Wiley & Sons, Ltd.
Seizing the moment: scientists' authorship rights in the digital age
Authors: Frankel Mark S. 
Published: April 2003

ABSTRACTThe American Association for the Advancement of Science carried out a study on intellectual property and electronic journal publishing with the aim of identifying those aspects of the intellectual property regime that facilitate or constrain the effective development of electronic scientific publishing. This paper summarizes the conclusions reached, emphasizes the continuing need to maintain the legal framework offered by copyright law, but makes recommendations both for its modification and in its application to ensure that the potential benefits of electronic publishing are fully realized.The full report by AAAS is posted on the Web at www.aaas.org/spp/sfrl/projects/epub/finalrept.html
BioOne: building a sustainable alternative publishing model for non‐profit publishers
Authors: Joseph Heather Dalterio 
Published: April 2003

ABSTRACTAn account is given of the difficulties caused to smaller learned publishers and to the academic library system in the move to electronic delivery of results of scientific and medical research. BioOne, a co‐operative venture of such publishers and libraries, is then described with an account of its progress to date.
Use of In-Biofilm Expression Technology To Identify Genes Involved in
Pseudomonas aeruginosa
Biofilm Development
Authors: Finelli Antonio , Gallant Claude V. , Jarvi Keith , Burrows Lori L. 
Published: April 2003

ABSTRACT

Mature
Pseudomonas aeruginosa
biofilms form complex three-dimensional architecture and are tolerant of antibiotics and other antimicrobial compounds. In this work, an in vivo expression technology system, originally designed to study virulence-associated genes in complex mammalian environments, was used to identify genes up-regulated in
P. aeruginosa
grown to a mature (5-day) biofilm. Five unique cloned promoters unable to promote in vitro growth in the absence of purines after recovery from the biofilm environment were identified. The open reading frames downstream of the cloned promoter regions were identified, and knockout mutants were generated. Insertional mutation of PA5065, a homologue of
Escherichia coli ubiB
, was lethal, while inactivation of PA0240 (a porin homologue), PA3710 (a putative alcohol dehydrogenase), and PA3782 (a homologue of the
Streptomyces griseus
developmental regulator
adpA
) had no effect on planktonic growth but caused defects in biofilm formation in static and flowing systems. In competition experiments, mutants demonstrated reduced fitness compared with the parent strain, comprising less than 0.0001% of total biofilm cells after 5 days. Therefore, using in-biofilm expression technology, we have identified novel genes that do not affect planktonic growth but are important for biofilm formation, development, and fitness.
Chaperone-Subunit-Usher Interactions Required for Donor Strand Exchange during Bacterial Pilus Assembly
Authors: Barnhart Michelle M. , Sauer Frederic G. , Pinkner Jerome S. , Hultgren Scott J. 
Published: April 2003

ABSTRACT

The assembly of type 1 pili on the surface of uropathogenic
Escherichia coli
proceeds via the chaperone-usher pathway. Chaperone-subunit complexes interact with one another via a process termed donor strand complementation whereby the G1β strand of the chaperone completes the immunoglobulin (Ig) fold of the pilus subunit. Chaperone-subunit complexes are targeted to the usher, which forms a channel across the outer membrane through which pilus subunits are translocated and assembled into pili via a mechanism known as donor strand exchange. This is a mechanism whereby chaperone uncapping from a subunit is coupled with the simultaneous assembly of the subunit into the pilus fiber. Thus, in the pilus fiber, the N-terminal extension of every subunit completes the Ig fold of its neighboring subunit by occupying the same site previously occupied by the chaperone. Here, we investigated details of the donor strand exchange assembly mechanism. We discovered that the information necessary for targeting the FimC-FimH complex to the usher resides mainly in the FimH protein. This interaction is an initiating event in pilus biogenesis. We discovered that the ability of an incoming subunit (in a chaperone-subunit complex) to participate in donor strand exchange with the growing pilus depended on a previously unrecognized function of the chaperone. Furthermore, the donor strand exchange assembly mechanism between subunits was found to be necessary for subunit translocation across the outer membrane usher.
Natural Variation in the Microcystin Synthetase Operon
mcyABC
and Impact on Microcystin Production in
Microcystis
Strains
Authors: Mikalsen Bjørg , Boison Gudrun , Skulberg Olav M. , Fastner Jutta , Davies William , Gabrielsen Tove M. , Rudi Knut , Jakobsen Kjetill S. 
Published: April 2003

ABSTRACT

Toxic
Microcystis
strains often produce several isoforms of the cyclic hepatotoxin microcystin, and more than 65 isoforms are known. This has been attributed to relaxed substrate specificity of the adenylation domain. Our results show that in addition to this, variability is also caused by genetic variation in the microcystin synthetase genes. Genetic characterization of a region of the adenylation domain in module
mcyB1
resulted in identification of two groups of genetic variants in closely related
Microcystis
strains. Sequence analyses suggested that the genetic variation is due to recombination events between
mcyB1
and the corresponding domains in
mcyC
. Each variant could be correlated to a particular microcystin isoform profile, as identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry. Among the
Microcystis
species studied, we found 11 strains containing different variants of the
mcyABC
gene cluster and 7 strains lacking the genes. Furthermore, there is no concordance between the phylogenies generated with
mcyB1
, 16S ribosomal DNA, and DNA fingerprinting. Collectively, these results suggest that recombination between imperfect repeats, gene loss, and horizontal gene transfer can explain the distribution and variation within the
mcyABC
operon.
Characterization of Chlorophenol 4-Monooxygenase (TftD) and NADH:Flavin Adenine Dinucleotide Oxidoreductase (TftC) of
Burkholderia cepacia
AC1100
Authors: Gisi Michelle R. , Xun Luying 
Published: April 2003

ABSTRACT

Burkholderia cepacia
AC1100 uses 2,4,5-trichlorophenoxyacetic acid, an environmental pollutant, as a sole carbon and energy source. Chlorophenol 4-monooxygenase is a key enzyme in the degradation of 2,4,5-trichlorophenoxyacetic acid, and it was originally characterized as a two-component enzyme (TftC and TftD). Sequence analysis suggests that they are separate enzymes. The two proteins were separately produced in
Escherichia coli
, purified, and characterized. TftC was an NADH:flavin adenine dinucleotide (FAD) oxidoreductase. A C-terminally His-tagged fusion TftC used NADH to reduce either FAD or flavin mononucleotide (FMN) but did not use NADPH or riboflavin as a substrate. Kinetic and binding property analysis showed that FAD was a better substrate than FMN. TftD was a reduced FAD (FADH
2
)-utilizing monooxygenase, and FADH
2
was supplied by TftC. It converted 2,4,5-trichlorophenol to 2,5-dichloro-
p
-quinol and then to 5-chlorohydroxyquinol but converted 2,4,6-trichlorophenol only to 2,6-dichloro-
p
-quinol as the final product. TftD interacted with FADH
2
and retarded its rapid oxidation by O
2
. A spectrum of possible TftD-bound FAD-peroxide was identified, indicating that the peroxide is likely the active oxygen species attacking the aromatic substrates. The reclassification of the two enzymes further supports the new discovery of FADH
2
-utilizing enzymes, which have homologues in the domains
Bacteria
and
Archaea
.
Genetic Analysis of Pathway Specificity during Posttranslational Protein Translocation across the
Escherichia coli
Plasma Membrane
Authors: Blaudeck Natascha , Kreutzenbeck Peter , Freudl Roland , Sprenger Georg A. 
Published: April 2003

ABSTRACT

In
Escherichia coli
, the SecB/SecA branch of the Sec pathway and the twin-arginine translocation (Tat) pathway represent two alternative possibilities for posttranslational translocation of proteins across the cytoplasmic membrane. Maintenance of pathway specificity was analyzed using a model precursor consisting of the mature part of the SecB-dependent maltose-binding protein (MalE) fused to the signal peptide of the Tat-dependent TorA protein. The TorA signal peptide selectively and specifically directed MalE into the Tat pathway. The characterization of a spontaneous TorA signal peptide mutant (TorA*), in which the two arginine residues in the c-region had been replaced by one leucine residue, showed that the TorA*-MalE mutant precursor had acquired the ability for efficiently using the SecB/SecA pathway. Despite the lack of the “Sec avoidance signal,” the mutant precursor was still capable of using the Tat pathway, provided that the kinetically favored Sec pathway was blocked. These results show that the h-region of the TorA signal peptide is, in principle, sufficiently hydrophobic for Sec-dependent protein translocation, and therefore, the positively charged amino acid residues in the c-region represent a major determinant for Tat pathway specificity. Tat-dependent export of TorA-MalE was significantly slower in the presence of SecB than in its absence, showing that SecB can bind to this precursor despite the presence of the Sec avoidance signal in the c-region of the TorA signal peptide, strongly suggesting that the function of the Sec avoidance signal is not the prevention of SecB binding; rather, it must be exerted at a later step in the Sec pathway.
Growth Rate-Dependent Regulation of Medial FtsZ Ring Formation
Authors: Weart Richard B. , Levin Petra Anne 
Published: April 2003

ABSTRACTFtsZ is an essential cell division protein conserved throughout the bacteria and archaea. In response to an unknown cell cycle signal, FtsZ polymerizes into a ring that establishes the future division site. We conducted a series of experiments examining the link between growth rate, medial FtsZ ring formation, and the intracellular concentration of FtsZ in the gram-positive bacteriumBacillus subtilis.We found that, although the frequency of cells with FtsZ rings varies as much as threefold in a growth rate-dependent manner, the average intracellular concentration of FtsZ remains constant irrespective of doubling time. Additionally, expressingftsZsolely from a constitutive promoter, thereby eliminating normal transcriptional control, did not alter the growth rate regulation of medial FtsZ ring formation. Finally, our data indicate that overexpressing FtsZ does not dramatically increase the frequency of cells with medial FtsZ rings, suggesting that the mechanisms governing ring formation are refractile to increases in FtsZ concentration. These results support a model in which the timing of FtsZ assembly is governed primarily through cell cycle-dependent changes in FtsZ polymerization kinetics and not simply via oscillations in the intracellular concentration of FtsZ. Importantly, this model can be extended to the gram-negative bacteriumEscherichia coli. Our data show that, like those inB. subtilis, average FtsZ levels inE. coliare constant irrespective of doubling time.
Identification of the DNA Binding Sites of PerA, the Transcriptional Activator of thebfpandperOperons in EnteropathogenicEscherichia coli
Authors: Ibarra J. Antonio , Villalba Miryam I. , Puente José Luis 
Published: April 2003

ABSTRACTThe bundle-forming pilus (BFP) is an important virulence factor for enteropathogenicEscherichia coli(EPEC). Genes involved in its biogenesis and regulation are tightly regulated by PerA (BfpT), a member of the AraC/XylS family of transcriptional regulators. The aim of this work was to purify PerA and determine its association withbfpAandperA(bfpT) regulatory regions by electrophoretic mobility shift and DNase I footprinting assays. PerA was purified as a maltose-binding protein (MBP) fusion, which was capable of complementingbfpAexpression and which was able to restore the localized adherence phenotype of an EPECperAmutant strain. Upstream ofbfpAandperA, MBP-PerA recognized with similar affinity asymmetric nucleotide sequences in which a 29-bp-long AT-rich consensus motif was identified. These DNA motifs share 66% identity and were previously shown, by deletion analysis, to be involved in the PerA-dependent expression of both genes. Interestingly, inperA, this motif spans the sequence between positions −75 and −47, approximately one helix turn upstream of the −35 promoter sequence, while inbfpA, it spans the sequence between positions −83 and −55, approximately two helix turns upstream from the promoter. An additional PerA binding site was identified at the 5′ end of thebfpAstructural gene, which was not required for its activation. Experiments with LexA-PerA fusions suggested that PerA acts as a monomer to activate the transcription of bothperAandbfpA, in contrast to what has been documented for other members of this family of transcriptional regulators.
Involvement of the
adc
Operon and Manganese Homeostasis in
Streptococcus gordonii
Biofilm Formation
Authors: Loo C. Y. , Mitrakul K. , Voss I. B. , Hughes C. V. , Ganeshkumar N. 
Published: April 2003

ABSTRACT

Pioneer oral bacteria, including
Streptococcus gordonii
, initiate the formation of oral biofilms on tooth surfaces, which requires differential expression of genes that recognize unique environmental cues. An
S. gordonii
::Tn
917-lac
biofilm-defective mutant was isolated by using an in vitro biofilm formation assay. Subsequent inverse PCR and sequence analyses identified the transposon insertion to be near the 3′ end of an open reading frame (ORF) encoding a protein homologous to a
Streptococcus pneumoniae
repressor, AdcR. The
S. gordonii adc
operon, consisting of the four ORFs
adcR
,
adcC
,
adcB
, and
adcA
, is homologous to the
adc
operon of
S. pneumoniae
, which plays a role in zinc and/or manganese transport and genetic competence in
S. pneumoniae
. AdcR is a metal-dependent repressor protein containing a putative metal-binding site, AdcC contains a consensus-binding site for ATP, AdcB is a hydrophobic protein with seven hydrophobic membrane-spanning regions, and AdcA is a lipoprotein permease with a putative metal-binding site. The three proteins (AdcC through -A) are similar to those of the binding-lipoprotein-dependent transport system of gram-positive bacteria. Reverse transcriptase PCR confirmed that
adcRCBA
are cotranscribed as an operon in
S. gordonii
and that the transposon insertion in
S. gordonii adcR
::Tn
917-lac
had resulted in a polar mutation. Expression of
adcR
, measured by the β-galactosidase activity of the
adcR
::Tn
917-lac
mutant, was growth phase dependent and increased when the mutant was grown in media with high levels of manganese (>1 mM) and to a lesser extent in media with zinc, indicating that AdcR may be a regulator at high levels of extracellular manganese. A nonpolar inactivation of
adcR
generated by allelic replacement resulted in a biofilm- and competence-defective phenotype. The biofilm-defective phenotype observed suggests that AdcR is an active repressor when synthesized and acts at a distant site(s) on the chromosome. Thus, the
adc
operon is involved in manganese acquisition in
S. gordonii
and manganese homeostasis and appears to modulate sessile growth in this bacterium.
The YSIRK-G/S Motif of Staphylococcal Protein A and Its Role in Efficiency of Signal Peptide Processing
Authors: Bae Taeok , Schneewind Olaf 
Published: April 2003

ABSTRACTMany surface proteins of pathogenic gram-positive bacteria are linked to the cell wall envelope by a mechanism requiring a C-terminal sorting signal with an LPXTG motif. Surface proteins ofStreptococcus pneumoniaeharbor another motif, YSIRK-G/S, which is positioned within signal peptides. The signal peptides of some, but not all, of the 20 surface proteins ofStaphylococcus aureuscarry a YSIRK-G/S motif, whereas those of surface proteins ofListeria monocytogenesandBacillus anthracisdo not. To determine whether the YSIRK-G/S motif is required for the secretion or cell wall anchoring of surface proteins, we analyzed variants of staphylococcal protein A, an immunoglobulin binding protein with an LPXTG sorting signal. Deletion of the YSIR sequence or replacement of G or S significantly reduced the rate of signal peptide processing of protein A precursors. In contrast, cell wall anchoring or the functional display of protein A was not affected. The fusion of cell wall sorting signals to reporter proteins bearing N-terminal signal peptides with or without the YSIRK-G/S motif resulted in hybrid proteins that were anchored in a manner similar to that of wild-type protein A. The requirement of the YSIRK-G/S motif for efficient secretion implies the existence of a specialized mode of substrate recognition by the secretion pathway of gram-positive cocci. It seems, however, that this mechanism is not essential for surface protein anchoring to the cell wall envelope.
Species-Wide Variation in the
Escherichia coli
Flagellin (H-Antigen) Gene
Authors: Wang Lei , Rothemund Deborah , Curd Heather , Reeves Peter R. 
Published: April 2003

ABSTRACT

Escherichia coli
is a clonal species. The best-understood components of its clonal variation are the flagellar (H) and polysaccharide (O) antigens, both well documented since the mid-1930s because of their use in serotyping. Flagellin is the protein subunit of the flagellum that carries H-antigen specificity. We show that 43 of the 54 H-antigen specificities of
E. coli
map to the flagellin gene at
fliC
and sequenced all 43 forms and confirmed specificity of each by cloning and expression. This is, to our knowledge, the first time that all known forms of such a highly polymorphic gene have been fully sequenced and characterized for any species. The established distinction between a highly variable central region and more conserved flanking regions is upheld. The sequences fall into two groups, one of which may be derived from the
fliC
gene of the
E. coli
/
Salmonella enterica
common ancestor, the other perhaps obtained by lateral transfer since species divergence. Comparison of sequences revealed that both horizontal DNA transfer and fixation of mutations under diversifying selection pressure contributed to polymorphism in this locus.