bluuebunny/crossref_metadata_2025 huggingface dataset:
The output from human inspiratory motoneurone pools
Authors: Butler Jane E. , Gandevia Simon C.
Published: November 2007

Survival requires adequate pulmonary ventilation which, in turn, depends on adequate contraction of muscles acting on the chest wall in the presence of a patent upper airway. Bulbospinal outputs projecting directly and indirectly to ‘obligatory’ respiratory motoneurone pools generate the required muscle contractions. Recent studies of the phasic inspiratory output of populations of single motor units to five muscles acting on the chest wall (including the diaphragm) reveal that the time of onset, the progressive recruitment, and the amount of motoneuronal drive (expressed as firing frequency) differ among the muscles. Tonic firing with an inspiratory modulation of firing rate is common in low intercostal spaces of the parasternal and external intercostal muscles but rare in the diaphragm. A new time and frequency plot has been developed to depict the behaviour of the motoneurone populations. The magnitude of inspiratory firing of motor unit populations is linearly correlated to the mechanical advantage of the intercostal muscle region at which the motor unit activity is recorded. This represents a ‘neuromechanical’ principle by which the CNS controls motoneuronal output according to mechanical advantage, presumably in addition to the Henneman's size principle of motoneurone recruitment. Studies of the genioglossus, an obligatory upper airway muscle that helps maintain airway patency, reveal that it receives simultaneous inspiratory, expiratory and tonic drives even during quiet breathing. There is much to be learned about the neural drive to pools of human inspiratory and expiratory muscles, not only during respiratory tasks but also in automatic and volitional tasks, and in diseases that alter the required drive.
An Investigation Into the Hydrodynamic Efficiency of an Oscillating Water Column
Authors: Morris-Thomas Michael T. , Irvin Rohan J. , Thiagarajan Krish P.
Published: November 2007

An oscillating water column device enables the conversion of wave energy into electrical energy via wave interaction with a semi-submerged chamber coupled with a turbine for power take off. This present work concentrates on the wave interaction with the semi-submerged chamber, whereby a shore based oscillating water column (OWC) is studied experimentally to examine energy efficiencies for power take-off. The wave environment considered comprises plane progressive waves of steepnesses ranging from kA=0.01 to 0.22 and water depth ratios varying from kh=0.30 to 3.72, where k, A, and h denote the wave number, wave amplitude, and water depth, respectively. The key feature of this experimental campaign is a focus on the influence of front wall geometry on the OWC’s performance. More specifically, this focus includes: front wall draught, thickness, and aperture shape of the submerged front wall. We make use of a two-dimensional inviscid theory for an OWC for comparative purposes and to explain trends noted in the experimental measurements. The work undertaken here has revealed a broad banded efficiency centered about the natural frequency of the OWC. The magnitude and shape of the efficiency curves are influenced by the geometry of the front wall. Typical peak magnitude resonant efficiencies are in the order of 70%.
Measurements of Wave Induced Hull Girder Vibrations of an Ore Carrier in Different Trades
Authors: Storhaug Gaute , Moe Erlend , Holtsmark Gabriel
Published: November 2007

Currently, the conventional wave loading is the only effect considered in fatigue assessment of ships. Det Norske Veritas (DNV) has recently confirmed that fatigue damage from wave induced vibrations may be of similar magnitude as from the conventional wave loading (Moe et al., 2005, RINA, International Conference, Design and Operation of Bulk Carriers, London, Oct. 18–19, pp. 57–85). A 40% contribution to the total fatigue damage in deck amidships is documented through extensive measurements onboard an ore carrier (the reference ship) trading in the North Atlantic. The effect of strengthening the vessel, i.e., increasing the natural frequency by 10%, is ineffective in reducing the relative magnitude of the vibration damage. The wave induced vibration, often referred to as whipping and/or springing, also contributes to fatigue damage for other ship types and trades (Moe et al.). This paper considers the effect of trade. It indicates when the wave induced vibrations should be accounted for in the design phase with respect to fatigue damage. A second ore carrier (the target ship) is monitored with respect to the wave induced hull vibrations and their fatigue effect. Stress records from strain sensors located in the midship deck region are supplemented by wave radar and wind records. Based on the measurements, the vibration stress response and associated vibration induced fatigue damage are determined for varying wind and wave forces and relative headings. While the reference ship operates in the Canada to Europe ore trade, the target ship trades between Canada and Europe, Brazil and Europe, and South Africa and Europe. A procedure is suggested by Moe et al. to estimate the long term fatigue damage for different trades by utilizing the measured data from the reference ship. The vibration and wave damage are considered separately. By comparing the measured wave environment and the DNV North Atlantic scatter diagram, the effect of routing indicated a reduction of the fatigue damage by one-third. A slightly revised procedure is applied to estimate the effect of trade for the second ore carrier, comparing the long term predicted fatigue damage with the measured fatigue damage. The importance of trade is confirmed. However, the relative contribution of the vibration damage is shown to increase in less harsh environments. The target ship vibrates more than the reference ship for the same trade and Beaufort strength. The vibration damage of the target ship constitutes 56% of the total measured damage, and the high natural frequency is observed to have no significant effect.
Uncertainties in Extreme Wave Height Estimates for Hurricane-Dominated Regions
Authors: Jonathan Philip , Ewans Kevin
Published: November 2007

Inherent uncertainties in estimation of extreme wave heights in hurricane-dominated regions are explored using data from the GOMOS Gulf of Mexico hindcast for 1900–2005. In particular, the effect of combining correlated values from a neighborhood of 72 grid locations on extreme wave height estimation is quantified. We show that, based on small data samples, extreme wave heights are underestimated and site averaging usually improves estimates. We present a bootstrapping approach to evaluate uncertainty in extreme wave height estimates. We also argue in favor of modeling supplementary indicators for extreme wave characteristics, such as a high percentile (95%) of the distribution of 100-year significant wave height, in addition to its most probable value, especially for environments where the distribution of 100-year significant wave height is strongly skewed.
Effect of Strength Matching and Strain Hardening Capacity on Fracture
Performance of X80 Line Pipe Girth Welded Joint Subjected to Uniaxial Tensile
Loading
Authors: Motohashi Hiroyuki , Hagiwara Naoto
Published: November 2007

By conducting curved wide plate tensile tests for girth welded joints of X80 line pipe containing a surface notch in the weld metal, the effects of strength matching on fracture performance were evaluated. Parametric studies were also conducted using a finite element method simulating the experiments to clarify the effects of strain hardening capacity of the base metal, softening in the heat affected zone, and groove configuration on fracture performance. A strain at failure significantly decreased with the decreasing strength matching. This was expected to be due to a difference in local straining behavior at the notch tip caused by the shielding effect. The analytical studies revealed that the strain hardening capacity of the base metal, the softening in the heat affected zone, and the groove configuration affected the allowable strain for a given toughness level in the case of overmatching. However, these factors hardly affected the allowable strain in the case of undermatching.
Non-Gaussian Random Wave Simulation by Two-Dimensional Fourier Transform and Linear Oscillator Response to Morison Force
Authors: Zheng Xiang Yuan , Moan Torgeir , Quek Ser Tong
Published: November 2007

The one-dimensional fast Fourier transform (FFT) has been applied extensively to simulate Gaussian random wave elevations and water particle kinematics. The actual sea elevations/kinematics exhibit non-Gaussian characteristics that can be represented mathematically by a second-order random wave theory. The elevations/kinematics formulations contain frequency sum and difference terms that usually lead to expensive time-domain dynamic analyses of offshore structural responses. This study aims at a direct and efficient two-dimensional FFT algorithm for simulating the frequency sum terms. For the frequency-difference terms, inverse FFT and forward FFT are implemented, respectively, across the two dimensions of the wave interaction matrix. Given specified wave conditions, the statistics of simulated elevations/kinematics compare well with not only the empirical fits but also the analytical solutions based on a modified eigenvalue/eigenvector approach, while the computational effort of simulation is very economical. In addition, the stochastic analyses in both time domain and frequency domain show that, attributable to the second-order nonlinear wave effects, the near-surface Morison force and induced linear oscillator response are more non-Gaussian than those subjected to Gaussian random waves.
Scattering of Surface and Internal Waves by Rectangular
Dikes
Authors: Kumar P. Suresh , Bhattacharjee J. , Sahoo T.
Published: November 2007

The scattering of surface and internal waves by a single dike or a pair of identical dikes in a two-layer fluid is analyzed in two dimensions within the context of linearized theory of water waves. The dikes are approximated as cylinders of rectangular geometry and are placed in a two-layer fluid of finite depth. In the study, both the cases of surface-piercing and bottom-standing dikes are considered. The solution of the associated boundary value problem is derived by a matched eigenfunction expansion method. Because of the flow discontinuity at the interface, the eigenfunctions involved have an integrable singularity at the interface and the orthonormal relation used in the present analysis is a generalization of the classical one corresponding to a single-layer fluid. The reflection coefficients and force amplitudes are computed and analyzed in various cases. The computed results in a two-layer fluid are compared with those existing in the literature for a single-layer fluid. The results obtained by the matched eigenfunction expansion method are compared with that of wide-spacing approximation method, and it is observed that the results from both the methods are in good agreement when the dikes are widely spaced. The general behavior of reflection coefficients for interface-piercing and non-interface-piercing obstacles is found to be different in both cases of surface-piercing and bottom-standing dikes. Moreover, for surface-piercing dikes, the results show the possibility of very large resonant motions between the dikes but with a very narrow bandwidth for the frequency of interest.
Comment on "A Vestige of Earth's Oldest Ophiolite"
Authors: Nutman Allen P. , Friend Clark R. L.
Published: November 2007

Furnes
et al
. (Reports, 23 March 2007, p. 1704) reported the identification of an ophiolite sequence within the ∼3.8-billion-year-old Isua supracrustal belt. However, they did not acknowledge that the belt contains supracrustal rocks and mafic dikes of different ages, nor did they demonstrate that the proposed components of the ophiolite are coeval.
Response to Comments on "A Vestige of Earth's Oldest Ophiolite"
Authors: Furnes Harald , de Wit Maarten , Staudigel Hubert , Rosing Minik , Muehlenbachs Karlis
Published: November 2007

The comments by Nutman and Friend, and Hamilton, question our evidence for the presence of the Isua ophiolite. Their critical remarks are particularly directed at the veracity of our inferred sheeted-dike complex, the cogenicity of pillow lavas and dikes, and the nonexistence of modern equivalents. Here, we expand on our explanations in response to each of their comments to better justify our arguments and interpretation.
Comment on "A Vestige of Earth's Oldest Ophiolite"
Authors: Hamilton Warren B.
Published: November 2007

The claim by Furnes
et al
. (Reports, 23 March 2007, p. 1704) that Greenland metavolcanic rocks require Paleoarchean sea-floor spreading is incompatible with their own data. The purported sheeted dikes have the composition of pyroxenitic komatiite and could not have fed the adjacent ferroandesitic pillow lavas. Neither type has ophiolitic analogs, and both are likely ensialic.
A High-Resolution Root Spatiotemporal Map Reveals Dominant Expression Patterns
Authors: Brady Siobhan M. , Orlando David A. , Lee Ji-Young , Wang Jean Y. , Koch Jeremy , Dinneny José R. , Mace Daniel , Ohler Uwe , Benfey Philip N.
Published: November 2007

Transcriptional programs that regulate development are exquisitely controlled in space and time. Elucidating these programs that underlie development is essential to understanding the acquisition of cell and tissue identity. We present microarray expression profiles of a high-resolution set of developmental time points within a single
Arabidopsis
root and a comprehensive map of nearly all root cell types. These cell type–specific transcriptional signatures often predict previously unknown cellular functions. A computational pipeline identified dominant expression patterns that demonstrate transcriptional similarity between disparate cell types. Dominant expression patterns along the root's longitudinal axis do not strictly correlate with previously defined developmental zones, and in many cases, we observed expression fluctuation along this axis. Both robust co-regulation of gene expression and potential phasing of gene expression were identified between individual roots. Methods that combine these profiles demonstrate transcriptionally rich and complex programs that define
Arabidopsis
root development in both space and time.
TARP Auxiliary Subunits Switch AMPA Receptor Antagonists into Partial Agonists
Authors: Menuz Karen , Stroud Robert M. , Nicoll Roger A. , Hays Franklin A.
Published: November 2007

Quinoxalinedione compounds such as 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) are the most commonly used α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonists. However, we find that in the presence of transmembrane AMPA receptor regulatory proteins (TARPs), which are AMPA receptor auxiliary subunits, CNQX acts as a partial agonist. CNQX induced small depolarizing currents in neurons of the central nervous system, and reconstitution of this agonist activity required coexpression of TARPs. A crystal structure of CNQX bound to the TARP-less AMPA receptor ligand-binding domain showed that, although CNQX induces partial domain closure, this movement is not transduced into linker separation, suggesting that TARPs may increase agonist efficacy by strengthening the coupling between domain closure and channel opening. Our results demonstrate that the presence of an auxiliary subunit can determine whether a compound functions as an agonist or antagonist.
Engineering Modified Bt Toxins to Counter Insect Resistance
Authors: Soberón Mario , Pardo-López Liliana , López Idalia , Gómez Isabel , Tabashnik Bruce E. , Bravo Alejandra
Published: November 2007

The evolution of insect resistance threatens the effectiveness of
Bacillus thuringiensis
(Bt) toxins that are widely used in sprays and transgenic crops. Resistance to Bt toxins in some insects is linked with mutations that disrupt a toxin-binding cadherin protein. We show that susceptibility to the Bt toxin Cry1Ab was reduced by cadherin gene silencing with RNA interference in
Manduca sexta
, confirming cadherin's role in Bt toxicity. Native Cry1A toxins required cadherin to form oligomers, but modified Cry1A toxins lacking one α-helix did not. The modified toxins killed cadherin-silenced
M. sexta
and Bt-resistant
Pectinophora gossypiella
that had cadherin deletion mutations. Our findings suggest that cadherin promotes Bt toxicity by facilitating toxin oligomerization and demonstrate that the modified Bt toxins may be useful against pests resistant to standard Bt toxins.
The Piwi-piRNA Pathway Provides an Adaptive Defense in the Transposon Arms Race
Authors: Aravin Alexei A. , Hannon Gregory J. , Brennecke Julius
Published: November 2007

Increasingly complex networks of small RNAs act through RNA-interference (RNAi) pathways to regulate gene expression, to mediate antiviral responses, to organize chromosomal domains, and to restrain the spread of selfish genetic elements. Historically, RNAi has been defined as a response to double-stranded RNA. However, some small RNA species may not arise from double-stranded RNA precursors. Yet, like microRNAs and small interfering RNAs, such species guide Argonaute proteins to silencing targets through complementary base-pairing. Silencing can be achieved by corecruitment of accessory factors or through the activity of Argonaute itself, which often has endonucleolytic activity. As a specific and adaptive regulatory system, RNAi is used throughout eukarya, which indicates a long evolutionary history. A likely function of RNAi throughout that history is to protect the genome from both pathogenic and parasitic invaders.
A Gene Regulatory Network Subcircuit Drives a Dynamic Pattern of Gene Expression
Authors: Smith Joel , Theodoris Christina , Davidson Eric H.
Published: November 2007

Early specification of endomesodermal territories in the sea urchin embryo depends on a moving torus of regulatory gene expression. We show how this dynamic patterning function is encoded in a gene regulatory network (GRN) subcircuit that includes the
otx, wnt8
, and
blimp1
genes, the cis-regulatory control systems of which have all been experimentally defined. A cis-regulatory reconstruction experiment revealed that
blimp1
autorepression accounts for progressive extinction of expression in the center of the torus, whereas its outward expansion follows reception of the Wnt8 ligand by adjacent cells. GRN circuitry thus controls not only static spatial assignment in development but also dynamic regulatory patterning.
Molecular Basis for the Nerve Dependence of Limb Regeneration in an Adult Vertebrate
Authors: Kumar Anoop , Godwin James W. , Gates Phillip B. , Garza-Garcia A. Acely , Brockes Jeremy P.
Published: November 2007

The limb blastemal cells of an adult salamander regenerate the structures distal to the level of amputation, and the surface protein Prod 1 is a critical determinant of their proximodistal identity. The anterior gradient protein family member nAG is a secreted ligand for Prod 1 and a growth factor for cultured newt blastemal cells. nAG is sequentially expressed after amputation in the regenerating nerve and the wound epidermis—the key tissues of the stem cell niche—and its expression in both locations is abrogated by denervation. The local expression of nAG after electroporation is sufficient to rescue a denervated blastema and regenerate the distal structures. Our analysis brings together the positional identity of the blastema and the classical nerve dependence of limb regeneration.
4D Visualization of Transitional Structures in Phase Transformations by Electron Diffraction
Authors: Baum Peter , Yang Ding-Shyue , Zewail Ahmed H.
Published: November 2007

Complex systems in condensed phases involve a multidimensional energy landscape, and knowledge of transitional structures and separation of time scales for atomic movements is critical to understanding their dynamical behavior. Here, we report, using four-dimensional (4D) femtosecond electron diffraction, the visualization of transitional structures from the initial monoclinic to the final tetragonal phase in crystalline vanadium dioxide; the change was initiated by a near-infrared excitation. By revealing the spatiotemporal behavior from all observed Bragg diffractions in 3D, the femtosecond primary vanadium–vanadium bond dilation, the displacements of atoms in picoseconds, and the sound wave shear motion on hundreds of picoseconds were resolved, elucidating the nature of the structural pathways and the nonconcerted mechanism of the transformation.
Tales of a Small, But Crucial, Fish
Authors: Pauly Daniel
Published: November 2007

The Most Important Fish in the Sea
. Menhaden and America.
By H. Bruce Franklin
. Island Press, Washington, DC, 2007. 278 pp. $25. ISBN 9781597261241.

The author explores the roles of menhaden in the natural and national histories of the United States and the threats that current overexploitation poses to the fish's future.
Coherent Control of a Single Electron Spin with Electric Fields
Authors: Nowack K. C. , Koppens F. H. L. , Nazarov Yu. V. , Vandersypen L. M. K.
Published: November 2007

Manipulation of single spins is essential for spin-based quantum information processing. Electrical control instead of magnetic control is particularly appealing for this purpose, because electric fields are easy to generate locally on-chip. We experimentally realized coherent control of a single-electron spin in a quantum dot using an oscillating electric field generated by a local gate. The electric field induced coherent transitions (Rabi oscillations) between spin-up and spin-down with 90° rotations as fast as ∼55 nanoseconds. Our analysis indicated that the electrically induced spin transitions were mediated by the spin-orbit interaction. Taken together with the recently demonstrated coherent exchange of two neighboring spins, our results establish the feasibility of fully electrical manipulation of spin qubits.
Disentangling Genetic Variation for Resistance and Tolerance to Infectious Diseases in Animals
Authors: Råberg Lars , Sim Derek , Read Andrew F.
Published: November 2007

Hosts can in principle employ two different strategies to defend themselves against parasites: resistance and tolerance. Animals typically exhibit considerable genetic variation for resistance (the ability to limit parasite burden). However, little is known about whether animals can evolve tolerance (the ability to limit the damage caused by a given parasite burden). Using rodent malaria in laboratory mice as a model system and the statistical framework developed by plant-pathogen biologists, we demonstrated genetic variation for tolerance, as measured by the extent to which anemia and weight loss increased with increasing parasite burden. Moreover, resistance and tolerance were negatively genetically correlated. These results mean that animals, like plants, can evolve two conceptually different types of defense, a finding that has important implications for the understanding of the epidemiology and evolution of infectious diseases.
A Predictably Selective Aliphatic C–H Oxidation Reaction for Complex Molecule Synthesis
Authors: Chen Mark S. , White M. Christina
Published: November 2007

Realizing the extraordinary potential of unactivated sp
3
C–H bond oxidation in organic synthesis requires the discovery of catalysts that are both highly reactive and predictably selective. We report an iron (Fe)–based small molecule catalyst that uses hydrogen peroxide (H
2
O
2
) to oxidize a broad range of substrates. Predictable selectivity is achieved solely on the basis of the electronic and steric properties of the C–H bonds, without the need for directing groups. Additionally, carboxylate directing groups may be used to furnish five-membered ring lactone products. We demonstrate that these three modes of selectivity enable the predictable oxidation of complex natural products and their derivatives at specific C–H bonds with preparatively useful yields. This type of general and predictable reactivity stands to enable aliphatic C–H oxidation as a method for streamlining complex molecule synthesis.
Reminiscences of the Moon Trips
Authors: Pasachoff Jay M.
Published: November 2007

In the Shadow of the Moon
.
David Sington, Director
. THINKFilm, New York, in association with Discovery Films, 2007. 100 minutes.
www.intheshadowofthemoon.com

This documentary combines footage from NASA's archives with interviews of the surviving crew members of the nine Apollo spacecraft that journeyed to the Moon between 1968 and 1972.
Determination of Cytokine Protein Levels in Cervical Mucus Samples from Young Women by a Multiplex Immunoassay Method and Assessment of Correlates
Authors: Lieberman Jay A. , Moscicki Anna-Barbara , Sumerel Jan L. , Ma Yifei , Scott Mark E.
Published: November 2007

Cytokines in cervical mucus are likely to play important roles in controlling pathogens. The cervical mucosal environment is complex, however, with many endogenous and exogenous factors that may affect cytokine levels. We used a multiplex, suspension-array-based immunoassay method to measure 10 proinflammatory (interleukin-1β [IL-1β], IL-6, and IL-8) and immunoregulatory (gamma interferon [IFN-γ], IL-2, IL-4, IL-5, IL-10, IL-12, and IL-13) cytokines in cervical mucus specimens collected via ophthalmic sponge from 72 healthy, nonpregnant women and correlate their levels with biologic and behavioral covariates in a cross-sectional design. Proinflammatory and immunoregulatory cytokines were readily detected, although proinflammatory cytokines were present at markedly higher levels than were immunoregulatory cytokines. Among the covariates examined, the most striking finding was the significant (
P
≤ 0.05) association between depressed levels of the cytokines IFN-γ, IL-1β, IL-6, and IL-10 and cigarette smoking. Also, nonsignificant trends toward lower cytokine levels were found in the settings of incident and persistent human papillomavirus infection. The ready detection of proinflammatory cytokines may be reflective of the female genital tract as an anatomic site that is constantly exposed to immunogenic stimulation. Cigarette smoking appears to downregulate cytokine responses in the cervical mucosa, which may help explain the implicated role of tobacco use as a cofactor for cervical cancer development.
Human Skin Endothelial Cells Can Express All 10TLRGenes and Respond to Respective Ligands
Authors: Fitzner Nicole , Clauberg Sigrid , Essmann Frank , Liebmann Joerg , Kolb-Bachofen Victoria
Published: November 2007

Breakdown of the skin barrier requires the recognition of and rapid responses to invading pathogens. Since wounding usually also affects endothelial intactness, the expression of receptors of the Toll-like family involved in pathogen recognition in human skin vessel endothelia was examined. We found that human skin-derived microvascular endothelial cells can express all 10 Toll-like receptors (TLRs) currently known and will respond to respective ligands. Using immortalized skin-derived (HMEC-1) and primary dermal endothelial cells (HDMEC), we screened for TLR expression by real-time PCR. Endothelial cells express 7 (for HDMEC) and 8 (for HMEC-1) of the 10 known human TLRs under resting conditions but can express all 10 receptors in proinflammatory conditions. To provide evidence of TLR functionality, endothelial cells were challenged with TLR ligands, and after the TLR downstream signaling, MyD88 recruitment as well as early (interleukin-8 [IL-8] release) and late immune markers (inducible nitric oxide synthase mRNA expression) were monitored. Surprisingly, the responses observed were not uniform but were highly specific depending on the respective TLR ligand. For instance, lipopolysaccharides highly increased IL-8 release, but CpG DNA induced significant suppression. Additionally, TLR-specific responses were found to differ between resting and activated endothelial cells. These results show that human skin-derived endothelial cells can function as an important part of the innate immune response, can actively sense pathogen-associated molecular patterns, and can mount an increased or reduced inflammatory signal upon exposure to any of the currently known TLR ligands. Moreover, we also show here that proinflammatory conditions may affect TLR expression in a specific and nonuniform pattern.
Mannose-Binding Lectin Deficiency Facilitates AbdominalCandidaInfections in Patients with Secondary Peritonitis
Authors: van Till J. W. Olivier , Modderman Piet W. , de Boer Martin , Hart Margreet H. L. , Beld Marcel G. H. M. , Boermeester Marja A.
Published: November 2007

Mannose-binding lectin (MBL) deficiency due to variations in the MBL gene is associated with increased susceptibility to infections. In this study, the association between MBL deficiency and the occurrence of abdominal yeast infection (AYI) in peritonitis patients was examined. Eighty-eight patients with secondary peritonitis requiring emergency laparotomy were included. MBL genotype (wild type [WT] versus patients with variant genotypes), MBL plasma concentrations, andCandidarisk factors were examined in patients with and those without AYI (positive abdominal yeast cultures during [re]laparotomy). A variant MBL genotype was found in 53% of patients with AYI and 38% of those without AYI (P= 0.18). A significantly higher proportion of variant patients had an AYI during early peritonitis (during first laparotomy) than WT patients (39% versus 16%, respectively;P= 0.012). Patients with AYI had lower MBL levels than did patients without AYI (0.16 μg/ml [0.0 to 0.65 μg/ml] versus 0.65 μg/ml (0.19 to 1.95 μg/ml);P= 0.007). Intensity of colonization (odds ratio [OR], 1.1; 95% confidence interval [CI], 1.0 to 1.1), MBL plasma concentrations of <0.5 μg/ml (OR, 4.5; 95% CI, 1.2 to 16.3), and numbers of relaparotomies (OR, 1.7; 95% CI, 1.0 to 2.8) were independently associated with AYI. In summary, deficient MBL plasma levels were independently associated with the development of AYI in patients with secondary peritonitis and seemed to facilitate early infection.
Overlapping Population Structures of Nasal Isolates of
Staphylococcus aureus
from Healthy Dutch and American Individuals
Authors: Melles Damian C. , Tenover Fred C. , Kuehnert Matthew J. , Witsenboer Hanneke , Peeters Justine K. , Verbrugh Henri A. , van Belkum Alex
Published: November 2007

To understand
Staphylococcus aureus
nasal carriage and its relationship with subsequent disease, insight into the natural (nonclinical) bacterial population structure is essential. This study investigated whether the distributions of
S. aureus
genotypes that cause colonization differ by geographic locales. High-throughput amplified fragment length polymorphism (AFLP) analysis was performed on nasal isolates of
S. aureus
from healthy American (
n
= 391) and Dutch (
n
= 829) volunteers. In total, 164,970 binary outcomes, covering 135 different markers per isolate, were scored. Methicillin resistance was defined for all strains; pulsed-field gel electrophoresis typing was performed for the American isolates. The overall population structures of the American and Dutch
S. aureus
isolates were comparable. The same four major AFLP clusters (I to IV) and subclusters were identified for both collections. However, the Dutch methicillin-susceptible
S. aureus
(MSSA) isolates were overrepresented in AFLP cluster III (
P
= 0.0016). Furthermore, the majority of the American methicillin-resistant
S. aureus
isolates (90.5%) were located in AFLP cluster I (
P
< 0.0001). This result identifies differences in the local prevalence of certain
S. aureus
genotypes. AFLP clusters II and III, which represent multilocus sequence typing clonal complexes 30 and 45, respectively, account for 46.4% of all MSSA isolates in the study, suggesting that these two lineages have evolved as extremely successful pandemic colonizers of humans. In conclusion, the overall population structures of American and Dutch nasal carriage isolates of
S. aureus
are surprisingly similar, despite subtle geographic differences in the prevalence of certain
S. aureus
genotypes.
fimA
Genotypes and Multilocus Sequence Types of
Porphyromonas gingivalis
from Patients with Periodontitis
Authors: Enersen Morten , Olsen Ingar , Kvalheim Øyvind , Caugant Dominique A.
Published: November 2007

Fimbriae are important virulence factors of pathogenic bacteria, facilitating their attachment to host and bacterial cells. In the periodontal pathogen
Porphyromonas gingivalis
, the
fimA
gene is classified into six types (genotypes I, Ib, II, III, IV, and V) on the basis of different nucleotide sequences, with
fimA
genotypes II and IV being prevalent in isolates from patients with periodontitis. The aims of this study were to examine the distribution of
fimA
genotypes in a collection of 82
P. gingivalis
isolates from adult periodontitis patients of worldwide origin and to investigate the relationship between the
fimA
genotypes and the sequence types (STs), as determined by multilocus sequence typing (MLST), of the isolates. The
fimA
gene was amplified by PCR with primer sets specific for each genotype. The STs of all strains were assigned according to the MLST database for
P. gingivalis
(
www.pubmlst.org/pgingivalis
). The 82 strains showed extensive genetic diversity and were assigned to 69 STs. Only isolates with closely related STs harbored the same
fimA
genotype. Twenty-eight (34.1%) strains harbored
fimA
genotype II, while only the reference strain for
fimA
genotype V reacted with the primers specific for this genotype. Twenty-one isolates (25.6%) were positive by more than one of the
fimA
PCR assays; the most frequent combinations were genotypes I, Ib, and II (eight isolates) and genotypes I and II (four isolates). Sequencing of the
fimA
gene from selected isolates did not support the observed specific
fimA
genotype combinations, suggesting that the genotyping method used for the major fimbriae in
P. gingivalis
should be reevaluated.
Prospective Identification of Enteroviruses Involved in Meningitis in 2006 through Direct Genotyping in Cerebrospinal Fluid
Authors: Mirand Audrey , Henquell Cécile , Archimbaud Christine , Chambon Martine , Charbonne Françoise , Peigue-Lafeuille Hélène , Bailly Jean-Luc
Published: November 2007

Enterovirus infections were investigated with special emphasis on performing rapid molecular identification of enterovirus serotypes responsible for aseptic meningitis directly in cerebrospinal fluid (CSF). Enterovirus genotyping was carried out directly with specimens tested for the diagnostic procedure, using two seminested PCR assays designed to amplify the complete and partial gene sequences encoding the VP1 and VP4/VP2 capsid proteins, respectively. The method was used for identifying the enterovirus serotypes involved in meningitis in 45 patients admitted in 2005. Enterovirus genotyping was achieved in 98% of the patients studied, and we obtained evidence of 10 of the most frequent serotypes identified earlier by genotyping of virus isolates. The method was applied for the prospective investigation of 54 patients with meningitis admitted consecutively in 2006. The enterovirus serotypes involved were identified with the cerebrospinal fluid (CSF) of 52 patients (96%) and comprised 13 serotypes within the human enterovirus B species and 1 within the human enterovirus A species. The three most common serotypes were echovirus 13 (E13; 24%), E6 (23%), and coxsackievirus B5 (11.5%), a pattern different from that observed in 2005. Genotyping of virus isolates was also performed in 35 patients in 2006 (meningitis,
n
= 31; other diseases,
n
= 4). By comparison, direct genotyping in CSF yielded a more complete pattern of enterovirus serotypes, thereby allowing the detection of rare serotypes: three less common serotypes (CB2, E21, and E27) were not detected by indirect genotyping alone. The study shows the feasibility of prospective enterovirus genotyping within 1 week in a laboratory setting.
Comparison of the Human Immunodeficiency Virus (HIV) Type 1-Specific Immunoglobulin G Capture Enzyme-Linked Immunosorbent Assay and the Avidity Index Method for Identification of Recent HIV Infections
Authors: Loschen Stephan , Bätzing-Feigenbaum Jörg , Poggensee Gabriele , Cordes Christiane , Hintsche Bettina , Rausch Michael , Dupke Stephan , Gohlke-Micknis Silvia , Rödig Jana , Hamouda Osamah , Kücherer Claudia
Published: November 2007

The sensitivity and specificity of the human immunodeficiency virus (HIV) type 1-specific immunoglobulin G capture enzyme-linked immunosorbent assay (BED-CEIA) were compared with those of the avidity index method to identify recent HIV infection using a panel of 148 samples (81 patients) representing durations of infection ranging from 0 to 222 weeks. The results from the two tests were similar (sensitivity of 80% versus 74% [
P
= 0.53]; specificity of 86% versus 82% [
P
= 0.67]).
Evidence from Multiplex Molecular Assays for Complex Multipathogen Interactions in Acute Respiratory Infections
Authors: Brunstein John D. , Cline Christy L. , McKinney Steven , Thomas Eva
Published: November 2007

While most diagnostic processes cease with the detection of the first relevant infectious agent, newer multiplexed molecular methods which provide simultaneous analysis of multiple agents may give a more accurate representation of the true pathogen spectrum in these samples. To examine this in the context of respiratory infections, acute-phase respiratory specimens submitted to our clinical diagnostic microbiology/virology laboratory for our routine VIRAP diagnosis protocol during the spring 2006 peak respiratory infection season were processed in parallel by analysis with Genaco (QiaPlex) ResPlex I and ResPlex II molecular diagnostic panels. A total of 1,742 specimens were examined for 21 relevant targets each. The resulting data reveal that multiple infections are frequent and provide evidence for complex interactions between different infectious agents. Statistically relevant association patterns (both positive and negative) were observed between particular pathogens. While some interactions we observed are substantiated by prior reports in the literature, several specific patterns do not appear to have been reported previously. In addition, we report preliminary clinical evidence which supports a hypothesis that these coinfections are medically relevant and that effective treatment for severe respiratory tract infections will increasingly require diagnosis of all involved pathogens, as opposed to single-pathogen reporting.
Evaluation of a Commercialized In Situ Hybridization Assay for Detecting Human Papillomavirus DNA in Tissue Specimens from Patients with Cervical Intraepithelial Neoplasia and Cervical Carcinoma
Authors: Guo Ming , Gong Yun , Deavers Michael , Silva Elvio G. , Jan Yee Jee , Cogdell David E. , Luthra Rajyalashmi , Lin E. , Lai Hung Cheng , Zhang Wei , Sneige Nour
Published: November 2007

To evaluate a commercialized in situ hybridization (ISH) assay for detecting human papillomavirus (HPV) DNA, we compared the ability of a new ISH probe, Inform HPV III (Ventana Medical Systems, Tucson, AZ), to that of PCR assays to detect HPV DNA in cervical tissue specimens with normal cervix (20 cases), cervical intraepithelial neoplasia (CIN; CIN 1, 27 cases; CIN 2, 28 cases; and CIN 3, 33 cases), and cervical carcinoma (29 cases). General HPV DNA was detected using consensus primer-mediated PCR assays. HPV genotyping was performed by using EasyChip HPV blot (King Car Yuan Shan Institute, I-Lan, Taiwan). HPV16 integration status (E2/E6 ratio) was determined by using quantitative real-time PCR. Our findings showed that the ISH and PCR had fair to good agreements in detecting HPV DNA across all CIN categories without significant differences (Kappa coefficient, 0.34 to 0.63;
P
= 0.13 to 1.0). However, ISH detected significantly fewer HPV-positive cases in carcinoma than PCR did (Kappa coefficient, 0.2;
P
= 0.03). Eleven cases with ISH
−
PCR
+
results had HPV types that can be detected by Inform HPV III. Five carcinoma cases with ISH
−
PCR
+
results showed a significantly higher level of integrated HPV16 (
P
= 0.008) than did the ISH
+
cases. As a consequence, lower copy numbers of episomal HPV16 in carcinoma might be the cause for the false-negative ISH results. Although the punctate signal pattern of HPV significantly increased with the severity of disease (
P
trend = 0.01), no significant difference in the HPV16 integration status was observed between the cases with a punctate signal only and the cases with mixed punctate and diffuse signals (
P
= 0.4). In conclusion, ISH using the Inform HPV III probe seems comparable to PCR for detecting HPV DNA in cervical tissue with CINs. False-negative ISH results appear to be associated with the lower copy numbers of the episomal HPV16 but not with the ability of the Inform HPV III probe to detect specific HPV types. In addition, signal patterns, especially a mixed punctate and diffuse pattern of HPV, cannot be reliably used to predict viral integration status.
Rapid Diagnosis of Human Brucellosis by Quantitative Real-Time PCR: a Case Report of Brucellar Spondylitis
Authors: Navarro-Martínez Amalia , Navarro Elena , Castaño Maria Jesús , Solera Javier
Published: November 2007

Blood samples and a bone biopsy specimen from one patient diagnosed with spondylodiscitis of unknown etiology were analyzed by quantitative real-time PCR to detectBrucella melitensis. The high sensitivity and specificity of this assay allowed the diagnosis of brucellar spondylitis within 24 h, a result that we were unable to obtain through the use of conventional methods.
Specimen Dilution Improves Sensitivity of the Amplified
Mycobacterium tuberculosis
Direct Test for Smear Microscopy-Positive Respiratory Specimens
Authors: Guerra Renata L. , Baker James F. , Alborz Roya , Armstrong Derek T. , Kiehlbauch Julia A. , Conde Marcus B. , Dorman Susan E. , Hooper Nancy M.
Published: November 2007

Specimen dilution has been proposed as a strategy to minimize amplified
Mycobacterium tuberculosis
direct (MTD) test inhibition (N. Pollock, J. Westerling, and A. Sloutsky, Am. J. Clin. Pathol. 126:142-147, 2006; A. Sloutsky, L. L. Han, and B. G. Werner, J. Clin. Microbiol. 42:1547-1551, 2004). We evaluated the impact of respiratory specimen dilution on MTD test accuracy in a public health laboratory. The difference in MTD test sensitivity between the dilution and conventional methods was 15.9% (
P
= 0.001) for smear microscopy-positive specimens and −3.6% (
P
= 0.38) for smear microscopy-negative specimens.
Multicenter Evaluation of the
Candida albicans
/
Candida glabrata
Peptide Nucleic Acid Fluorescent In Situ Hybridization Method for Simultaneous Dual-Color Identification of
C. albicans
and
C. glabrata
Directly from Blood Culture Bottles
Authors: Shepard Janeen R. , Addison Rachel M. , Alexander Barbara D. , Della-Latta Phyllis , Gherna Michael , Haase Gerhard , Hall Gerri , Johnson Jennifer K. , Merz William G. , Peltroche-Llacsahuanga Heidrun , Stender Henrik , Venezia Richard A. , Wilson Deborah , Procop Gary W. , Wu Fann , Fiandaca Mark J.
Published: November 2007

We evaluated the performance of the
Candida albicans
/
Candida glabrata
peptide nucleic acid fluorescent in situ hybridization (PNA FISH) method, a rapid two-color assay for detection of
C. albicans
and
C. glabrata
, in a multicenter study. The assay is designed for use directly from positive blood culture bottles in a FISH format. Intact, fixed cells are labeled fluorescent green (
C. albicans
) or fluorescent red (
C. glabrata
) by rRNA hybridization of fluorophore-labeled PNA probes. Results are available <3 h after cultures signal positive. An evaluation of 197 routine blood culture bottles newly positive for yeast by Gram staining was performed at five hospitals. The sensitivities of detection for
C. albicans
, and
C. glabrata
were 98.7% (78/79) and 100% (37/37), respectively, and the specificity for both components of the assay was 100% (82/82). The assay was also evaluated with 70 fungal reference strains and was challenged in the BacT/ALERT microbiological detection system with spiked blood culture bottles. These results support the use of the assay for rapid, simultaneous identification of
C. albicans
and
C. glabrata
in positive blood culture bottles. This rapid assay may aid in the selection of initial antifungal drugs, leading to improved patient outcomes.
Emergence of Fluoroquinolone-Resistant
Haemophilus influenzae
Strains among Elderly Patients but Not among Children
Authors: Yokota Shin-ichi , Ohkoshi Yasuo , Sato Kiyoshi , Fujii Nobuhiro
Published: November 2007

We screened 457
Haemophilus influenzae
strains isolated in Japan during 2002 to 2004 and identified 12 fluoroquinolone-resistant strains (2.6%). The resistant strains were divided into three genotypes (eight, three, and one of each type). These were isolated from patients over 58 years of age. Several fluoroquinolone-resistant clones appeared to have invaded the population of elderly patients in a particular area, Sapporo city.
High Rate of Human Bocavirus and Adenovirus Coinfection in Hospitalized Israeli Children
Authors: Hindiyeh Musa Y. , Keller Nathan , Mandelboim Michal , Ram Daniela , Rubinov Jana , Regev Liora , Levy Virginia , Orzitzer Sara , Shaharabani Hilda , Azar Roberto , Mendelson Ella , Grossman Zehava
Published: November 2007

We investigated coinfection of human bocavirus (HBoV) and other respiratory viruses in hospitalized children by real-time PCR. A high rate (69.2%) of adenovirus infection was found among children infected with HBoV. Such high rates of HboV-adenovirus coinfection have not been previously reported, underscoring the need to investigate the contribution of HBoV in patient clinical presentations.
Human Immunodeficiency Virus Type 1 Vif Functionally Interacts with Diverse APOBEC3 Cytidine Deaminases and Moves with Them between Cytoplasmic Sites of mRNA Metabolism
Authors: Marin Mariana , Golem Sheetal , Rose Kristine M. , Kozak Susan L. , Kabat David
Published: November 2007

Vif
IIIB
, which has been a standard model for the viral infectivity factor of human immunodeficiency virus type 1 (HIV-1), binds the cytidine deaminase APOBEC3G (A3G) and induces its degradation, thereby precluding its lethal incorporation into assembling virions. Additionally, Vif
IIIB
less efficiently degrades A3F, another potent anti-HIV-1 cytidine deaminase. Although the APOBEC3 paralogs A3A, A3B, and A3C have weaker anti-HIV-1 activities and are only partially degraded by Vif
IIIB
, we found that Vif
IIIB
induces their emigration from the nucleus to the cytosol and thereby causes net increases in the cytosolic concentrations and anti-HIV-1 activities of A3A and A3B. In contrast, some other Vifs, exemplified by Vif
HXB2
and Vif
ELI-1
, much more efficiently degrade and thereby neutralize all APOBEC3s. Studies focused mainly on A3F imply that it occurs associated with mRNA-PABP1 in translationally active polysomes and to a lesser extent in mRNA processing bodies (P-bodies). A3F appears to stabilize the P-bodies with which it is associated. A correspondingly small proportion of Vif
IIIB
also localizes in P-bodies in an A3F-dependent manner. Stress causes A3A, A3B, A3C, and A3F to colocalize efficiently with Vif
IIIB
and mRNA-PABP1 complexes in stress granules in a manner that is prevented by cycloheximide, an inhibitor of translational elongation. Coimmunoprecipitation studies suggest that Vifs from different HIV-1 isolates associate with all tested APOBEC3s. Thus, Vifs interact closely with structurally diverse APOBEC3s, with effects on their subcellular localization, degradation rates, and antiviral activities. Cytosolic APOBEC3-Vif complexes are predominantly bound to mRNAs that dynamically move between translationally active and storage or processing pools.