bluuebunny/crossref_metadata_2025 huggingface dataset:
An assessment of the impact of floodplain woodland on flood flows
Authors: Thomas H. , Nisbet T. R.
Published: October 2006

This paper examines the potential role of floodplain woodland in flood alleviation. In theory, the presence of trees and associated woody debris on the floodplain increases the hydraulic roughness, thus slowing down flood flows and enhancing flood storage. One and two‐dimensional models were used to simulate a 2.2 km reach of river in south‐west England to test this theory for a 1 in 100 year flood using appropriate roughness parameters. Both models predicted a reduction in water velocity within the woodland, increasing water level by up to 270 mm and creating a backwater effect that extended nearly 400 m upstream. Flood storage increased by 15 and 71%, while flood peak travel time was increased by 30 and 140 min for the two scenarios simulated. The results suggest that there is considerable scope for using strategically placed floodplain woodland to alleviate downstream flooding. In particular, it offers a means of tackling the increased flood risk associated with climate change.
Learning from the extreme River Tyne flood in January 2005
Authors: Archer David R. , Leesch Francois , Harwood Kirsty
Published: October 2006

Extreme floods often demonstrate unanticipated characteristics that pose problems for management and response. The floods on the Tyne and Eden in January 2005 provided numerous examples of such unexpected response. This paper describes characteristics of storm rainfall and runoff generation on the River Tyne catchment, flood effects and damage. Unusual aspects of hydrological behaviour are highlighted as a basis for assessing what lessons can be learned for flood risk management. These include problems associated with coincidence of extreme wind speeds and rainfall, the retarding influence of floodplain storage on flood wave travel time in extreme flows, the influence of critical storm duration on the severity of the resulting flood on headwaters and main river, and the variety of mechanisms of flood occurrence. The occurrence of such an extreme flood provides the opportunity to validate and enhance the review process of the Environment Agency's flood zone maps.
Human skeletal muscle fibre type variations correlate with PPARα, PPARδ and PGC‐1α mRNA
Authors: Krämer D. K. , Ahlsén M. , Norrbom J. , Jansson E. , Hjeltnes N. , Gustafsson T. , Krook A.
Published: October 2006

Aims:  Studies from genetically modified animals have been instrumental in highlighting genes and their products involved in the regulation of muscle fibre type and oxidative phenotypes; however, evidence in humans is limited. Our aim was therefore to investigate expression of those genes implicated in the regulation of oxidative fibre phenotypes in humans.

Methods:  Using quantitative polymerase chain reaction we determined mRNA expression of selected genes in skeletal muscle from three different groups, displaying physiological and pathological variations in muscle fibre type, activity and skeletal muscle metabolism respectively: (i) elite athletes (cyclists), with an increased proportion of type I slow twitch, oxidative fibres, (ii) normally active subjects with an average fibre type distribution, and (iii) spinal cord‐injured subjects with a low proportion of type I fibres.

Results:  Skeletal muscle mRNA expression of calcineurin Aα and Aβ, peroxisome proliferator‐activated receptor (PPAR)‐α and ‐δ, and PPAR gamma coactivator (PGC)‐1α and ‐1β was determined. Calcineurin Aα and calcineurin Aβ mRNA expression was similar between groups. In contrast, mRNA expression of PPARα, PPARδ, PGC‐1α and ‐1β was increased in athletes, when compared with normally active subjects. Furthermore, mRNA expression of PPARα, PPARδ, PGC‐1α and ‐1β was reduced in spinal cord‐injured subjects. Additionally, PPARα, PPARδ and PGC‐1α correlated with oxidative fibre content.

Conclusion:  Skeletal muscle mRNA expression of PPARα, PPARδ, PGC‐1α and ‐1β reflects differences in type I muscle fibres associated with pathologically and physiologically induced skeletal muscle fibre type differences.
A slowly inactivating sodium current (INa2) in the plateau range in canine cardiac Purkinje single cells
Authors: Vassalle Mario , Bocchi Leonardo , Du Fuyong
Published: October 2006

The action potential of Purkinje fibres is markedly shortened by tetrodotoxin, suggesting the possibility that a slowly inactivating sodium current might flow during the plateau. The aim of the present experiments was to investigate, in canine cardiac Purkinje single cells by means of a whole cell patch clamp technique, whether a sodium current slowly inactivates at less negative potentials and (if so) some of its distinctive characteristics. The results showed that a 500 ms depolarizing step from a holding potential of −90 mV to −50 mV induced the fast inward current INa (labelled here INa1). With steps to −40 mV or less negative values, a slowly decaying component (tentatively labelled here INa2) appeared, which peaked at −30 to −20 mV and decayed slowly and incompletely during the 500 ms steps. The INa2 was present also during steps to −10 mV, but then the transient outward current (Ito) appeared. When the holding potential (Vh) was decreased to −60 to −50 mV, INa2 disappeared even if a small INa1 might still be present. Tetrodotoxin (30 μm), lignocaine (100 μm) and cadmium (0.2 mm; but not manganese, 1 mm) blocked INa2. During fast depolarizing ramps, the rapid inactivation of INa1 was followed by a negative slope region. During repolarizing ramps, a region of positive slope was present, whereas INa1 was absent. At less negative values of Vh, the amplitude of the negative and positive slopes became gradually smaller. Gradually faster ramps increased the magnitude of the negative slope, and tetrodotoxin (30 μm) reduced or abolished it. Thus, Purkinje cells have a slowly decaying inward current owing to Na+ entry (INa2) that is different in several ways from the fast INa1 and that appears important for the duration of the plateau.
Postsynaptic origin of CB1‐dependent tonic inhibition of GABA release at cholecystokinin‐positive basket cell to pyramidal cell synapses in the CA1 region of the rat hippocampus
Authors: Neu Axel , Földy Csaba , Soltesz Ivan
Published: October 2006

Cholecystokinin‐positive (CCK+) basket cells are a major source of perisomatic GABAergic inputs to CA1 pyramidal cells. These interneurons express high levels of presynaptic cannabinoid type 1 (CB1) receptors that mediate short‐term depression of GABA release following depolarization of postsynaptic cells. However, it is not known whether GABA release from CA1 CCK+ basket cells is under tonic endocannabinoid inhibition. In paired patch‐clamp recordings, action potentials in presynaptic CCK+ basket cells evoked large IPSCs with fast kinetics in pyramidal cells. The proportion of action potentials that failed to evoke GABA release varied markedly between pairs, from highly reliable to virtually silent connections. Application of the CB1 receptor antagonist AM251 (10 μm) decreased the proportion of failures, revealing a persistent suppression of synaptic transmission by CB1 receptors. However, AM251 had no significant effect on the failure rate when the calcium chelator BAPTA (10 mm) was introduced into the postsynaptic cell, indicating that the tonic inhibition of GABA release by CB1 receptors is homosynaptically controlled by the postsynaptic cell, and that it is not due to constitutive CB1 receptor activity. Application of muscarinic or metabotropic glutamate receptor agonists inhibited synaptic transmission exclusively through the release of endocannabinoids from postsynaptic cells in a manner that could not be blocked by postsynaptic BAPTA, and had no direct effect on transmission. In contrast, GABAB receptor activation directly blocked GABA release, but there was no evidence for tonic inhibition of GABA release by GABAB receptors. Neither serotonergic nor μ‐opioid agonists had significant influence on GABA release from CCK+ axon terminals. These results reveal that GABA release from CA1 CCK+ basket cells is under homosynaptic tonic inhibition by endocannabinoids, and it is subject to both direct and indirect modulation by various G‐protein‐dependent neuromodulators.
Physiological properties of spinal lamina II GABAergic neurons in mice following peripheral nerve injury
Authors: Schoffnegger Doris , Heinke Bernhard , Sommer Claudia , Sandkühler Jürgen
Published: October 2006

Aberrant GABAergic inhibition in spinal dorsal horn may underlie some forms of neuropathic pain. Potential, but yet unexplored, mechanisms include reduced excitability, abnormal discharge patterns or altered synaptic input of spinal GABAergic neurons. To test these hypotheses, we quantitatively compared active and passive membrane properties, firing patterns in response to depolarizing current steps and synaptic input of GABAergic neurons in spinal dorsal horn lamina II of neuropathic and of control animals. Transgenic mice were used which expressed enhanced green fluorescent protein (EGFP) controlled by the GAD67 promoter, thereby labelling one‐third of all spinal GABAergic neurons. In all neuropathic mice included in this study, chronic constriction injury of one sciatic nerve led to tactile allodynia and thermal hyperalgesia. Control mice were sham‐operated. Membrane excitability of GABAergic neurons from neuropathic or sham‐treated animals was indistinguishable. The most frequent firing patterns observed in neuropathic and sham‐operated animals were the initial burst (neuropathic: 46%, sham‐treated: 42%), the gap (neuropathic: 31%, sham‐treated: 29%) and the tonic firing pattern (neuropathic: 16%, sham‐treated: 24%). The synaptic input from dorsal root afferents was similar in neuropathic and in control animals. Thus, a reduced membrane excitability, altered firing patterns or changes in synaptic input of this group of GABAergic neurons in lamina II of the spinal cord dorsal horn are unlikely causes for neuropathic pain.
Implementation Issues in 3D Wind Flow Predictions Over Complex Terrain
Authors: Prospathopoulos John , Voutsinas Spyros G.
Published: October 2006

Practical aspects concerning the use of 3D Navier-Stokes solvers as prediction tools for micro-siting of wind energy installations are considered. Micro-siting is an important issue for a successful application of wind energy in sites of complex terrain. There is a constantly increasing interest in using mean wind flow predictions based on Reynolds averaged Navier-Stokes (RANS) solvers in order to minimize the number of required field measurements. In this connection, certain numerical aspects, such as the extent of the numerical flow domain, the choice of the appropriate inflow boundary conditions, and the grid resolution, can decisively affect the quality of the predictions. In the present paper, these aspects are analyzed with reference to the Askervein hill data base of full scale measurements. The objective of the work is to provide guidelines with respect to the definition of appropriate boundary conditions and the construction of an adequate and effective computational grid when a RANS solver is implemented. In particular, it is concluded that (a) the ground roughness affects the predictions significantly, (b) the computational domain should have an extent permitting the full development of the flow before entering the region of interest, and (c) the quality of the predictions at the local altitude maxima depends on the grid density in the main flow direction.
Influence of Atmospheric Stability on Wind Turbine Power Performance Curves
Authors: Sumner Jonathon , Masson Christian
Published: October 2006

The impact of atmospheric stability on vertical wind profiles is reviewed and the implications for power performance testing and site evaluation are investigated. Velocity, temperature, and turbulence intensity profiles are generated using the model presented by Sumner and Masson. This technique couples Monin-Obukhov similarity theory with an algebraic turbulence equation derived from the k-ϵ turbulence model to resolve atmospheric parameters u*, L, T*, and z0. The resulting system of nonlinear equations is solved with a Newton-Raphson algorithm. The disk-averaged wind speed u¯disk is then evaluated by numerically integrating the resulting velocity profile over the swept area of the rotor. Power performance and annual energy production (AEP) calculations for a Vestas Windane-34 turbine from a wind farm in Delabole, England, are carried out using both disk-averaged and hub height wind speeds. Although the power curves generated with each wind speed definition show only slight differences, there is an appreciable impact on the measured maximum turbine efficiency. Furthermore, when the Weibull parameters for the site are recalculated using u¯disk, the AEP prediction using the modified parameters falls by nearly 5% compared to current methods. The IEC assumption that the hub height wind speed can be considered representative tends to underestimate maximum turbine efficiency. When this assumption is further applied to energy predictions, it appears that the tendency is to overestimate the site potential.
3D Woven Carbon/Glass Hybrid Spar Cap for Wind Turbine Rotor Blade
Authors: Mohamed Mansour H. , Wetzel Kyle K.
Published: October 2006

This paper presents the design and analysis for a spar cap for a wind turbine rotor blade. The cap is formed of an integral, unitary 3D woven material (3WEAVE®) having constant thickness; spar cap weight is varied and controlled by appropriately tapering the cap width from the blade root to tip. This analysis is employed for 24-m and 37-m rotor blades. These studies are conducted parametrically, examining a range of 3WEAVE® materials incorporating varying fractions of glass and carbon fibers, and hence exhibiting a range of structural properties and material costs. These parametric studies are used to determine the impact on blade weight and cost resulting from the various materials studied. Detailed results are presented in the form of tables to enable candidate materials to be evaluated as they are developed.
Stall in Yawed Flow Conditions: A Correlation of Blade Element Momentum Predictions With Experiments
Authors: Haans Wouter , Sant Tonio , van Kuik Gijs , van Bussel Gerard
Published: October 2006

Yawed flow conditions introduce unsteady loads in a wind turbine that affect generated power quality and fatigue life. An unsteady phenomenon of special concern is dynamic stall, due to the significant load fluctuations associated with it. Although the assumptions underlying blade element momentum (BEM) models are totally inadequate in yawed flow conditions, these models, modified with engineering models, are still widely used in industry. It is therefore relevant to assess the capabilities of BEM models in predicting the location of dynamic stall on the blade for a rotor in yawed flow conditions. A rotor model is placed in an open jet wind tunnel and tested in yawed flow conditions. The locations of dynamic stall on the blade of a rotor model as a function of the blade position are observed. Two experimental techniques are used; tufts glued to the blade and hot-film anemometry in the near wake. The results from the two techniques are compared and possible causes for differences are identified. Furthermore, the rotor model in yaw is modeled with a simple BEM model, utilizing a Gormont dynamic stall model. The regions of dynamic stall on the blades predicted by the BEM model are compared with the experimental results. The BEM model seems capable of a crude prediction of the dynamic stall locations found for the rotor model in yawed flow conditions.
Extension of a Helicoidal Vortex Model to Account for Blade Flexibility and Tower Interference
Authors: Chattot Jean-Jacques
Published: October 2006

The unsteady vortex method has been extended to account for blade flexibility and tower interference. These are two potential sources of unsteadiness of the flow past a wind turbine blade. The cases presented correspond to an incoming flow speed V=5m∕s and low yaw angles and V=8, 10, and 12m∕s and zero yaw. Comparisons of the root flap bending moments predicted by the model with the National Renewable Energy Laboratory (NREL) experimental data indicate that the NREL blades designed for the wind tunnel campaigns are quite rigid and that the tower interference is responsible for unsteadiness that is well captured by the model for zero yaw as well as for yaw of 5, 10 and 20deg.
Effect of Blade Torsion on Modeling Results for the Small Wind Research Turbine (SWRT)
Authors: Corbus Dave , Hansen A. Craig , Minnema Jeff
Published: October 2006

The small wind research turbine (SWRT) testing project was initiated with the goal of better characterizing both small wind turbine loads and dynamic behavior. The main purpose of the testing was to produce high quality data sets for model development and validation and to help the wind industry further their understanding of small wind turbine behavior, including furling. Previous papers have discussed modeling results for the SWRT using the FAST aeroelastic simulator. This paper summarizes modeling results from both the FAST and ADAMS aeroelastic simulators. The ADAMS model allows for blade torsional stiffness to be modeled, which is shown to significantly improve the agreement between model and test results for rotor speed and explain variances in previous comparisons between the SWRT FAST modeling results and the SWRT test data. The ADAMS model results also show that the aerodynamic pitching moment impacts the blade torsion more than the inertial forces.
Computational Analysis of a Inverted Double-Element Airfoil in Ground Effect
Authors: Mahon Stephen , Zhang Xin
Published: October 2006

The flow around an inverted double-element airfoil in ground effect was studied numerically, by solving the Reynolds averaged Navier-Stokes equations. The predictive capabilities of six turbulence models with regards to the surface pressures, wake flow field, and sectional forces were quantified. The realizable k−ε model was found to offer improved predictions of the surface pressures and wake flow field. A number of ride heights were investigated, covering various force regions. The surface pressures, sectional forces, and wake flow field were all modeled accurately and offered improvements over previous numerical investigations. The sectional forces indicated that the main element generated the majority of the downforce, whereas the flap generated the majority of the drag. The near field and far field wake development was investigated and suggestions concerning reduction of the wake thickness were offered. The main element wake was found to greatly contribute to the overall wake thickness with the contribution increasing as the ride height decreased.
Ejection Process Simulation for a Piezoelectric Microdroplet Generator
Authors: Yang An-Shik , Tsai Wei-Ming
Published: October 2006

The purpose of this work is to investigate the liquid ejection process of a novel microdroplet generator applying a computational approach. In simulations, the theoretical model is based on the unsteady three-dimensional conservation equations of mass and momentum with the treatment of surface tension effect at the gas-liquid boundary by the continuous surface force scheme. The volume-of-fluid method along with the piecewise linear interface construction technique is implemented to describe the interfacial movements. The time evolution of droplet meniscus shape is predicted and compared to Shield’s microphotographed images for the computer code validation. To explore the practicability of the proposed new microdroplet generator, the flow behavior during the stages of liquid ejection and droplet formation are examined with water as the baseline test fluid for a full ejection cycle of 50μs. In addition, 12 numerical experiments were conducted to determine droplet ejection characteristics by systematically varying the ejection time period as well as surface tension and viscosity of liquids. Simulations reveal that a liquid strand with a shorter breakup time and a longer breakup length could be achieved by reducing the ejection time and decreasing the liquid surface tension and viscosity. For the ejection time greater than 4.0μs, the ejection velocity is too low to render a sufficient momentum for droplet breakup. The feasibility studies have demonstrated the potential of this proposed microdroplet generator in dispensing diverse liquids with the surface tension and the viscosity up to 0.08N∕m and 3.0cps.
Influence of Flow Coefficient, Stagger Angle, and Tip Clearance on Tip Vortex in Axial Compressors
Authors: Yoon Yong Sang , Song Seung Jin , Shin Hyoun-Woo
Published: October 2006

Experiments have been performed on the low speed research compressor (LSRC) at General Electric Aircraft Engines to investigate the effects of flow coefficient, stagger angle, and tip clearance on tip vortex. Time resolved casing pressure distributions over the third stage rotor have been acquired with high-frequency-response pressure transducers. Also, tip vortex strength and trajectory have been estimated from the casing pressure fluctuations which have been obtained simultaneously from various axial locations. As flow coefficient decreases, tip vortex gets strengthened and migrates upstream. The stagger angle increase weakens the tip vortex and moves it downstream slightly because the blade loading is decreased. However, tip leakage vortex is influenced mainly by tip clearance, and there exists a “critical” tip clearance which determines the type of tip vortex trajectory (“straight” or “kinked”). As predicted by others, tip vortex gets strengthened with increasing tip clearance. However, unlike the predictions, the tip vortex trajectory moves upstream with increasing tip clearance. Furthermore, with tip clearance above a “critical” value, the tip vortex trajectory is no longer straight but shows a kink in the passage.
DSMC Simulation of Subsonic Flows in Parallel and Series Microchannels
Authors: Le M. , Hassan I. , Esmail N.
Published: October 2006

Flows in uniform, parallel, and series microchannels have been investigated using the direct simulation Monte Carlo (DSMC) method. For the uniform microchannel cases, at higher pressure ratio, mixed Kn-regime flows were observed, where the Knudsen number (Kn) varies from below 0.1 to above 0.1. Also, the higher pressure ratio makes the flow accelerate more as the flow develops through the uniform microchannel. In order to examine the heat transfer characteristics between the wall and the bulk flow, a linear temperature distribution was imposed on the wall. Most of the wall heat flux occurs within the channel entrance region while it remains a constant with a slight magnitude along the rest of the channel wall. For the series microchannel cases, the computational domain was established by adding three surfaces and excluding one region from the rectangular domain. Diffuse effects were observed near the interface of the two segments, where the flow upstream the interface can be either heated or cooled by the flow downstream depending on their temperature difference. In addition, the effect of the gas species was investigated by conducting the simulation using helium and argon respectively. It can be found that the speed of the gas with lighter molecular mass is much higher than that of the heavier gas. The computational domain of the parallel microchannel was established similarly to that of the series microchannel. Under a certain pressure ratio, more pressure drop occurs in the parallel parts as the gap height increases. The recirculation phenomenon was observed after the gap wall between the two parallel parts and was evaluated quantitatively in the present study by defining a parameter called the developing coefficient. The gap height between the two parallel parts has only slight effect of the flow development.
Experimental Study of Drop Deformation and Breakup in a Model Multitoothed Rotor-Stator
Authors: Megias-Alguacil David , Windhab Erich J.
Published: October 2006

The objective of this work is to experimentally study the deformation behavior and breakup process suffered by a droplet submitted to the complex flow developed in a model multitoothed rotor-stator. The studied systems consist of an aqueous solution of polyvinylpyrrolidone in which droplets of diverse silicon oils are dispersed. Experiments are recorded with a digital camera, placed in vertical position, whose images are digitally analyzed. It is found that the drop deformation increases with increasing rotor rotational velocity, showing peaks of deformation corresponding to the proximity of the teeth. Drop breakup is achieved for all studied viscosity ratios. The breakup mechanism depends on the rotor-stator rotational dynamics, with breakup being more effective when the rotor teeth approach the stator teeth.
Reynolds Stress Model in the Prediction of Confined Turbulent Swirling Flows
Authors: Jawarneh Ali M. , Vatistas Georgios H.
Published: October 2006

Strongly swirling vortex chamber flows are examined experimentally and numerically using the Reynolds stress model (RSM). The predictions are compared against the experimental data in terms of the pressure drop across the chamber, the axial and tangential velocity components, and the radial pressure profiles. The overall agreement between the measurements and the predictions is reasonable. The predictions provided by the numerical model show clearly the forced and free vortex modes of the tangential velocity profile. The reverse flow (or back flow) inside the core and near the outlet, known from experiments, is captured by the numerical simulations. The swirl number has been found to have a measurable impact on the flow features. The vortex core size is shown to contract with the swirl number which leads to higher pressure drop, higher peak tangential velocity, and deeper radial pressure profiles near the axis of rotation. The adequate agreement between the experimental data and the simulations using RSM turbulence model provides a valid tool to study further these industrially important swirling flows.
Porphyromonas gingivalis
Genes Involved in Community Development with
Streptococcus gordonii
Authors: Simionato M. Regina , Tucker Chelsea M. , Kuboniwa Masae , Lamont Gwyneth , Demuth Donald R. , Tribble Gena D. , Lamont Richard J.
Published: October 2006

Porphyromonas gingivalis
, one of the causative agents of adult periodontitis, develops biofilm microcolonies on substrata of
Streptococcus gordonii
but not on
Streptococcus mutans. P. gingivalis
genome microarrays were used to identify genes differentially regulated during accretion of
P. gingivalis
in heterotypic biofilms with
S. gordonii
. Thirty-three genes showed up- or downregulation by array analysis, and differential expression was confirmed by quantitative reverse transcription-PCR. The functions of the regulated genes were predominantly related to metabolism and energy production. In addition, many of the genes have no current known function. The roles of two upregulated genes,
ftsH
(PG0047) encoding an ATP-dependent zinc metallopeptidase and
ptpA
(PG1641) encoding a putative tyrosine phosphatase, were investigated further by mutational analysis. Strains with mutations in these genes developed more abundant biofilms with
S. gordonii
than the parental strain developed.
ftsH
and
ptpA
may thus participate in a regulatory network that constrains
P. gingivalis
accumulation in heterotypic biofilms. This study provided a global analysis of
P. gingivalis
transcriptional responses in an oral microbial community and also provided insight into the regulation of heterotypic biofilm development.
Role of
lgtC
in Resistance of Nontypeable
Haemophilus influenzae
Strain R2866 to Human Serum
Authors: Erwin Alice L. , Allen Simon , Ho Derek K. , Bonthius Paul J. , Jarisch Justin , Nelson Kevin L. , Tsao David L. , Unrath William C. T. , Watson Michael E. , Gibson Bradford W. , Apicella Michael A. , Smith Arnold L.
Published: October 2006

We are investigating a nontypeable
Haemophilus influenzae
(NTHI) strain, R2866, isolated from a child with meningitis. R2866 is unusually resistant to killing by normal human serum. The serum 50% inhibitory concentration (IC
50
) for this strain is 18%, approaching that of encapsulated
H. influenzae
. R3392 is a derivative of R2866 that was found to have increased sensitivity to human serum (IC
50
, 1.5%). Analysis of tetrameric repeat regions within lipooligosaccharide (LOS) biosynthetic genes in both strains indicated that the glycosyltransferase gene
lgtC
was out of frame (“off”) in most colonies of R3392 but in frame with its start codon (“on”) in most colonies of the parent. We sought antigenic and biochemical evidence for modification of the LOS structure. In a whole-cell enzyme-linked immunosorbent assay, strain R3392 displayed reduced binding of the Galα1,4Gal-specific monoclonal antibody 4C4. Mass spectrometry analysis of LOS from strain R2866 indicated that the primary oligosaccharide glycoform contained four heptose and four hexose residues, while that of R3392 contained four heptose and three hexose residues. We conclude that the R2866
lgtC
gene encodes a galactosyltransferase involved in synthesis of the 4C4 epitope, as in other strains, and that expression of
lgtC
is associated with the high-level serum resistance that has been observed for this strain. This is the first description of the genetic basis of high-level serum resistance in NTHI, as well as the first description of LOS composition in an NTHI strain for which the complete genome sequence has been determined.
Complex Role of Hemoglobin and Hemoglobin-Haptoglobin Binding Proteins in
Haemophilus influenzae
Virulence in the Infant Rat Model of Invasive Infection
Authors: Seale Thomas W. , Morton Daniel J. , Whitby Paul W. , Wolf Roman , Kosanke Stanley D. , VanWagoner Timothy M. , Stull Terrence L.
Published: October 2006

Haemophilus influenzae
requires an exogenous heme source for aerobic growth in vitro. Hemoglobin or hemoglobin-haptoglobin satisfies this requirement. Heme acquisition from hemoglobin-haptoglobin is mediated by proteins encoded by
hgp
genes. Both Hgps and additional proteins, including those encoded by the
hxu
operon, provide independent pathways for hemoglobin utilization. Recently we showed that deletion of the set of three
hgp
genes from a nontypeable strain (86-028NP) of
H. influenzae
attenuated virulence in the chinchilla otitis media model of noninvasive disease. The present study was undertaken to investigate the role of the
hgp
genes in virulence of the wild-type serotype b clinical isolate HI689 in the infant rat model of hematogenous meningitis, an established model of invasive disease requiring aerobic growth. Bacteremia of high titer and long duration (>14 days) and histopathologically confirmed meningitis occurred in >95% of infant rats challenged at 5 days of age with strain HI689. While mutations disrupting either the Hgp- or Hxu-mediated pathway of heme acquisition had no effect on virulence in infant rats, an isogenic mutant deficient for both pathways was unable to sustain bacteremia or produce meningitis. In contrast, mutations disrupting either pathway decreased the limited ability of
H. influenzae
to initiate and sustain bacteremia in weanling rats. Biochemical and growth studies also indicated that infant rat plasma contains multiple heme sources that change with age. Taken together, these data indicate that both the
hgp
genes and the
hxuC
gene are virulence determinants in the rat model of human invasive disease.
Clinical and Pathologic Changes in a Guinea Pig Aerosol Challenge Model of Acute Q Fever
Authors: Russell-Lodrigue K. E. , Zhang G. Q. , McMurray D. N. , Samuel J. E.
Published: October 2006

Acute Q fever is a zoonotic disease caused by the obligate intracellular bacterium
Coxiella burnetii
and can manifest as a flu-like illness, pneumonia, or hepatitis. A need exists in Q fever research for animal models mimicking both the typical route of infection (inhalation) and the clinical illness seen in human cases of Q fever. A guinea pig aerosol challenge model was developed using
C. burnetii
Nine Mile phase I (RSA 493), administered using a specialized chamber designed to deliver droplet nuclei directly to the alveolar spaces. Guinea pigs were given 10
1
to 10
6
organisms and evaluated for 28 days postinfection. Clinical signs included fever, weight loss, respiratory difficulty, and death, with the degree and duration of response corresponding to the dose of organism delivered. Histopathologic evaluation of the lungs of animals infected with a high dose showed coalescing panleukocytic bronchointerstitial pneumonia at 7 days postinfection that resolved to multifocal lymphohistiocytic interstitial pneumonia by 28 days. Guinea pigs receiving a killed whole-cell vaccine prior to challenge with the highest dose of
C. burnetii
were protected against lethal infection and did not develop fever. Clinical signs and pathological changes noted for these guinea pigs were comparable to those seen in human acute Q fever, making this an accurate and valuable animal model of human disease.
Serologic Evidence for Effective Production of Cytolysin A in
Salmonella enterica
Serovars Typhi and Paratyphi A during Human Infection
Authors: von Rhein Christine , Hunfeld Klaus-Peter , Ludwig Albrecht
Published: October 2006

ClyA
STy
and ClyA
SPaA
are closely related pore-forming cytolysins of
Salmonella enterica
serovars Typhi and Paratyphi A whose expression is strongly repressed under standard in vitro growth conditions. We show here that human infections by these pathogens cause a specific antibody response to ClyA, indicating effective toxin production during infection.
Role of Host Protein Tyrosine Phosphatase SHP-1 inLeishmania donovani-Induced Inhibition of Nitric Oxide Production
Authors: Forget Geneviève , Gregory David J. , Whitcombe Lorie A. , Olivier Martin
Published: October 2006

In order to survive within the macrophages of its host organism, the protozoan parasiteLeishmaniainhibits a number of critical, gamma interferon (IFN-γ)-inducible, macrophage functions, including the generation of nitric oxide. We have previously shown that the protein tyrosine phosphatase SHP-1 (Src-homology 2 domain containing phosphatase-1) is activated duringLeishmaniainfection and plays an important role in both the survival ofLeishmaniawithin cultured macrophages and disease progression in vivo by inhibiting nitric oxide production. Here we use a SHP-1−/−macrophage cell line derived frommotheatenmice to address the mechanisms by which SHP-1 prevents IFN-γ-dependent nitric oxide production duringLeishmania donovaniinfection. We show thatLeishmaniainhibits nitric oxide production in response to IFN-γ poorly in SHP-1-deficient macrophages. This correlates with the inability ofLeishmaniato alter JAK2 and mitogen-activated protein kinase extracellular signal-regulated kinase 1 and 2 (ERK1/2) phosphorylation and to prevent nuclear translocation of transcription factors NF-κB and AP-1, although the latter two to a lesser extent. Surprisingly,Leishmaniainactivated the transcription factor STAT1 to a similar extent in SHP-1-deficient and wild-type macrophages, so STAT1 is not necessary for nitric oxide production by infected macrophages. Overall, this study demonstrates that induction of SHP-1 byLeishmaniais vital for inhibition of nitric oxide generation and that this inhibition occurs through the inactivation of JAK2 and ERK1/2, and transcription factors NF-κB and AP-1.
Penicillin-Binding Protein 1a Promotes Resistance of Group B Streptococcus to Antimicrobial Peptides
Authors: Hamilton Andrea , Popham David L. , Carl David J. , Lauth Xavier , Nizet Victor , Jones Amanda L.
Published: October 2006

Evasion of host immune defenses is critical for the progression of invasive infections caused by the leading neonatal pathogen, group B streptococcus (GBS). Upon characterizing the factors required for virulence in a neonatal rat sepsis model, we found that a surface-associated penicillin-binding protein (PBP1a), encoded byponA, played an essential role in resistance of GBS to phagocytic clearance. In order to elucidate how PBP1a promotes resistance to innate immunity, we compared the susceptibility of wild-type GBS and an isogenicponAmutant to the bactericidal components of human neutrophils. The isogenic strains were found to be equally capable of blocking complement activation on the bacterial surface and equally associated with phagocytes and susceptible to oxidative killing. In contrast, theponAmutant was significantly more susceptible to killing by cationic antimicrobial peptides (AMPs) of the cathelicidin and defensin families, which are now recognized as integral components of innate host defense against invasive bacterial infection. These observations may help explain the sensitivity to phagocytic killing and attenuated virulence of theponAmutant. This novel function for PBP1a in promoting resistance of GBS to AMP did not involve an alteration in bacterial surface charge or peptidoglycan cross-linking. While the peptidoglycan polymerization and cross-linking activity of PBPs are essential for bacterial survival, our study is the first to identify a role for a PBP in resistance to host AMPs.
Discordance in the Effects ofYersinia pestison the Dendritic Cell Functions Manifested by Induction of Maturation and Paralysis of Migration
Authors: Velan Baruch , Bar-Haim Erez , Zauberman Ayelet , Mamroud Emanuelle , Shafferman Avigdor , Cohen Sara
Published: October 2006

The encounter between invading microorganisms and dendritic cells (DC) triggers a series of events which include uptake and degradation of the microorganism, induction of a maturation process, and enhancement of DC migration to the draining lymph nodes. Various pathogens have developed strategies to counteract these events as a measure to evade the host defense. In the present study we found that interaction of theYersinia pestisEV76 strain with DC has no effect on cell viability and is characterized by compliance with effective maturation, which is manifested by surface display of major histocompatibility complex class II, of costimulatory markers, and of the chemokine receptor CCR7. This is in contrast to maturation inhibition and cell death induction exerted by the related speciesYersinia enterocoliticaWA O:8.Y. pestisinteractions with DC were found, however, to impair functions related to cytoskeleton rearrangement. DC pulsed withY. pestisfailed to adhere to solid surfaces and to migrate toward the chemokine CCL19 in an in vitro transmembrane assay. Both effects were dependent on the presence of the pCD1 virulence plasmid and on a bacterial growth shift to 37°C prior to infection. Moreover, while instillation of a pCD1-curedY. pestisstrain into mouse airways triggered effective transport of alveolar DC to the mediastinal lymph node, instillation ofY. pestisharboring the plasmid failed to do so. Taken together, these results suggest that virulence plasmid-dependent impairment of DC migration is the major mechanism utilized byY. pestisto subvert DC function.
Protease Activity, Secretion, Cell Entry, Cytotoxicity, and Cellular Targets of Secreted Autotransporter Toxin of Uropathogenic
Escherichia coli
Authors: Maroncle Nathalie M. , Sivick Kelsey E. , Brady Rebecca , Stokes Faye-Ellen , Mobley Harry L. T.
Published: October 2006

The secreted autotransporter toxin (Sat), found predominantly in uropathogenic
Escherichia coli
, is a member of the SPATE (serine protease autotransporters of
Enterobacteriaceae
) family and, as such, has serine protease activity and causes cytopathic effects on various cell types. To assess the contribution of the serine protease active site to the mechanism of action of Sat, mutations were made in the first (S256I), in the second (S258A), or in both (S256I/S258A) serine residues within the active site motif. Mutations in the first or both serines reduced protease activity to background levels (
P
< 0.001); a single mutation in the second serine reduced activity by 60% compared to wild type (
P
< 0.001). After reversion of the S256I mutation to wild type (I256S), we confirmed S
256
as the catalytically active serine. None of these mutations affected secretion of the mature passenger domain or release into the supernatant. The S256I mutation, however, abrogated the cytotoxicity of Sat on human bladder (UM-UC-3) and kidney (HEK 293) epithelial cells, characterized by rounding and elongation, respectively, and a high level of cell detachment. Moreover, S
256
is essential for Sat to mediate cytoskeletal contraction and actin loss in host cells as well as to degrade specific membrane/cytoskeletal (fodrin and leukocyte function-associated molecule 1) and nuclear [microtubule-associated proteins, LIM domain-only protein 7, Rap GTPase-activating protein, poly(ADP-ribose) polymerase] proteins in vitro. Lastly, Sat was internalized by host cells and localized to the cytoskeletal fraction where membrane/cytoskeletal target proteins reside.
Cytosolic Entry Controls CD8+-T-Cell Potency during Bacterial Infection
Authors: Bahjat Keith S. , Liu Weiqun , Lemmens Edward E. , Schoenberger Stephen P. , Portnoy Daniel A. , Dubensky Thomas W. , Brockstedt Dirk G.
Published: October 2006

Interaction with host immunoreceptors during microbial infection directly impacts the magnitude of the ensuing innate immune response. How these signals affect the quality of the adaptive T-cell response remains poorly understood. Utilizing an engineered strain of the intracellular pathogenListeria monocytogenesthat infects cells but fails to escape from the phagosome, we demonstrate the induction of long-lived memory T cells that are capable of secondary expansion and effector function but are incapable of providing protective immunity. We demonstrate that microbial invasion of the cytosol is required for dendritic cell activation and integration of CD40 signaling, ultimately determining the ability of the elicited CD8+-T-cell pool to protect against lethal wild-typeL. monocytogeneschallenge. These results reveal a crucial role for phagosomal escape, not for delivery of antigen to the class I major histocompatibility complex pathway but for establishing the appropriate cellular context during CD8+-T-cell priming.
The Innate Immune Responses of Colonic Epithelial Cells toTrichuris murisAre Similar in Mouse Strains That Develop a Type 1 or Type 2 Adaptive Immune Response
Authors: deSchoolmeester Matthew L. , Manku Harinder , Else Kathryn J.
Published: October 2006

Trichuris murisresides in intimate contact with its host, burrowing within cecal epithelial cells. However, whether the enterocyte itself responds innately toT. murisis unknown. This study investigated for the first time whether colonic intestinal epithelial cells (IEC) produce cytokines or chemokines followingT. murisinfection and whether divergence of the innate response could explain differentially polarized adaptive immune responses in resistant and susceptible mice. Increased expression of mRNA for the proinflammatory cytokines gamma interferon (IFN-γ) and tumor necrosis factor and the chemokine CCL2 (MCP-1) were seen after infection of susceptible and resistant strains, with the only difference in expression being a delayed increase in CCL2 in BALB/c IEC. These increases were ablated in MyD88−/−mice, and NF-κB p65 was phosphorylated in response toT. murisexcretory/secretory products in the epithelial cell line CMT-93, suggesting involvement of the MyD88-NF-κB signaling pathway in IEC cytokine expression. These data reveal that IEC respond innately toT. muris. However, the minor differences identified between resistant and susceptible mice are unlikely to underlie the subsequent development of a susceptible type 1 (IFN-γ-dominated) or resistant type 2 (interleukin-4 [IL-4]/IL-13-dominated) adaptive immune response.
Occupational exposure in dentistry and miscarriage
Authors: Lindbohm Marja-Liisa , Ylöstalo Pekka , Sallmén Markku , Henriks-Eckerman Maj-Len , Nurminen Tuula , Forss Helena , Taskinen Helena
Published: October 2006

Background:Information on the reproductive effects of chemical exposures in dental work is sparse or inconsistent.

Aim:To investigate whether dental workers exposed to acrylate compounds, mercury amalgam, solvents or disinfectants are at an increased risk of miscarriage.

Methods:The study was conducted among women dental workers and a comparison group of workers occupationally unexposed to dental restorative materials. Information on pregnancies was obtained from national registers and outpatient units of hospitals. Data on occupational exposure were obtained using postal questionnaires. The final study population included 222 cases of miscarriage and 498 controls (births). An occupational hygienist assessed exposure to acrylate compounds, disinfectants and solvents. Exposure to other agents was assessed on the basis of the questionnaire data. Odds ratios (ORs) and confidence intervals (CIs) were estimated using conditional logistic regression.

Results:The ORs adjusted for confounding factors were increased for moderate-exposure and high-exposure categories of mercury amalgam (OR 2.0, 95% CI 1.0 to 4.1 and OR 1.3, 95% CI 0.6 to 2.5, respectively). The risk was slightly increased for the highest-exposure category of 2-hydroxyethylmethacrylate (OR 1.4, 95% CI 0.7 to 2.6) and polymethylmethacrylate dust (OR 1.4, 95% CI 0.8 to 2.4). A slightly increased risk was also detected for likely exposure to organic solvents (OR 1.4, 95% CI 0.8 to 2.3) and disinfectants (OR 1.5, 95% CI 0.9 to 2.7).

Conclusions:No strong association or consistent dose–response relationship was observed between exposure to chemical agents in dental work and the risk of miscarriage. A slightly increased risk was found for exposure to mercury amalgam, some acrylate compounds, solvents and disinfectants. These findings indicate that the possibility of a weak association between exposure to these agents and an increased risk of miscarriage cannot be excluded.
NEWTONIAN MECHANICS OF NEUTRON SUPERFLUID IN ELASTIC STAR CRUST
Authors: CARTER BRANDON , CHACHOUA ELIE
Published: October 2006

To account for pulsar frequency glitches, it is necessary to use a neutron star crust model allowing not only for neutron superfluidity but also for elastic solidity. These features have been treated separately in previous treatments of crust matter, but are combined here in a unified treatment that is based on the use of a Lagrangian master functon, so that the system is ensured coherence by the relevant Noether identities. Besides the model obtained directly from the variation principle, the same master function can provide other conservative alternatives, allowing in particular for the effect of perfect vortex pinning. It is also shown how such models can be generalized to allow for dissipative effects, including that of imperfect pinning, meaning vortex drag or creep.
FOLIATION OF THE SCHWARZSCHILD AND REISSNER–NORDSTRÖM SPACE–TIMES BY FLAT SPACE-LIKE HYPERSURFACES
Authors: QADIR ASGHAR , SIDDIQUI AZAD A.
Published: October 2006

It is known that spherically symmetric space–times admit flat space-like foliations. In this paper a simple procedure for the complete foliation of the Schwarzschild space–time by flat space-like hypersurfaces is developed, using the fact that unforced geodesics are orthogonal to such hypersurfaces. The method is then extended to obtain a complete foliation of the Reissner–Nordström space–time by such hypersurfaces. In this case, as there is a barrier beyond which the geodesics do not go, a complete foliation is obtained by analytically continuing the hypersurfaces beyond the barrier. A duality between imaginary time-like geodesics and space-like hypersurfaces is noted, which also provides complete foliation — but the hypersurfaces are not flat. The features of our foliation are discussed.