bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating Gas Turbines for Process Applications: Economic Guides for the Decision Maker
Authors: Koubek J. H. , Kovacik J. M.
Published: April 2015

The purpose of this paper is to discuss several economic factors commonly used in the evaluation of equipment for the industrial user. The effect of major operating and fixed cost variables is illustrated. Also included are several curves which permit rapid evaluation of net payout, end of period cumulative net cash flow, and discounted rate of return after Federal income taxes once the gross payout period has been established. The application of these economic factors and investment criteria are illustrated by use of an example comparing two energy supply systems for a process requiring both power and heat.
Designing Rotor Burst Protection
Authors: Martino A. A.
Published: April 2015

The integrated theoretical and experimental efforts of the Rotor Burst Protection Program (RBPP) are providing the needed design data and material evaluations to assist any turbomachine manufacturers to provide satisfactory, protective systems without imposing large weight penalties on the equipment. The need for the RBPP is clearly indicated by the uncontained failure statistics included. Experimental observations are made relative to such important factors as fragment type, blade effects, ring plastic growth, ring restraint, fragment energy distribution, ring cross section, and radial clearance. Transient ring response computer codes being developed by the Massachusetts Institute of Technology are described.
“Flying Test Cell” Evaluation and Applications
Authors: Esser J. R.
Published: April 2015

This paper discusses the test results of an automatic, real-time Engine Performance Monitoring System (EPMS) which was flight tested on-board a commercial airline B-707-321B aircraft. EPMS employed the steady-state technique used in test cells to determine the “health” of the operating jet engine. Additional techniques and applications being developed by Emerson Electric Co., such as the portable ground based jet engine analyzer and the NAVY Jet Engine Transient Health Analyses Study, are also discussed.
Heavy Oil or Residual Oil: New Opportunity for the Utility Gas Turbine
Authors: Vermes Géza
Published: April 2015

The newly enacted requirements of desulfurization brought about a sudden change in the fuel market of the industrial gas turbine: oils became available at a price considerably below that of distillate oils. These oils present a new option for the gas turbine industry to avoid the difficulties of the lower priced residuals, without the high cost of the No. 2-GT distillate. Work performed by the author’s company to introduce these oils is presented in this paper.
Holographic Analysis of Turbine Blades
Authors: Waters J. P. , Aas H. G.
Published: April 2015

Holographic techniques have been employed to study various turbine blade characteristics. The studies were performed using both helium-neon continuous wave (CW) and ruby pulse lasers to generate static double-exposure (CW), dynamic time-average (CW), or dynamic double-exposure (pulsed) interferometric holograms. In general, the interferometric holograms reconstruct the turbine blades in two different states of stress and produce a set of bright and dark interference fringes (on the reconstructed image) which represent contours of equal surface displacement. The turbine blade was stressed in several ways. The displacement contours obtained were used to define and evaluate characteristics of the blade. Described in detail are results of holographic surface strain measurements made on both solid and hollow turbine blades. Comparisons are also made with conventional strain gage measurements. A review of the resonant modes present on turbine blades and an analysis of the resulting interferometric fringe patterns are made. Vibrational excitation, of up to 45,000 Hz, is examined. Also included are preliminary results of studies for inspecting hollow turbine blades using internal pressurization as a means for detecting internal damage or flaws; and for obtaining a qualitative measure of turbine wall thickness using acoustic vibration. Finally, results of an experimental investigation concerned with the effects of temperature on turbine blade holography are described and principal results reviewed.
Design and Development of a Boron-Glass-Epoxy Lightweight Composite Gear Case
Authors: Holcomb W. N.
Published: April 2015

The design and development of a composite material front housing for the reduction gear of the T56 engine are discussed. The program was undertaken to advance the state-of-the-art in engine structures by making a material available that is capable of replacing aluminum and magnesium. The selected boron-glass-epoxy material exhibits high strength and specific stiffness, light weight, good corrosion resistance, and suitability for molding. The design, molding, machining, and testing phases of the programs are described.
Properties of bottom and top channel interfaces in double-gate back-channel-etched amorphous indium-gallium-zinc oxide thin-film transistors
Authors: Jeong Chan-Yong , Lee Daeun , Song Sang-Hun , Kim Jong In , Lee Jong-Ho , Um Jae-Gwang , Jang Jin , Kwon Hyuck-In
Published: April 2015

In this paper, the bottom and top channel interface properties are investigated in the back channel etch-type double-gate amorphous indium–gallium–zinc oxide (a-IGZO) thin-film transistors. The authors apply the subthreshold technique by depleting one channel, while sweeping the gate voltage of the opposite channel to separately characterize the bottom and top channel interfaces. The extracted surface energy distribution of the bottom and top channel interface trap densities is well fitted with an exponential distribution, and the top channel interface trap density is found to be around 2.5 times greater than that of the bottom channel interface at the conduction band edge. This is mainly attributed to the poor quality of the top gate SiOx insulator owing to the low plasma-enhanced chemical vapor deposition temperature or to the defect generation at the back surface of the a-IGZO caused by the plasma damage during the top gate SiOx insulator deposition. The electrons are shown to be more easily trapped at the top channel interface than at the bottom channel interface under high gate bias stresses in the fabricated back channel etch-type double-gate a-IGZO thin-film transistors.
Acoustical transmission-line model of the middle-ear cavities and mastoid air cells
Authors: Keefe Douglas H.
Published: April 2015

An acoustical transmission line model of the middle-ear cavities and mastoid air cell system (MACS) was constructed for the adult human middle ear with normal function. The air-filled cavities comprised the tympanic cavity, aditus, antrum, and MACS. A binary symmetrical airway branching model of the MACS was constructed using an optimization procedure to match the average total volume and surface area of human temporal bones. The acoustical input impedance of the MACS was calculated using a recursive procedure, and used to predict the input impedance of the middle-ear cavities at the location of the tympanic membrane. The model also calculated the ratio of the acoustical pressure in the antrum to the pressure in the middle-ear cavities at the location of the tympanic membrane. The predicted responses were sensitive to the magnitude of the viscothermal losses within the MACS. These predicted input impedance and pressure ratio functions explained the presence of multiple resonances reported in published data, which were not explained by existing MACS models.
Cognitive predictors of perceptual adaptation to accented speech
Authors: Banks Briony , Gowen Emma , Munro Kevin J. , Adank Patti
Published: April 2015

The present study investigated the effects of inhibition, vocabulary knowledge, and working memory on perceptual adaptation to accented speech. One hundred young, normal-hearing adults listened to sentences spoken in a constructed, unfamiliar accent presented in speech-shaped background noise. Speech Reception Thresholds (SRTs) corresponding to 50% speech recognition accuracy provided a measurement of adaptation to the accented speech. Stroop, vocabulary knowledge, and working memory tests were performed to measure cognitive ability. Participants adapted to the unfamiliar accent as revealed by a decrease in SRTs over time. Better inhibition (lower Stroop scores) predicted greater and faster adaptation to the unfamiliar accent. Vocabulary knowledge predicted better recognition of the unfamiliar accent, while working memory had a smaller, indirect effect on speech recognition mediated by vocabulary score. Results support a top-down model for successful adaptation to, and recognition of, accented speech; they add to recent theories that allocate a prominent role for executive function to effective speech comprehension in adverse listening conditions.
Modeling local active sound control with remote sensors in spatially random pressure fields
Authors: Elliott Stephen J. , Cheer Jordan
Published: April 2015

A general formulation is presented for the optimum controller in an active system for local sound control in a spatially random primary field. The sound field in a control region is selectively attenuated using secondary sources, driven by reference sensors, all of which are potentially remote from this control region. It is shown that the optimal controller is formed of the combination of a least-squares estimation of the primary source signals from the reference signals, and a least-squares controller driven by the primary source signals themselves. The optimum controller is also calculated using the remote microphone technique, in both the frequency and the time domains. The sound field under control is assumed to be stationary and generated by an array of primary sources, whose source strengths are specified using a spectral density matrix. This can easily be used to synthesize a diffuse primary field, if the primary sources are uncorrelated and far from the control region, but can also generate primary fields dominated by contributions from a particular direction, for example, which is shown to significantly affect the shape of the resulting zone of quiet.
A numerical investigation on the vortex formation and flow separation of the oscillatory flow in jet pumps
Authors: Oosterhuis Joris P. , Bühler Simon , van der Meer Theo H. , Wilcox Douglas
Published: April 2015

A two-dimensional computational fluid dynamics model is used to predict the oscillatory flow through a tapered cylindrical tube section (jet pump) placed in a larger outer tube. Due to the shape of the jet pump, an asymmetry in the hydrodynamic end effects will exist which will cause a time-averaged pressure drop to occur that can be used to cancel Gedeon streaming in a closed-loop thermoacoustic device. The performance of two jet pump geometries with different taper angles is investigated. A specific time-domain impedance boundary condition is implemented in order to simulate traveling acoustic wave conditions. It is shown that by scaling the acoustic displacement amplitude to the jet pump dimensions, similar minor losses are observed independent of the jet pump geometry. Four different flow regimes are distinguished and the observed flow phenomena are related to the jet pump performance. The simulated jet pump performance is compared to an existing quasi-steady approximation which is shown to only be valid for small displacement amplitudes compared to the jet pump length.
Analyzing panel acoustic contributions toward the sound field inside the passenger compartment of a full-size automobile
Authors: Wu Sean F. , Moondra Manmohan , Beniwal Ravi
Published: April 2015

The Helmholtz equation least squares (HELS)-based nearfield acoustical holography (NAH) is utilized to analyze panel acoustic contributions toward the acoustic field inside the interior region of an automobile. Specifically, the acoustic power flows from individual panels are reconstructed, and relative contributions to sound pressure level and spectrum at any point of interest are calculated. Results demonstrate that by correlating the acoustic power flows from individual panels to the field acoustic pressure, one can correctly locate the panel allowing the most acoustic energy transmission into the vehicle interior. The panel on which the surface acoustic pressure amplitude is the highest should not be used as indicative of the panel responsible for the sound field in the vehicle passenger compartment. Another significant advantage of this HELS-based NAH is that measurements of the input data only need to be taken once by using a conformal array of microphones in the near field, and ranking of panel acoustic contributions to any field point can be readily performed. The transfer functions between individual panels of any vibrating structure to the acoustic pressure anywhere in space are calculated not measured, thus significantly reducing the time and effort involved in panel acoustic contributions analyses.
Self-entrainment of the right and left vocal fold oscillators
Authors: Lucero Jorge C. , Schoentgen Jean , Haas Jessy , Luizard Paul , Pelorson Xavier
Published: April 2015

This article presents an analysis of entrained oscillations of the right and left vocal folds in the presence of asymmetries. A simple one-mass model is proposed for each vocal fold. A stiffness asymmetry and open glottis oscillations are considered first, and regions of oscillation are determined by a stability analysis and an averaging technique. The results show that the subglottal threshold pressure for 1:1 entrainment increases with the asymmetry. Within that region, both folds oscillate with the same amplitude and with the lax fold delayed in time with regard to the tense fold. At large asymmetries, a region involving several different phase entrainments or toroidal regimes at constant threshold pressure appears. The effect of vocal fold collisions and asymmetry in the damping coefficients of the oscillators are explored next by means of numerical analyses. It is shown that the damping asymmetry expands the 1:1 entrainment region at low subglottal pressures across the whole asymmetry range. In the expanded region, the oscillator with the lowest natural frequency is dominant and the other oscillator has a large phase advance and small amplitude. The theoretical results are finally compared with data collected from a mechanical replica of the vocal folds.
Acoustic coupled fluid–structure interactions using a unified fast multipole boundary element method
Authors: Wilkes Daniel R. , Duncan Alec J.
Published: April 2015

This paper presents a numerical model for the acoustic coupled fluid–structure interaction (FSI) of a submerged finite elastic body using the fast multipole boundary element method (FMBEM). The Helmholtz and elastodynamic boundary integral equations (BIEs) are, respectively, employed to model the exterior fluid and interior solid domains, and the pressure and displacement unknowns are coupled between conforming meshes at the shared boundary interface to achieve the acoustic FSI. The low frequency FMBEM is applied to both BIEs to reduce the algorithmic complexity of the iterative solution from O(N2) to O(N1.5) operations per matrix–vector product for N boundary unknowns. Numerical examples are presented to demonstrate the algorithmic and memory complexity of the method, which are shown to be in good agreement with the theoretical estimates, while the solution accuracy is comparable to that achieved by a conventional finite element-boundary element FSI model.
Categorical loudness scaling and equal-loudness contours in listeners with normal hearing and hearing loss
Authors: Rasetshwane Daniel M. , Trevino Andrea C. , Gombert Jessa N. , Liebig-Trehearn Lauren , Kopun Judy G. , Jesteadt Walt , Neely Stephen T. , Gorga Michael P.
Published: April 2015

This study describes procedures for constructing equal-loudness contours (ELCs) in units of phons from categorical loudness scaling (CLS) data and characterizes the impact of hearing loss on these estimates of loudness. Additionally, this study developed a metric, level-dependent loudness loss, which uses CLS data to specify the deviation from normal loudness perception at various loudness levels and as function of frequency for an individual listener with hearing loss. CLS measurements were made in 87 participants with hearing loss and 61 participants with normal hearing. An assessment of the reliability of CLS measurements was conducted on a subset of the data. CLS measurements were reliable. There was a systematic increase in the slope of the low-level segment of the CLS functions with increase in the degree of hearing loss. ELCs derived from CLS measurements were similar to standardized ELCs (International Organization for Standardization, ISO 226:2003). The presence of hearing loss decreased the vertical spacing of the ELCs, reflecting loudness recruitment and reduced cochlear compression. Representing CLS data in phons may lead to wider acceptance of CLS measurements. Like the audiogram that specifies hearing loss at threshold, level-dependent loudness loss describes deficit for suprathreshold sounds. Such information may have implications for the fitting of hearing aids.
Separable spectro-temporal Gabor filter bank features: Reducing the complexity of robust features for automatic speech recognition
Authors: Schädler Marc René , Kollmeier Birger
Published: April 2015

To test if simultaneous spectral and temporal processing is required to extract robust features for automatic speech recognition (ASR), the robust spectro-temporal two-dimensional-Gabor filter bank (GBFB) front-end from Schädler, Meyer, and Kollmeier [J. Acoust. Soc. Am. 131, 4134–4151 (2012)] was de-composed into a spectral one-dimensional-Gabor filter bank and a temporal one-dimensional-Gabor filter bank. A feature set that is extracted with these separate spectral and temporal modulation filter banks was introduced, the separate Gabor filter bank (SGBFB) features, and evaluated on the CHiME (Computational Hearing in Multisource Environments) keywords-in-noise recognition task. From the perspective of robust ASR, the results showed that spectral and temporal processing can be performed independently and are not required to interact with each other. Using SGBFB features permitted the signal-to-noise ratio (SNR) to be lowered by 1.2 dB while still performing as well as the GBFB-based reference system, which corresponds to a relative improvement of the word error rate by 12.8%. Additionally, the real time factor of the spectro-temporal processing could be reduced by more than an order of magnitude. Compared to human listeners, the SNR needed to be 13 dB higher when using Mel-frequency cepstral coefficient features, 11 dB higher when using GBFB features, and 9 dB higher when using SGBFB features to achieve the same recognition performance.
Amplitude fluctuations in a masker influence lexical segmentation in cochlear implant users
Authors: Perry Trevor T. , Kwon Bomjun J.
Published: April 2015

Normal-hearing listeners show masking release, or better speech understanding in a fluctuating-amplitude masker than in a steady-amplitude masker, but most cochlear implant (CI) users consistently show little or no masking release even in artificial conditions where masking release is highly anticipated. The current study examined the hypothesis that the reduced or absent masking release in CI users is due to disruption of linguistic segmentation cues. Eleven CI subjects completed a sentence keyword identification task in a steady masker and a fluctuating masker with dips timed to increase speech availability. Lexical boundary errors in their responses were categorized as consistent or inconsistent with the use of the metrical segmentation strategy (MSS). Subjects who demonstrated masking release showed greater adherence to the MSS in the fluctuating masker compared to subjects who showed little or no masking release, while both groups used metrical segmentation cues similarly in the steady masker. Based on the characteristics of the segmentation cues, the results are interpreted as evidence that CI listeners showing little or no masking release are not reliably segregating speech from competing sounds, further suggesting that one challenge faced by CI users listening in noisy environments is a reduction of reliable segmentation cues.
The equivalent translational compliance of steel or wood studs and resilient channel bars
Authors: Hirakawa Susumu , Davy John L.
Published: April 2015

A number of recent papers have determined the compliance of steel studs for use in models for predicting the sound insulation of cavity stud walls. However, in these papers, the compliance of resilient channel bars on one or both sides of wood studs or on one side of steel studs has not been determined across the whole of the frequency range. The present paper determines the compliance of the combination of resilient channel bars, mounted on wooden or steel studs and modeled as point or as line connections. Steel studs have usually been modeled as line connections. In this paper, they are also modeled as point connections where the points are the screws attaching the wall leaves to the steel studs and individual results rather than average results are analyzed. The compliance that makes Davy's sound insulation predictions agree with experimental sound insulation data was calculated by inverting Davy's equations for sound insulation. Linear regressions of the logarithm of the compliance, against the logarithms of frequency, reduced surface density, cavity depth and number of point connections or stud spacing, were conducted in a low frequency range and in a high frequency range.
Bayesian-based estimation of acoustic surface impedance: Finite difference frequency domain approach
Authors: Bockman Alexander , Fackler Cameron , Xiang Ning
Published: April 2015

Acoustic performance for an interior requires an accurate description of the boundary materials' surface acoustic impedance. Analytical methods may be applied to a small class of test geometries, but inverse numerical methods provide greater flexibility. The parameter estimation problem requires minimizing prediction vice observed acoustic field pressure. The Bayesian-network sampling approach presented here mitigates other methods' susceptibility to noise inherent to the experiment, model, and numerics. A geometry agnostic method is developed here and its parameter estimation performance is demonstrated for an air-backed micro-perforated panel in an impedance tube. Good agreement is found with predictions from the ISO standard two-microphone, impedance-tube method, and a theoretical model for the material. Data by-products exclusive to a Bayesian approach are analyzed to assess sensitivity of the method to nuisance parameters.
Acoustical properties of air-saturated porous material with periodically distributed dead-end pores
Authors: Leclaire P. , Umnova O. , Dupont T. , Panneton R.
Published: April 2015

A theoretical and numerical study of the sound propagation in air-saturated porous media with straight main pores bearing lateral cavities (dead-ends) is presented. The lateral cavities are located at “nodes” periodically spaced along each main pore. The effect of periodicity in the distribution of the lateral cavities is studied, and the low frequency limit valid for the closely spaced dead-ends is considered separately. It is shown that the absorption coefficient and transmission loss are influenced by the viscous and thermal losses in the main pores as well as their perforation rate. The presence of long or short dead-ends significantly alters the acoustical properties of the material and can increase significantly the absorption at low frequencies (a few hundred hertz). These depend strongly on the geometry (diameter and length) of the dead-ends, on their number per node, and on the periodicity along the propagation axis. These effects are primarily due to low sound speed in the main pores and to thermal losses in the dead-end pores. The model predictions are compared with experimental results. Possible designs of materials of a few cm thicknesses displaying enhanced low frequency absorption at a few hundred hertz are proposed.
The stratospheric arrival pair in infrasound propagation
Authors: Waxler Roger , Evers Läslo G. , Assink Jelle , Blom Phillip
Published: April 2015

The ideal case of a deep and well-formed stratospheric duct for long range infrasound propagation in the absence of tropospheric ducting is considered. A canonical form, that of a pair of arrivals, for ground returns of impulsive signals in a stratospheric duct is determined. The canonical form is derived from the geometrical acoustics approximation, and is validated and extended through full wave modeling. The full caustic structure of the field of ray paths is found and used to determine phase relations between the contributions to the wavetrain from different propagation paths. Finally, comparison with data collected from the 2005 fuel gas depot explosion in Buncefield, England is made. The correspondence between the theoretical results and the observations is shown to be quite good.
Gap seal dissipation in linear alternators
Authors: Gonen Eran , Grossman Gershon
Published: April 2015

Earlier models of the coupling between a thermoacoustic system and an electrodynamic motor/alternator considered mechanical damping but ignored the viscous friction and blow-by losses produced by the motor/alternator's piston oscillating within a tight-fitting gap. The model presented here extends previous models to demonstrate that the inclusion of these effects leads to a better estimate of the electroacoustic conversion efficiency and can be used to determine the optimal load resistance for such an alternator's electrical power output. Model predictions were shown to be in excellent agreement with the performance measurements made using two different thermoacoustic engines and using a sealed volume (dummy load) connected to multiple, horizontally opposed motor/alternators, using an empirical determination of the piston-cylinder gap.
Spirituality & Sport: Consulting the Christian Athlete
Authors: Mosley Michael J. , Frierson Desiree’ J. , Cheng Yihan , Aoyagi Mark W.
Published: April 2015

The real world practice of sport and performance psychology will inevitably present the practitioner with performers for whom spirituality is the supreme motivator (Balague, 1999). Spirituality and sport, despite its practical relevance, is an underdeveloped and sometimes misunderstood combination (Nesti, 2007). The aim of this study was to reveal the individual experiences of athletes as they integrate spirituality and their sport participation. Five high level athletes (1 female, 4 male), each holding a Christian worldview were interviewed. A strategically designed interview guide illuminated several key themes, which Watson and Nesti (2005) suggested, would contribute much to the existing literature. Out of these themes, practical implications have been considered for the delivery of sport and performance psychology services to Christian athletes. Evidenced by this study, is the reality that some Christian athletes present a unique perspective through which appropriately tailored sport psychology services can readily precipitate personal excellence in sport and life.
Redundant and specialized roles for diacylglycerol kinases α and ζ in the control of T cell functions
Authors: Mérida Isabel , Andrada Elena , Gharbi Severine I. , Ávila-Flores Antonia
Published: April 2015

Two isoforms of the enzyme that attenuates signaling by the second messenger diacylglycerol regulate multiple properties of T lymphocytes.
Multiple Roles for Enterococcus faecalis Glycosyltransferases in Biofilm-Associated Antibiotic Resistance, Cell Envelope Integrity, and Conjugative Transfer
Authors: Dale Jennifer L. , Cagnazzo Julian , Phan Chi Q. , Barnes Aaron M. T. , Dunny Gary M.
Published: April 2015

The emergence of multidrug-resistant bacteria and the limited availability of new antibiotics are of increasing clinical concern. A compounding factor is the ability of microorganisms to form biofilms (communities of cells encased in a protective extracellular matrix) that are intrinsically resistant to antibiotics.
Enterococcus faecalis
is an opportunistic pathogen that readily forms biofilms and also has the propensity to acquire resistance determinants via horizontal gene transfer. There is intense interest in the genetic basis for intrinsic and acquired antibiotic resistance in
E. faecalis
, since clinical isolates exhibiting resistance to multiple antibiotics are not uncommon. We performed a genetic screen using a library of transposon (Tn) mutants to identify
E. faecalis
biofilm-associated antibiotic resistance determinants. Five Tn mutants formed wild-type biofilms in the absence of antibiotics but produced decreased biofilm biomass in the presence of antibiotic concentrations that were subinhibitory to the parent strain. Genetic determinants responsible for biofilm-associated antibiotic resistance include components of the quorum-sensing system (
fsrA
,
fsrC
, and
gelE
) and two glycosyltransferase (GTF) genes (
epaI
and
epaOX
). We also found that the GTFs play additional roles in
E. faecalis
resistance to detergent and bile salts, maintenance of cell envelope integrity, determination of cell shape, polysaccharide composition, and conjugative transfer of the pheromone-inducible plasmid pCF10. The
epaOX
gene is located in a variable extended region of the enterococcal polysaccharide antigen (
epa
) locus. These data illustrate the importance of GTFs in
E. faecalis
adaptation to diverse growth conditions and suggest new targets for antimicrobial design.
Challenges and Solutions for Clinical Development of New Antibacterial Agents: Results of a Survey among Pharmaceutical Industry Professionals
Authors: Bettiol Esther , Wetherington Jeffrey D. , Schmitt Nicola , Harbarth Stephan
Published: April 2015

As the number of antibacterial medicines in the pipeline remains low, we anonymously surveyed pharmaceutical industry professionals on challenges and solutions for clinical development of these agents. Challenges were reported primarily as financial and regulatory. For multidrug-resistant organisms, there are needs for rapid diagnostic tests, new regulatory guidance, and adaptation of endpoints/trial designs. Regulators and public/private initiatives are addressing these challenges to help ensure that proposed solutions have the support of all involved stakeholders.
Randomized Noninferiority Trial of Dihydroartemisinin-Piperaquine Compared with Sulfadoxine-Pyrimethamine plus Amodiaquine for Seasonal Malaria Chemoprevention in Burkina Faso
Authors: Zongo Issaka , Milligan Paul , Compaore Yves Daniel , Some A. Fabrice , Greenwood Brian , Tarning Joel , Rosenthal Philip J. , Sutherland Colin , Nosten Francois , Ouedraogo Jean-Bosco
Published: April 2015

The WHO recommends that children living in areas of highly seasonal malaria transmission in the Sahel subregion should receive seasonal malaria chemoprevention (SMC) with sulfadoxine-pyrimethamine plus amodiaquine (SPAQ). We evaluated the use of dihydroartemisinin-piperaquine (DHAPQ) as an alternative drug that could be used if SPAQ starts to lose efficacy. A total of 1,499 children 3 to 59 months old were randomized to receive SMC with SPAQ or DHAPQ over 3 months. The primary outcome measure was the risk of clinical malaria (fever or a history of fever with a parasite density of at least 3,000/μl). A cohort of 250 children outside the trial was followed up as a control group. Molecular markers of drug resistance were assessed. The risk of a malaria attack was 0.19 in the DHAPQ group and 0.15 in the SPAQ group, an odds ratio of 1.33 (95% confidence interval [CI], 1.02 to 1.72). Efficacy of SMC compared to the control group was 77% (67% to 84%) for DHAPQ and 83% (74% to 89%) for SPAQ.
pfdhfr
and
pfdhps
mutations associated with antifolate resistance were more prevalent in parasites from children who received SPAQ than in children who received DHAPQ. Both regimens were highly efficacious and well tolerated. DHAPQ is a potential alternative drug for SMC. (This trial is registered at ClinicalTrials.gov under registration no. NCT00941785.)
First Detection of AmpC β-Lactamase
bla
CMY-2
on a Conjugative IncA/C Plasmid in a Vibrio parahaemolyticus Isolate of Food Origin
Authors: Li Ruichao , Lin Dachuan , Chen Kaichao , Wong Marcus Ho Yin , Chen Sheng
Published: April 2015

Vibrio parahaemolyticus
is an important causative agent of gastroenteritis, with the consumption of contaminated seafood being the major transmission route. Resistance to penicillin is common among
V. parahaemolyticus
strains, whereas cephalosporin resistance remains rare. In an attempt to assess the current prevalence and characteristics of antibiotic resistance of this pathogen in common food samples, a total of 54 (17% of the total samples)
V. parahaemolyticus
strains were isolated from 318 meat and seafood samples purchased from supermarkets and wet markets in Shenzhen, China, in 2013. These isolates exhibited high-level resistance to ampicillin, yet they were mostly susceptible to other antimicrobials, except for two that were resistant to extended-spectrum cephalosporins. The β-lactamase gene
bla
PER-1
was detectable in one strain,
V. parahaemolyticus
V43, which was resistant to both third- and fourth-generation cephalosporins. Compared to other
bla
PER-1
-positive
V. parahaemolyticus
strains reported in our previous studies, strain V43 was found to harbor an ∼200-kb conjugative plasmid carrying genes that were different from the antimicrobial resistance genes reported from the previous studies. The β-lactamase gene
bla
CMY-2
was detectable for the first time in another
V. parahaemolyticus
isolate, V4, which was resistant to third-generation cephalosporins. This
bla
CMY-2
gene was shown to be located in an ∼150-kb IncA/C-type conjugative plasmid with a genetic structure consisting of
traB-traV-traA
-IS
Ecp1-bla
CMY-2
-
blc-sugE-encR-orf1-orf2-orf3-orf4-dsbC-traC
, which is identical to that of other IncA/C conjugative plasmids in
Enterobacteriaceae
, albeit with a different size. These findings indicate that the transmission of extended-spectrum-β-lactamase (ESBL) and AmpC β-lactamase genes via conjugative plasmids can mediate the development of extended-spectrum cephalosporin resistance in
V. parahaemolyticus
, thereby posing a potential threat to public health.
A Neutralizing Monoclonal IgG1 Antibody of Platelet-Activating Factor Acetylhydrolase SsE Protects Mice against Lethal Subcutaneous Group A Streptococcus Infection
Authors: Liu Mengyao , Feng Wenchao , Zhu Hui , Lei Benfang
Published: April 2015

Group A
Streptococcus
(GAS) can cause life-threatening invasive infections, including necrotizing fasciitis. There are no effective treatments for severe invasive GAS infections. The platelet-activating factor (PAF) acetylhydrolase SsE produced by GAS is required for invasive GAS to evade innate immune responses and to invade soft tissues. This study determined whether the enzymatic activity of SsE is critical for its function in GAS skin invasion and inhibition of neutrophil recruitment and whether SsE is a viable target for immunotherapy for severe invasive GAS infections. An isogenic derivative of M1T1 strain MGAS5005 producing SsE with an S178A substitution (SsE
S178A
), an enzymatically inactive SsE mutant protein, was generated. This strain induced higher levels of neutrophil infiltration and caused smaller lesions than MGAS5005 in subcutaneous infections of mice. This phenotype is similar to that of MGAS5005
sse
deletion mutants, indicating that the enzymatic activity of SsE is critical for its function. An anti-SsE IgG1 monoclonal antibody (MAb), 2B11, neutralized the PAF acetylhydrolase activity of SsE. Passive immunization with 2B11 increased neutrophil infiltration, reduced skin invasion, and protected mice against MGAS5005 infection. However, 2B11 did not protect mice when it was administered after MGAS5005 inoculation. MGAS5005 induced vascular effusion at infection sites at early hours after GAS inoculation, suggesting that 2B11 did not always have access to infection sites. Thus, the enzymatic activity of SsE mediates its function, and SsE has the potential to be included in a vaccine but is not a therapeutic target. An effective MAb-based immunotherapy for severe invasive GAS infections may need to target virulence factors that are critical for systemic survival of GAS.
Enterococcus faecalis Gelatinase Mediates Intestinal Permeability via Protease-Activated Receptor 2
Authors: Maharshak Nitsan , Huh Eun Young , Paiboonrungruang Chorlada , Shanahan Michael , Thurlow Lance , Herzog Jeremy , Djukic Zorka , Orlando Roy , Pawlinski Rafal , Ellermann Melissa , Borst Luke , Patel Siten , Dotan Iris , Sartor Ryan B. , Carroll Ian M.
Published: April 2015

Microbial protease-mediated disruption of the intestinal epithelium is a potential mechanism whereby a dysbiotic enteric microbiota can lead to disease. This mechanism was investigated using the colitogenic, protease-secreting enteric microbe
Enterococcus faecalis
. Caco-2 and T-84 epithelial cell monolayers and the mouse colonic epithelium were exposed to concentrated conditioned media (CCM) from
E. faecalis
V583 and
E. faecalis
lacking the gelatinase gene (
gelE
). The flux of fluorescein isothiocyanate (FITC)-labeled dextran across monolayers or the mouse epithelium following exposure to CCM from parental or mutant
E. faecalis
strains indicated paracellular permeability. A protease-activated receptor 2 (PAR2) antagonist and PAR2-deficient (PAR2
−/−
) mice were used to investigate the role of this receptor in
E. faecalis
-induced permeability. Gelatinase (GelE) purified from
E. faecalis
V583 was used to confirm the ability of this protease to induce epithelial cell permeability and activate PAR2. The protease-mediated permeability of colonic epithelia from wild-type (WT) and PAR2
−/−
mice by fecal supernatants from ulcerative colitis patients was assessed. Secreted
E. faecalis
proteins induced permeability in epithelial cell monolayers, which was reduced in the absence of
gelE
or by blocking PAR2 activity. Secreted
E. faecalis
proteins induced permeability in the colonic epithelia of WT mice that was absent in tissues from PAR2
−/−
mice. Purified GelE confirmed the ability of this protease to induce epithelial cell permeability via PAR2 activation. Fecal supernatants from ulcerative colitis patients induced permeability in the colonic epithelia of WT mice that was reduced in tissues from PAR2
−/−
mice. Our investigations demonstrate that GelE from
E. faecalis
can regulate enteric epithelial permeability via PAR2.
Overexpression of Porcine Beta-Defensin 2 Enhances Resistance to Actinobacillus pleuropneumoniae Infection in Pigs
Authors: Yang Xi , Cheng Yu-Ting , Tan Mei-Fang , Zhang Hua-Wei , Liu Wan-Quan , Zou Geng , Zhang Liang-Sheng , Zhang Chun-Yan , Deng Si-Min , Yu Lei , Hu Xue-Ying , Li Lu , Zhou Rui
Published: April 2015

To reduce the need for antibiotics in animal production, alternative approaches are needed to control infection. We hypothesized that overexpression of native defensin genes will provide food animals with enhanced resistance to bacterial infections. In this study, recombinant porcine beta-defensin 2 (PBD-2) was overexpressed in stably transfected PK-15 porcine kidney cells. PBD-2 antibacterial activities against
Actinobacillus pleuropneumoniae
, an important respiratory pathogen causing porcine contagious pleuropneumonia, were evaluated on agar plates. Transgenic pigs constitutively overexpressing PBD-2 were produced by a somatic cell cloning method, and their resistance to bacterial infection was evaluated by direct or cohabitation infection with
A. pleuropneumoniae
. Recombinant PBD-2 peptide that was overexpressed in the PK-15 cells showed antibacterial activity against
A. pleuropneumoniae
. PBD-2 was overexpressed in the heart, liver, spleen, lungs, kidneys, and jejunum of the transgenic pigs, which showed significantly lower bacterial loads in the lungs and reduced lung lesions after direct or cohabitation infection with
A. pleuropneumoniae
. The results demonstrate that transgenic overexpression of PBD-2 in pigs confers enhanced resistance against
A. pleuropneumoniae
infection.
Disruption of Parasitehmgb2Gene Attenuates Plasmodium berghei ANKA Pathogenicity
Authors: Briquet Sylvie , Lawson-Hogban Nadou , Boisson Bertrand , Soares Miguel P. , Péronet Roger , Smith Leanna , Ménard Robert , Huerre Michel , Mécheri Salah , Vaquero Catherine
Published: April 2015

Eukaryotic high-mobility-group-box (HMGB) proteins are nuclear factors involved in chromatin remodeling and transcription regulation. When released into the extracellular milieu, HMGB1 acts as a proinflammatory cytokine that plays a central role in the pathogenesis of several immune-mediated inflammatory diseases. We found that thePlasmodiumgenome encodes two genuine HMGB factors,PlasmodiumHMGB1 and HMGB2, that encompass, like their human counterparts, a proinflammatory domain. Given that these proteins are released from parasitized red blood cells, we then hypothesized thatPlasmodiumHMGB might contribute to the pathogenesis of experimental cerebral malaria (ECM), a lethal neuroinflammatory syndrome that develops in C57BL/6 (susceptible) mice infected withPlasmodium bergheiANKA and that in many aspects resembles human cerebral malaria elicited byP. falciparuminfection. The pathogenesis of experimental cerebral malaria was suppressed in C57BL/6 mice infected withP. bergheiANKA lacking thehmgb2gene (Δhmgb2ANKA), an effect associated with a reduction of histological brain lesions and with lower expression levels of several proinflammatory genes. The incidence of ECM inpbhmgb2-deficient mice was restored by the administration of recombinantPbHMGB2. Protection from experimental cerebral malaria in Δhmgb2ANKA-infected mice was associated with reduced sequestration in the brain of CD4+and CD8+T cells, including CD8+granzyme B+and CD8+IFN-γ+cells, and, to some extent, neutrophils. This was consistent with a reduced parasite sequestration in the brain, lungs, and spleen, though to a lesser extent than in wild-typeP. bergheiANKA-infected mice. In summary,PlasmodiumHMGB2 acts as an alarmin that contributes to the pathogenesis of cerebral malaria.
S-Inosyl-l-Homocysteine Hydrolase, a Novel Enzyme Involved inS-Adenosyl-l-Methionine Recycling
Authors: Miller Danielle , Xu Huimin , White Robert H.
Published: April 2015

S-Adenosyl-l-homocysteine, the product ofS-adenosyl-l-methionine (SAM) methyltransferases, is known to be a strong feedback inhibitor of these enzymes. A hydrolase specific forS-adenosyl-l-homocysteine producesl-homocysteine, which is remethylated to methionine and can be used to regenerate SAM. Here, we show that the annotatedS-adenosyl-l-homocysteine hydrolase inMethanocaldococcus jannaschiiis specific for the hydrolysis and synthesis ofS-inosyl-l-homocysteine, notS-adenosyl-l-homocysteine. This is the first report of an enzyme specific forS-inosyl-l-homocysteine. As withS-adenosyl-l-homocysteine hydrolase, which shares greater than 45% sequence identity with theM. jannaschiihomologue, theM. jannaschiienzyme was found to copurify with bound NAD+and hasKmvalues of 0.64 ± 0.4 mM, 0.0054 ± 0.006 mM, and 0.22 ± 0.11 mM for inosine,l-homocysteine, andS-inosyl-l-homocysteine, respectively. No enzymatic activity was detected withS-adenosyl-l-homocysteine as the substrate in either the synthesis or hydrolysis direction. These results prompted us to redesignate theM. jannaschiienzyme anS-inosyl-l-homocysteine hydrolase (SIHH). Identification of SIHH demonstrates a modified pathway in this methanogen for the regeneration of SAM fromS-adenosyl-l-homocysteine that uses the deamination ofS-adenosyl-l-homocysteine to formS-inosyl-l-homocysteine.

IMPORTANCEIn strictly anaerobic methanogenic archaea, such asMethanocaldococcus jannaschii, canonical metabolic pathways are often not present, and instead, unique pathways that are deeply rooted on the phylogenetic tree are utilized by the organisms. Here, we discuss the recycling pathway forS-adenosyl-l-homocysteine, produced fromS-adenosyl-l-methionine (SAM)-dependent methylation reactions, which uses a hydrolase specific forS-inosyl-l-homocysteine, an uncommon metabolite. Identification of the pathways and the enzymes involved in the unique pathways in the methanogens will provide insight into the biochemical reactions that were occurring when life originated.
A Social Medium: ASM's 5th Cell-Cell Communication in Bacteria Meeting in Review
Authors: Gibbs Karine A. , Federle Michael J.
Published: April 2015

The 5th American Society for Microbiology Conference on Cell-Cell Communication in Bacteria (CCCB-5), which convened from 18 to 21 October 2014 in San Antonio, TX, highlighted recent advances in our understanding of microbial intercellular signaling. While the CCCB meetings arose from interests in pheromone signaling and quorum sensing, it was evident at CCCB-5 that the cell-cell communication field is continuing to mature, expanding into new areas and integrating cutting-edge technologies. In this minireview, we recap some of the research discussed at CCCB-5 and the questions that have arisen from it.
Escherichia coli YqjA, a Member of the Conserved DedA/Tvp38 Membrane Protein Family, Is a Putative Osmosensing Transporter Required for Growth at Alkaline pH
Authors: Kumar Sujeet , Doerrler William T.
Published: April 2015

The ability to persist and grow under alkaline conditions is an important characteristic of many bacteria. In order to survive at alkaline pH,
Escherichia coli
must maintain a stable cytoplasmic pH of about 7.6. Membrane cation/proton antiporters play a major role in alkaline pH homeostasis by catalyzing active inward proton transport. The DedA/Tvp38 family is a highly conserved membrane protein family of unknown function present in most sequenced genomes. YqjA and YghB are members of the
E. coli
DedA family with 62% amino acid identity and partially redundant functions. We have shown that
E. coli
with Δ
yqjA
and Δ
yghB
mutations cannot properly maintain the proton motive force (PMF) and is compromised in PMF-dependent drug efflux and other PMF-dependent functions. Furthermore, the functions of YqjA and YghB are dependent upon membrane-embedded acidic amino acids, a hallmark of several families of proton-dependent transporters. Here, we show that the Δ
yqjA
mutant (but not Δ
yghB
) cannot grow under alkaline conditions (ranging from pH 8.5 to 9.5), unlike the parent
E. coli
. Overexpression of
yqjA
restores growth at alkaline pH, but only when more than ∼100 mM sodium or potassium is present in the growth medium. Increasing the osmotic pressure by the addition of sucrose enhances the ability of YqjA to support growth under alkaline conditions in the presence of low salt concentrations, consistent with YqjA functioning as an osmosensor. We suggest that YqjA possesses proton-dependent transport activity that is stimulated by osmolarity and that it plays a significant role in the survival of
E. coli
at alkaline pH.

IMPORTANCE
The ability to survive under alkaline conditions is important for many species of bacteria.
Escherichia coli
can grow at pH 5.5 to 9.5 while maintaining a constant cytoplasmic pH of about 7.6. Under alkaline conditions, bacteria rely upon proton-dependent transporters to maintain a constant cytoplasmic pH. The DedA/Tvp38 protein family is a highly conserved but poorly characterized family of membrane proteins. Here, we show that the DedA/Tvp38 protein YqjA is critical for
E. coli
to survive at pH 8.5 to 9.5. YqjA requires sodium and potassium for this function. At low cation concentrations, osmolytes, including sucrose, can facilitate rescue of
E. coli
growth by YqjA at high pH. These data are consistent with YqjA functioning as an osmosensing cation-dependent proton transporter.