bluuebunny/crossref_metadata_2025 huggingface dataset:
In-Situ NDE Monitoring of Crack Bridging in Ceramic Composites via Crack Opening Displacement
Authors: Chulya Abhisak , Gyekenyesi John P.
Published: February 2015

A study of crack bridging in long-fiber reinforced ceramic matrix composites (CMC) is the main focus of this paper. The in-situ observation using NDE techniques reveals that 1D SiC/CAS CMCs show only partial fiber bridging behavior while 2D SiC/SiC CMCs possess an excellent bridging mechanism. Laser interferometric technique was successfully applied to measure crack opening displacements (COD) in the notched specimens under four-point flexural loading. The onset of precracking and the effects of fiber bridging were also detected by in-situ optical microscopy and acoustic emission techniques. The applied load-COD relations were shown and on the basis of these results, the bridging stiffness parameter can be determined via the fracture mechanics formulation proposed by Cox and Marshall.
Applications of Laser Systems to Cutting, Drilling and Welding Turbine Engine Parts
Authors: VanderWert Terry L.
Published: February 2015

Multi-axis laser materials processing systems are having a significant impact on the way turbine engine parts are being cut, drilled, and welded. The success of laser cutting, drilling and welding is based in the ability to concentrate laser energy into a small area and to produce features having narrow heat affected zones.

Reduced tooling expense, fast turnaround, and flexibility for handling design changes and for economical small lot manufacturing are some of the benefits associated with laser processing of turbine engine parts. For example, in replacing hand trimming, laser cutting has increased throughput for trimming a deep drawn gas turbine engine part from 18 pieces per day to 18 pieces in 30 minutes. For another company, laser cutting saved $75,000 in tooling expense for an application involving drilling of 3500, 0.33 mm diameter holes in a 0.36 mm thick turbine engine blade insert. Laser cutting and welding have been key to a major aircraft manufacturer’s implementation of Just-In-Time manufacturing practices.

Recent advances in design and control of laser processing systems have increased the number of applications for laser processing turbine engine parts. New processes have increased the range of applications for which laser processing is qualified. In-process gaging has been used to automate processes that were previously manual and, in doing so, increase the quality of the finished part and productivity of the manufacturing operation.

This paper reviews the laser processes used to cut, drill, and weld turbine engine parts. Some typical applications are presented to illustrate the benefits of laser systems for processing turbine engine parts.
The Effect of Reaction on Axial Flow Compressor Performance
Authors: Farmakalides C. D. , McKenzle A. B. , Elder R. L.
Published: February 2015

This paper describes a study of the effects of design-point reaction on axial flow compressor performance. Particular attention is given to differences in stable operating range and overall efficiency. Design of an 80% reaction, zero pre-whirl, blading is presented together with a discussion on the applicability of currently available design correlations, mostly derived from 50% reaction blading tests, to such high reaction blading. Experimental data obtained from tests carried out on a low speed 3-stage axial flow research facility, at Cranfield Institute of Technology (now Cranfield University), using an existing 50% reaction blading and the new 80% reaction blading indicate that high reaction designs can result in improved operating range at no loss of efficiency. Tests carried out include performance measurements for each of the two bladings at various stator stagger settings and include inter-row radial traversing at flow conditions near optimum and stall.
Evaluation of Ceramic Rotor Strength by Cold and Hot Spin Tests
Authors: Watanabe Makoto , Ogita Hiroshi
Published: February 2015

Presently in Japan 100 kW ceramic gas turbines (CGT) for automobiles are under development, parts of which include a turbine rotor, scrolls, a combustor, and other parts made of ceramics and ceramic matrix composites. The rotor is designed to rotate at 110,000 rpm, equal to the maximum stress of 300 MPa and to be exposed to temperatures up to 1350°C. Initially, the strength of ceramic rotors was evaluated by a burst test using a cold spin tester. The burst picture was observed and compared with the 4pt bending strength of the ceramic test specimens. Next, the strength of the rotors was tested by a hot spin test and the burst result of the rotor was evaluated.

A high speed camera was used to observe the rotor at the instant of burst under a high temperature condition.

Applying the result of the cold and hot spin tests, ceramics for turbine rotor were selected and the shape of the rotor was designed as a practical automotive engine began in 1990 as a project of the Petroleum Energy Center with financial support from the Agency of Natural Resources and Energy, the Ministry of International Trade and Industry. In order to obtain a 40% or higher thermal efficiency, the automotive gas turbine requires the use of a turbine rotor, combustor, shroud and other engine parts that can withstand high temperatures of 1200°C to 1500°C. In addition, since their resistance to thermal stress and impact are primary considerations, it is necessary to develop high heat-resistant materials (ceramic type materials). Fig. 1 shows a sectional model of the automotive ceramic gas turbine now under development. Under this project, a monolithic ceramic rotor was first evaluated as a turbine rotor. Ceramic matrix composites were then studied.
The Model V84.3 Shot Tests: Compressor Flow Field Measurements and Evaluation
Authors: Janssen M. , Mönig R. , Seume J. , Hönen H. , Lösch-Schloms R. , Gallus H. E.
Published: February 2015

Detailed experimental investigations were carried out at the Siemens test-facility in Berlin to validate and develop further the compressor design of the Model V84.3 gas turbine and to generate a comprehensive data base for the verification of the flow calculation programs. The test facility enables Siemens to confirm the design with regard to performance and reliability in the full scale machine under full load and off-design condition.

Various measuring techniques well established in the laboratory were applied to the full scale compressor to examine the flow field. Along with rather conventional 5-hole probes for measuring the flow field in the core region, miniaturized 3-hole probes were developed at the Turbomachinery Laboratory of the Technical University of Aachen, tested and finally used for the measurements of endwall boundary layer profiles and their development throughout the compressor. In addition to the probe measurements, wall static-pressure measurements, as well as probed vane measurements, were carried out.

The paper briefly describes the test facility, the compressor under investigation, and the instrumentation for the flow measurements. A comparison of the 3-hole and 5-hole probe measurements is presented. The experimental results are compared with calculated results taken from a two-dimensional off-design calculation program with standard loss models. By means of the measured static-pressure rise at the casing wall and the total pressure distributions downstream of the rotor rows, a modification of the loss modeling was performed. The calculated flow field is compared to the results of the 3-hole and 5-hole probe measurements in terms of radial distributions for flow angle. Mach number and total pressure.
A Fuel Oilpremix Burner for Gas Turbines: Development and Initial Operating Experience
Authors: Schetter Bernhard , Schabbehard Hans Wilhelm , Josefson Ulf , Ahlberg Anders
Published: February 2015

Premix combustion of natural gas in Siemens hybrid burners has been carried out successfully in gas turbine power plant since 1986 and has enabled NOx emissions below 10 ppm to be achieved without additional water or steam injection.

Based on this experience, the hybrid burner has been further developed for the premix combustion of fuel oil and is now in commercial operation in a Siemens Model V94.2 gas turbine at the Halmstad power plant in Sweden. The final testing of the new burners on site was carried out from January to September 1993 by courtesy of and in a fruitful cooperation with the client, SYDKRAFT AB.

This paper sets out a number of requirements for successful premix combustion of fuel oil, describes how these requirements have been met and concludes with the results of site measurements of NOx and CO emissions.

Base load NOx emissions were reduced to less than a quarter of their previous values without additional water or steam injection.
Multilevel Optimization Procedures for Gas Turbine Design: Part II — Solution and Examples
Authors: Ghiglino Fabio , Massardo Aristide
Published: February 2015

The mathematical formulations of two procedures for breaking down a large optimization energy problem into a hierarchy of separated but coupled subproblems were presented and discussed in the first part of this work (Ghiglino and Massardo, 1994). Here their applicability is illustrated by formulation of realistic analysis and design problems in the field of gas turbine systems, both for open and closed cycle plants. The definition of objective functions, design variables, constraints and subproblem analyses is discussed; the results obtained with the sensitivity, derivative procedure are compared with the results obtained with the linearization procedure.
CFD Modelling of an Advanced 1600 K Reverse-Flow Combustor
Authors: Martino P. Di , Colantuoni S. , Cirillo L. , Cinque G.
Published: February 2015

A fully-elliptic three dimensional computational fluid dynamic (CFD) code based on pressure-correction techniques has been used in the design of an advanced turbine single annular reverse-flow combustor (AR1600) under development at Alfa Romeo Avio (ARA).

Fuel injection was handled using a Lagrangian liquid droplet spray model coupled to the gas phase equations, which are solved in an Eulerian frame of reference. Turbulent transport is described by the standard k-ε model. The combustion model utilizes a conserved scalar formulation and an assumed shape probability density function to account for chemistry-turbulence interaction.

The numerical algorithm employs structured nonorthogonal curvilinear grids, node-centered variable arrangement and Cartesian velocity components.

The code was validated on a similar combustor (AR318 turboprop engine of 600 SHP). The numerical results agree well with the test measurements available for this chamber.

The aerothermal design of AR1600 (1600K exit temperature) has the same gemetrical constraints of AR318 (tip and root diameters for compressor outlet and turbine inlet), but the lenght is shorter to reduce surface area for less cooling and to utilize the excess air for more efficient mixing and combustion.
Uprated 501F Gas Turbine, 501FA
Authors: Aoki S. , Tsukuda Y. , Akita E. , Terazaki M. , McIaurin L. D. , Kizer M.
Published: February 2015

This paper introduces the engineering approach taken in developing the 501FA gas turbine, which is an uprated version of the existing 501F 150MW class gas turbine. The concepts and procedures which were utilized to uprate this gas turbine are also presented. To achieve better performance, new techniques were incorporated which reflected test results and operating experience. No advanced technologies were introduced. Instead, well experienced techniques are adopted so as not to deteriorate reliability. Improvement of the performance was mainly achieved mainly due to the reduction of cooling air. Tip clearances were also optimized based on shop test and field results.
A Study of the Unsteady Pressure of a Cascade Near Transonic Flow Condition
Authors: Atassi H. M. , Fang J. , Ferrand P.
Published: February 2015

The rise of the unsteady pressure magnitude along the surface of a cascade blade in unsteady transonic flow is examined. It is shown that a similar rise in the unsteady pressure may occur for high subsonic flows where the mean flow is near sonic condition. For a subsonic cascade this unsteady pressure bulge is found to be associated with the cut-on of a new acoustic mode in the upstream direction. The level of the pressure bulge is significantly reduced as a downstream propagating mode cuts on. It is therefore proposed that this phenomenon is the result of the blockage of upstream propagating acoustic waves by the transonic mean flow. A transonic convergent-divergent nozzle is used as a model for investigating the acoustic blockage effect. Analytical and numerical computations using unsteady nonlinear Euler equations are then carried out to analyze and quantify the upstream and dowstream propagation of acoustic disturbances in the nozzle. The results confirm the sharp rise in the pressure of the upstream propagating disturbances at the nozzle throat as a result of the acoustic blockage.
Casing Boundary Layer Control by Recess Vaned Casing for a Twin-Rotor Contra-Rotating Axial Flow Fan Unit
Authors: Roy Bhaskar , Agrawal Lokesh
Published: February 2015

In axial compressor or fan one of the major sources of losses is uncontrolled development of casing boundary layer and its interaction with the rotating blades. These losses are aggravated in an axial compressor or fan with low aspect ratio blades due to strong secondary flow development.

The recess vaned Casing treatment has been used in a low speed contra-rotating axial flow fan unit with low aspect ratio blades. The casing treatment aims at removing casing boundary layer from near the second fan tip and inject the flow back near the first fan tip. The treatment works on a principle of automatic suction and injection. The boundary layer control mechanism is expected to be automatically adjusted by axial static pressure gradient across the vanes.

The recess vaned casing treatment has yielded significant improvement in contra-rotating fan unit performance, and has increased the surge margin, essentially through fluid flow control near the casing.
Separated Flows in Axial Flow Compressor With Variable Stator Vanes at Positive Incidence Angles
Authors: Cyrus Vaclav
Published: February 2015

A detailed investigation of three-dimensional flow was carried out in a low speed rear axial compressor stage with the change of the stator blade row setting. The stator blade stagger change was in the range of (−14) – (23) degree. Measurements were performed by means of both stationary and rotating pressure probes at seven working points. The origin of large regions of separated flow in blade rows at positive incidence angles was analysed with the use of the spanwise diffusion factor distribution. These areas in the rotor and stator rows originated as the diffusion factor exceeded the critial value D = 0.6 within (1/4 – 1/3) of the blade height near one end-wall. The rotating stall in compressor stage arised when large regions of separated flow occured simultaneously in both rotor and stator blade rows.
The Performance of a Low Speed One and a Half Stage Axial Turbine With Varying Rotor Tip Clearance and Tip Gap Geometry
Authors: Morphis G. , Bindon J. P.
Published: February 2015

The performance of a low speed axial turbine followed by a second stage nozzle is measured with particular reference to the understanding of tip clearance effects in a real machine and to possible benefits of streamlined low loss rotor tips.

A radiused pressure edge was found to improve the performance of b single stage and of a one and a half stage turbine at the small tip clearance levels for which the radius was selected. This is in contrast to cascade results where mixing loss reduced the benefits of such tips. Clearance gap flow appears therefore to be just like other turbine flow where the loss mechanism of separation must be avoided. Loss formation within and downstream of a rotor are more complex than previously realized and do not obey the simple rules that have been used to design for minimum tip clearance loss. For example, approximately 48% of the tip leakage mass flow within a rotor appears to be a flat wall jet rather than a wrapped up vortex.

The second stage nozzle efficiency was found to be significantly higher than for the first stage and to even increase with tip clearance. This is a surprising result since it means that not only is there a reduction in secondary flow loss but also that rotor leakage and rotor secondary flows do not generate downstream mixing loss.
SPSLIFE: A User Friendly Approach to the Structural Design and Life Assessment of Ceramic Components
Authors: Bornemisza Tibor , Saith Arun
Published: February 2015

In order to expedite the structural analysis of ceramic components Sundstrand Power Systems has developed a proprietary computer code called “SPSLIFE”, which can substantially reduce the time spent on the design assessment of ceramic components. The life assessment computations for the various failure modes are performed using the structural analysis and materials files as input data. A number of “menus” are incorporated to request user input data and to guide the user through the problem definition process. The user has the capability to select existing material data files or create new ones. The computational modules are based on the analytical approaches currently used in the industry. The modular construction of the code facilitates making revisions or adding new modules. Graphic display is used to provide a visual summary of the life assessment calculations for the various failure modes. The output files generated provide a detailed review of the results which is helpful for design optimization. Independently derived component fast fracture and static fatigue survival probabilities using the NASA CARES and CARES/LIFE codes are displayed for reference. The paper provides an application example using a patented design of a ceramic monorotor for the Sundstrand Power Systems TJ-50 small gas turbine engine.
Comparison of NDE Results and Correlation With Microstructural Characteristics of NiFeAl/Wf
Authors: Hsu David K. , Liaw Peter K. , Baaklini George Y.
Published: February 2015

Metal matrix composites (MMC) and intermetallic matrix composites (IMC) are materials of complex structure. Nominally defect-free, as-manufactured MMC requires nondestructive evaluation (NDE) for quality assurance and process monitoring purposes. In this work, three NDE techniques — ultrasonics, eddy current, and X-ray radiography — were applied to un-damaged NiFeAI/Wf coupons. Images of the coupons were obtained using the three techniques. The NDE results were compared among themselves, and correlations were sought between these results and microstructural features of the specimen. Consistencies were found among the NDE results and a strong correlation was found between the spatial variation of fiber density and the NDE signals.
Aspects of Flame Stability in a Research Dump Combustor
Authors: Sturgess G. J. , Hedman P. O. , Sloan D. G. , Shouse D.
Published: February 2015

The lean blowout process is studied in a simplified, nominally diffusion flame research combustor that incorporates the essential features of the combustor primary zone for an aircraft gas turbine engine. The research combustor is provided with extensive optical access. To investigate the blowout, a variety of diagnostic techniques are employed, including direct flame observation, laser-Doppler anemometry, spontaneous OH-imaging, thin-filament pyrometry, laser-induced fluorescence OH-imaging, coherent anti-Stokes Raman spectroscopy, and computational fluid dynamics. Lean blowouts in the research combustor are related to well-stirred reactor blowout. A blowout sequence is found to initiated by the loss of a key flame structure in the form of an attached pilot flame. The behavior of this attached flame is investigated. It is concluded that a major contribution to the existence of the attached flame is near-field, non-stationary radial transport of reactants directly into the recirculation zone, rather than by mean flow recirculation of hot products. “Lift” of the attached flame is the reason that lean blowout in the research combustor is related to well-stirred reactor blowout since it allows at least partial premixing of reactants to take place.
Gas Turbine Units for Pipeline Compressor Stations: Environmental Update Problems
Authors: Sudarev A. V. , Zakharov Y. I. , Vinogradov E. D. , Vesely S. , Poslushny G.
Published: February 2015

The exhaust of nitrogen oxides into atmosphere is the most stringent environmental challenge in the operation of gas pipeline gas turbine plants. In 1991–1993 NITI EM along with EKOL retrofitted over 170 GTK-10 and GT-750-6 type gas turbine combustors of the “Tyumentransgas” and “Transit” (Czech Republic) gas transmission enterprises. Operations were carried out directly at the gas pumping stations.

Emissions of the retrofitted units are within a range of 135–175 mg/Nm3 of oxides of nitrogen (NOx) referred to 15% O2 and carbon monoxide (CO) content of the exhaust gases does not exceed 100 mg/Nm3, at 15% O2.
Photoelectron spectra of finite-thickness layers
Authors: Afanas'ev Viktor P. , Golovina Olga Y. , Gryazev Alexander S. , Efremenko Dmitry S. , Kaplya Pavel S.
Published: February 2015

A method of computing x-ray photoemission spectra in the wide range of energy losses and different sighting angles is presented. Photoemission spectra for layers of finite thickness are investigated. Angular and energy spectra are analyzed using the invariant imbedding principle. They are computed using small-angle approximation and the exact numerical solution of the multiple photoelectron scattering events in solids. The presented methods of x-ray photoemission spectra analysis are compared regarding their efficiencies. Comparison of the exact numerical solution to those based on straight line approximation and small-angle approximation reveals an error in straight line approximation of about 50%. Numerical solutions are compared with the experimental data and Monte-Carlo simulations.
Image quality dependency on system configuration and tube voltage in chest tomosynthesis—A visual grading study using an anthropomorphic chest phantom
Authors: Söderman Christina , Asplund Sara , Allansdotter Johnsson Åse , Vikgren Jenny , Rossi Norrlund Rauni , Molnar David , Svalkvist Angelica , Gunnar Månsson Lars , Båth Magnus
Published: February 2015

Purpose:

To investigate the potential benefit of increasing the dose per projection image in chest tomosynthesis, performed at the current standard dose level, by reducing the angular range covered or the projection image density and to evaluate the influence of the tube voltage on the image quality.

Methods:

An anthropomorphic chest phantom was imaged using nine different projection image configurations and ten different tube voltages with the GE VolumeRAD tomosynthesis system. The resulting image sets were representative of being acquired at the same total effective dose. This was achieved partly by applying a simulated dose reduction to the projection images due to restrictions concerning the tube load settings on the VolumeRAD system. Four observers were included in a visual grading study where the reconstructed tomosynthesis section images were rated according to a set of image quality criteria. Image quality was evaluated relative to the default configuration and default tube voltage on the VolumeRAD system.

Results:

Overall, the image quality decreased with decreasing projection image density. Regarding angular range covered by the projection images, the image quality increased with decreasing angular range for two of the criteria, whereas for a criterion related to the depth resolution in the section images the reduced angular ranges resulted in inferior image quality as compared to the default configuration. The image quality showed little dependence on the tube voltage.

Conclusions:

At the standard dose level of the VolumeRAD system, the potential benefits from increasing the dose per projection do not fully compensate for the negative effects resulting from a reduction in the number of projection images. Consequently, the default configuration consisting of 60 projection images acquired over 30° is a good alternative. The tube voltage used in tomosynthesis does not have a large impact on the image quality.
How Much Does a Half-Kilogram of Water “Weigh”?
Authors: Koumaras Panagiotis , Pierratos Theodoros
Published: February 2015

Many educators have utilized the phenomenon of the so-called “hydrostatic paradox” to actively engage students in classroom instructional activities related to hydrostatic equilibrium.1 Various approaches requiring different levels of mathematical knowledge have been proposed in the literature to provide students clear explanations of this paradox.2 However, these attempts take for granted that students have already been taught and have internalized the concepts of force and pressure. The hydrostatic paradox is then usually introduced as an application problem for the evaluation of the knowledge acquired.
The dipolar express: An electromagnetically driven train
Authors: Irons Stephen
Published: February 2015

Recently an eye-catching YouTube video captivated the attention of many members of the TAP-L (Teaching AP-paratus Listserve, http://demoroom.physics.ncsu.edu/tapl/) community. It shows a AA battery with magnets affixed to each end, racing around the inside of a coil of wire (Fig. 1). The cleverness and simplicity of the demonstration was apparent to all. With no internal moving parts, it is not immediately obvious what makes it energetically zip through the coil, but you really want to know.
Stimulus ratio dependence of low-frequency distortion-product otoacoustic emissions in humans
Authors: Christensen Anders T. , Ordoñez Rodrigo , Hammershøi Dorte
Published: February 2015

Active amplifiers within the cochlea generate, as a by-product of their function, distortion-product otoacoustic emissions (DPOAEs) in response to specific two-tone stimuli. Focus has been on invoking emissions in a mid-frequency range from ∼0.5 to 4 kHz. The present study investigates stimulus parameters of the DPOAE at 2f1−f2 frequencies below 0.5 kHz. Eighteen out of 21 young human adults screened had audiometrically normal hearing for inclusion in the experiment. DPOAEs were measured with pure-tone stimuli in four configurations: f2 fixed around 2.13 kHz, f2 fixed around 0.53 kHz, 2f1−f2 fixed at 1.23 kHz and 0.25 kHz. Eight stimulus ratios, f2/f1, and three stimulus sound pressure levels, L1/L2, were measured in each configuration. Trends in ratio-magnitude responses for the mid-frequency DPOAE agree with those reported in previous literature. DPOAEs are not limited to distortion frequencies >0.5 kHz, but the stimulus ratio invoking the largest DPOAE in the mid-frequency range does not do so in the low-frequency range. Guiding the ratio according to the equivalent rectangular bandwidth of auditory filters maintains the DPOAE level.
Frequency and amplitude estimation of the first peak of head-related transfer functions from individual pinna anthropometry
Authors: Mokhtari Parham , Takemoto Hironori , Nishimura Ryouichi , Kato Hiroaki
Published: February 2015

The first (lowest) peak of head-related transfer functions (HRTFs) is known to be a concha depth resonance and a spectral cue in human sound localization. However, there is still no established model to estimate its center-frequency F1 and amplitude A1 from pinna anthropometry. Here, with geometries of 38 pinnae measured and their median-plane HRTFs calculated by numerical simulation, linear regression models were evaluated in estimating F1 and A1 from 25 concha depth and aperture measurements. F1 was best estimated (correlation coefficient r = 0.84, mean absolute error MAE = 118 Hz) by lateral distances from the base of the posterior cavum concha to the outer surface of the antitragus and antihelix (longest measures of concha depth). A1 was best estimated (r = 0.83, MAE = 0.84 dB) by the lateral distance from the ear-canal entrance to the side of the cheek near the anterior notch (shortest measure of concha depth) and by the equivalent diameter of the concha aperture. These results suggest that the first resonance's quarter-wavelength corresponds to the longest lateral extent of the concha and that its energy lost to the surrounding air depends on the concha aperture and the cavum concha's shortest lateral depth.
A convolution model for computing the far-field directivity of a parametric loudspeaker array
Authors: Shi Chuang , Kajikawa Yoshinobu
Published: February 2015

This paper describes a method to compute the far-field directivity of a parametric loudspeaker array (PLA), whereby the steerable parametric loudspeaker can be implemented when phased array techniques are applied. The convolution of the product directivity and the Westervelt's directivity is suggested, substituting for the past practice of using the product directivity only. Computed directivity of a PLA using the proposed convolution model achieves significant improvement in agreement to measured directivity at a negligible computational cost.
Effects of higher order propagation modes in vocal tract like geometries
Authors: Blandin Rémi , Arnela Marc , Laboissière Rafael , Pelorson Xavier , Guasch Oriol , Hirtum Annemie Van , Laval Xavier
Published: February 2015

In this paper, a multimodal theory accounting for higher order acoustical propagation modes is presented as an extension to the classical plane wave theory. This theoretical development is validated against experiments on vocal tract replicas, obtained using a 3D printer and finite element simulations. Simplified vocal tract geometries of increasing complexity are used to investigate the influence of some geometrical parameters on the acoustical properties of the vocal tract. It is shown that the higher order modes can produce additional resonances and anti-resonances and can also strongly affect the radiated sound. These effects appear to be dependent on the eccentricity and the cross-sectional shape of the geometries. Finally, the comparison between the simulations and the experiments points out the importance of taking visco-thermal losses into account to increase the accuracy of the resonance bandwidths prediction.
Infrasonic ray tracing applied to small-scale atmospheric structures: Thermal plumes and updrafts/downdrafts
Authors: Jones R. Michael , Bedard Alfred J.
Published: February 2015

A ray-tracing program is used to estimate the refraction of infrasound by the vertical structure of the atmosphere in thermal plumes, showing only weak effects, as well as in updrafts and downdrafts, which can act as vertical wave guides. Thermal plumes are ubiquitous features of the daytime atmospheric boundary layer. The effects of thermal plumes on lower frequency sound propagation are minor with the exception of major events, such as volcanoes, forest fires, or industrial explosions where quite strong temperature gradients are involved. On the other hand, when strong, organized vertical flows occur (e.g., in mature thunderstorms and microbursts), there are significant effects. For example, a downdraft surrounded by an updraft focuses sound as it travels upward, and defocuses sound as it travels downward. Such propagation asymmetry may help explain observations that balloonists can hear people on the ground; but conversely, people on the ground cannot hear balloonists aloft. These results are pertinent for those making surface measurements from acoustic sources aloft, as well as for measurements of surface sound sources using elevated receivers.
Analysis of tissue changes, measurement system effects, and motion artifacts in echo decorrelation imaging
Authors: Hooi Fong Ming , Nagle Anna , Subramanian Swetha , Douglas Mast T.
Published: February 2015

Echo decorrelation imaging, a method for mapping ablation-induced ultrasound echo changes, is analyzed. Local echo decorrelation is shown to approximate the decoherence spectrum of tissue reflectivity. Effects of the ultrasound measurement system, echo signal windowing, electronic noise, and tissue motion on echo decorrelation images are determined theoretically, leading to a method for reduction of motion and noise artifacts. Theoretical analysis is validated by simulations and experiments. Simulated decoherence of the scattering medium was recovered with root-mean-square error less than 10% with accuracy dependent on the correlation window size. Motion-induced decorrelation measured in an ex vivo pubovisceral muscle model showed similar trends to theoretical motion-induced decorrelation for a 2.1 MHz curvilinear array with decorrelation approaching unity for 3–4 mm elevational displacement or 1–1.6 mm range displacement. For in vivo imaging of porcine liver by a 7 MHz linear array, theoretical decorrelation computed using image-based motion estimates correlated significantly with measured decorrelation (r = 0.931, N = 10). Echo decorrelation artifacts incurred during in vivo radiofrequency ablation in the same porcine liver were effectively compensated based on the theoretical echo decorrelation model and measured pre-treatment decorrelation. These results demonstrate the potential of echo decorrelation imaging for quantification of heat-induced changes to the scattering tissue medium during thermal ablation.
Antileishmanial Effect of 18β-Glycyrrhetinic Acid Is Mediated by Toll-Like Receptor-Dependent Canonical and Noncanonical p38 Activation
Authors: Gupta Purnima , Das Pijush K. , Ukil Anindita
Published: February 2015

18β-Glycyrrhetinic acid (GRA), a natural immunomodulator, greatly reduced the parasite load in experimental visceral leishmaniasis through nitric oxide (NO) upregulation, proinflammatory cytokine expression, and NF-κB activation. For the GRA-mediated effect, the primary kinase responsible was found to be p38, and analysis of phosphorylation kinetics as well as studies with dominant-negative (DN) constructs revealed mitogen-activated protein kinase kinase 3 (MKK3) and MKK6 as the immediate upstream regulators of p38. However, detection of remnant p38 kinase activity in the presence of both DN MKK3 and MKK6 suggested alternative pathways of p38 activation. That residual p38 activity was attributed to an autophosphorylation event ensured by the transforming growth factor β-activated kinase 1 (TAK1)-binding protein 1 (TAB1)-p38 interaction and was completely abolished upon pretreatment with SB203580 in DN MKK3/6 double-transfected macrophage cells. Further upstream signaling evaluation by way of phosphorylation kinetics and transfection studies with DN constructs identified TAK1, myeloid differentiation factor 88 (MyD88), interleukin 1 receptor (IL-1R)-activated kinase 1 (IRAK1), and tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) as important contributors to GRA-mediated macrophage activation. Finally, gene knockdown studies revealed Toll-like receptor 2 (TLR2) and TLR4 as the membrane receptors associated with GRA-mediated antileishmanial activity. Together, the results of this study brought mechanistic insight into the antileishmanial activity of GRA, which is dependent on the TLR2/4-MyD88 signaling axis, leading to MKK3/6-mediated canonical and TAB1-mediated noncanonical p38 activation.
The Mu Subunit of Plasmodium falciparum Clathrin-Associated Adaptor Protein 2 Modulates
In Vitro
Parasite Response to Artemisinin and Quinine
Authors: Henriques Gisela , van Schalkwyk Donelly A. , Burrow Rebekah , Warhurst David C. , Thompson Eloise , Baker David A. , Fidock David A. , Hallett Rachel , Flueck Christian , Sutherland Colin J.
Published: February 2015

The emergence of drug-resistant parasites is a serious threat faced by malaria control programs. Understanding the genetic basis of resistance is critical to the success of treatment and intervention strategies. A novel locus associated with antimalarial resistance,
ap2-mu
(encoding the mu chain of the adaptor protein 2 [AP2] complex), was recently identified in studies on the rodent malaria parasite
Plasmodium chabaudi
(
pcap2-mu
). Furthermore, analysis in Kenyan malaria patients of polymorphisms in the
Plasmodium falciparum
ap2-mu
homologue,
pfap2-mu
, found evidence that differences in the amino acid encoded by codon 160 are associated with enhanced parasite survival
in vivo
following combination treatments which included artemisinin derivatives. Here, we characterize the role of
pfap2-mu
in mediating the
in vitro
antimalarial drug response of
P. falciparum
by generating transgenic parasites constitutively expressing codon 160 encoding either the wild-type Ser (Ser160) or the Asn mutant (160Asn) form of
pfap2-mu
. Transgenic parasites carrying the
pfap2-mu
160Asn allele were significantly less sensitive to dihydroartemisinin using a standard 48-h
in vitro
test, providing direct evidence of an altered parasite response to artemisinin. Our data also provide evidence that
pfap2-mu
variants can modulate parasite sensitivity to quinine. No evidence was found that
pfap2-mu
variants contribute to the slow-clearance phenotype exhibited by
P. falciparum
in Cambodian patients treated with artesunate monotherapy. These findings provide compelling evidence that
pfap2-mu
can modulate
P. falciparum
responses to multiple drugs. We propose that this gene should be evaluated further as a potential molecular marker of antimalarial resistance.
Eravacycline (TP-434) Is Efficacious in Animal Models of Infection
Authors: Grossman Trudy H. , Murphy Timothy M. , Slee Andrew M. , Lofland Denene , Sutcliffe Joyce A.
Published: February 2015

Eravacycline is a novel broad-spectrum fluorocycline antibiotic being developed for a wide range of serious infections. Eravacycline was efficacious in mouse septicemia models, demonstrating 50% protective dose (PD
50
) values of ≤1 mg/kg of body weight once a day (q.d.) against
Staphylococcus aureus
, including tetracycline-resistant isolates of methicillin-resistant
S. aureus
(MRSA), and
Streptococcus pyogenes
. The PD
50
values against
Escherichia coli
isolates were 1.2 to 4.4 mg/kg q.d. In neutropenic mouse thigh infection models with methicillin-sensitive
S. aureus
(MSSA) and
S. pyogenes
, eravacycline produced 2 log
10
reductions in CFU at single intravenous (i.v.) doses ranging from 0.2 to 9.5 mg/kg. In a neutropenic mouse lung infection model, eravacycline administered i.v. at 10 mg/kg twice a day (b.i.d.) reduced the level of tetracycline-resistant MRSA in the lung equivalent to that of linezolid given orally (p.o.) at 30 mg/kg b.i.d. At i.v. doses of 3 to 12 mg/kg b.i.d., eravacycline was more efficacious against tetracycline-resistant
Streptococcus pneumoniae
in a neutropenic lung infection model than linezolid p.o. at 30 mg/kg b.i.d. Eravacycline showed good efficacy at 2 to 10 mg/kg i.v. b.i.d., producing up to a 4.6 log
10
CFU reduction in kidney bacterial burden in a model challenged with a uropathogenic
E. coli
isolate. Eravacycline was active in multiple murine models of infection against clinically important Gram-positive and Gram-negative pathogens.
Avibactam and Inhibitor-Resistant SHV β-Lactamases
Authors: Winkler Marisa L. , Papp-Wallace Krisztina M. , Taracila Magdalena A. , Bonomo Robert A.
Published: February 2015

β-Lactamase enzymes (EC 3.5.2.6) are a significant threat to the continued use of β-lactam antibiotics to treat infections. A novel non-β-lactam β-lactamase inhibitor with activity against many class A and C and some class D β-lactamase variants, avibactam, is now available in the clinic in partnership with ceftazidime. Here, we explored the activity of avibactam against a variety of characterized isogenic laboratory constructs of β-lactamase inhibitor-resistant variants of the class A enzyme SHV (M69I/L/V, S130G, K234R, R244S, and N276D). We discovered that the S130G variant of SHV-1 shows the most significant resistance to inhibition by avibactam, based on both microbiological and biochemical characterizations. Using a constant concentration of 4 mg/liter of avibactam as a β-lactamase inhibitor in combination with ampicillin, the MIC increased from 1 mg/liter for
bla
SHV-1
to 256 mg/liter for
bla
SHV S130G
expressed in
Escherichia coli
DH10B. At steady state, the
k
2
/
K
value of the S130G variant when inactivated by avibactam was 1.3 M
−1
s
−1
, versus 60,300 M
−1
s
−1
for the SHV-1 β-lactamase. Under timed inactivation conditions, we found that an approximately 1,700-fold-higher avibactam concentration was required to inhibit SHV S130G than the concentration that inhibited SHV-1. Molecular modeling suggested that the positioning of amino acids in the active site of SHV may result in an alternative pathway of inactivation when complexed with avibactam, compared to the structure of CTX-M-15–avibactam, and that S130 plays a role in the acylation of avibactam as a general acid/base. In addition, S130 may play a role in recyclization. As a result, we advance that the lack of a hydroxyl group at position 130 in the S130G variant of SHV-1 substantially slows carbamylation of the β-lactamase by avibactam by (i) removing an important proton acceptor and donator in catalysis and (ii) decreasing the number of H bonds. In addition, recyclization is most likely also slow due to the lack of a general base to initiate the process. Considering other inhibitor-resistant mechanisms among class A β-lactamases, S130 may be the most important amino acid for the inhibition of class A β-lactamases, perhaps even for the novel diazabicyclooctane class of β-lactamase inhibitors.
A Novel Tricyclic Ligand-Containing Nonpeptidic HIV-1 Protease Inhibitor, GRL-0739, Effectively Inhibits the Replication of Multidrug-Resistant HIV-1 Variants and Has a Desirable Central Nervous System Penetration Property
In Vitro
Authors: Amano Masayuki , Tojo Yasushi , Salcedo-Gómez Pedro Miguel , Parham Garth L. , Nyalapatla Prasanth R. , Das Debananda , Ghosh Arun K. , Mitsuya Hiroaki
Published: February 2015

We report here that GRL-0739, a novel nonpeptidic HIV-1 protease inhibitor containing a tricycle (cyclohexyl-
bis
-tetrahydrofuranylurethane [THF]) and a sulfonamide isostere, is highly active against laboratory HIV-1 strains and primary clinical isolates (50% effective concentration [EC
50
], 0.0019 to 0.0036 μM), with minimal cytotoxicity (50% cytotoxic concentration [CC
50
], 21.0 μM). GRL-0739 blocked the infectivity and replication of HIV-1
NL4-3
variants selected by concentrations of up to 5 μM ritonavir or atazanavir (EC
50
, 0.035 to 0.058 μM). GRL-0739 was also highly active against multidrug-resistant clinical HIV-1 variants isolated from patients who no longer responded to existing antiviral regimens after long-term antiretroviral therapy, as well as against the HIV-2
ROD
variant. The development of resistance against GRL-0739 was substantially delayed compared to that of amprenavir (APV). The effects of the nonspecific binding of human serum proteins on the anti-HIV-1 activity of GRL-0739 were insignificant. In addition, GRL-0739 showed a desirable central nervous system (CNS) penetration property, as assessed using a novel
in vitro
blood-brain barrier model. Molecular modeling demonstrated that the tricyclic ring and methoxybenzene of GRL-0739 have a larger surface and make greater van der Waals contacts with protease than in the case of darunavir. The present data demonstrate that GRL-0739 has desirable features as a compound with good CNS-penetrating capability for treating patients infected with wild-type and/or multidrug-resistant HIV-1 variants and that the newly generated cyclohexyl-
bis
-THF moiety with methoxybenzene confers highly desirable anti-HIV-1 potency in the design of novel protease inhibitors with greater CNS penetration profiles.
Characterization of a Large Cluster of Influenza A(H1N1)pdm09 Viruses Cross-Resistant to Oseltamivir and Peramivir during the 2013-2014 Influenza Season in Japan
Authors: Takashita Emi , Kiso Maki , Fujisaki Seiichiro , Yokoyama Masaru , Nakamura Kazuya , Shirakura Masayuki , Sato Hironori , Odagiri Takato , Kawaoka Yoshihiro , Tashiro Masato
Published: February 2015

Between September 2013 and July 2014, 2,482 influenza 2009 pandemic A(H1N1) [A(H1N1)pdm09] viruses were screened in Japan for the H275Y substitution in their neuraminidase (NA) protein, which confers cross-resistance to oseltamivir and peramivir. We found that a large cluster of the H275Y mutant virus was present prior to the main influenza season in Sapporo
/
Hokkaido, with the detection rate for this mutant virus reaching 29% in this area. Phylogenetic analysis suggested the clonal expansion of a single mutant virus in Sapporo
/
Hokkaido. To understand the reason for this large cluster, we examined the
in vitro
and
in vivo
properties of the mutant virus. We found that it grew well in cell culture, with growth comparable to that of the wild-type virus. The cluster virus also replicated well in the upper respiratory tract of ferrets and was transmitted efficiently between ferrets by way of respiratory droplets. Almost all recently circulating A(H1N1)pdm09 viruses, including the cluster virus, possessed two substitutions in NA, V241I and N369K, which are known to increase replication and transmission fitness. A structural analysis of NA predicted that a third substitution (N386K) in the NA of the cluster virus destabilized the mutant NA structure in the presence of the V241I and N369K substitutions. Our results suggest that the cluster virus retained viral fitness to spread among humans and, accordingly, caused the large cluster in Sapporo/Hokkaido. However, the mutant NA structure was less stable than that of the wild-type virus. Therefore, once the wild-type virus began to circulate in the community, the mutant virus could not compete and faded out.
Amplification of
pfmdr1
,
pfcrt
,
pvmdr1
, and K13 Propeller Polymorphisms Associated with Plasmodium falciparum and Plasmodium vivax Isolates from the China-Myanmar Border
Authors: Feng Jun , Zhou Daili , Lin Yingxue , Xiao Huihui , Yan He , Xia Zhigui
Published: February 2015

Malaria in the China-Myanmar border region is still severe; local transmission of both falciparum and vivax malaria persists, and there is a risk of geographically expanding antimalarial resistance. In this research, the
pfmdr1
,
pfcrt
,
pvmdr1
, and K13-propeller genotypes were determined in 26
Plasmodium falciparum
and 64
Plasmodium vivax
isolates from Yingjiang county of Yunnan province. The
pfmdr1
(11.5%),
pfcrt
(34.6%), and
pvmdr1
(3.1%) mutations were prevalent at the China-Myanmar border. The indigenous samples exhibited prevalences of 14.3%, 28.6%, and 14.3% for
pfmdr1
N86Y,
pfcrt
K76T, and
pfcrt
M74I, respectively, whereas the samples from Myanmar showed prevalences of 10.5%, 21.1%, and 5.3%, respectively. The most prevalent genotypes of
pfmdr1
and
pfcrt
were Y
86
Y
184
and M
74
N
75
T
76
, respectively. No
pvmdr1
mutation occurred in the indigenous samples but was observed in two cases coming from Myanmar. In addition, we are the first to report on 10 patients (38.5%) with five different K13 point mutations. The F446I allele is predominant (19.2%), and its prevalence was 28.6% in the indigenous samples of Yingjiang county and 15.8% in samples from Myanmar. The present data might be helpful for enrichment of the molecular surveillance of antimalarial resistance and useful for developing and updating guidance for the use of antimalarials in this region.