bluuebunny/crossref_metadata_2025 huggingface dataset:
Experimental Investigation of Stall and Surge in a Multistage Compressor
Authors: Munari Enrico , Morini Mirko , Pinelli Michele , Spina Pier Ruggero , Suman Alessio
Published: September 2016

Flow instability conditions, in particular during surge and stall phenomena, have always influenced the operational reliability of turbo-compressors and have attracted significant interest resulting in extensive literature. Nowadays, this subject is still one of the most investigated because of its high relevance on centrifugal and axial compressor operating flow range, performance and efficiency. Many researchers approach this important issue by developing numerical models, whereas others approach it through experimental studies specifically carried out in order to better comprehend this phenomenon. The aim of this paper is to experimentally analyze the stable and unstable operating conditions of an aeronautic turbo-shaft gas turbine axial-centrifugal compressor installed on a brand new test-rig properly designed for this purpose.

The test facility is set up in order to obtain i) the compressor performance maps at rotational speeds up to 25,000 rpm and ii) the compressor transient behavior during surge. By using two different test rig layouts, instabilities occurring in the compressor, beyond the peak of the characteristic curve, are identified and investigated.

These two types of analysis are carried out thanks to pressure, temperature and mass flow sensors located in strategic positions along the circuit. These measurement sensors are part of a proper control and acquisition system, characterized by an adjustable sampling frequency. Thus, the desired operating conditions of the compressor, in terms of mass flow and rotational speed and transient of these two parameters are regulated by this dedicated control system.
The Low Reduced Frequency Limit of Vibrating Airfoils: Part IIIA — Theoretical Quantification and Influence of Unsteady Loading
Authors: Corral Roque , Vega Almudena
Published: September 2016

This paper studies the unsteady aerodynamics of vibrating airfoils in the low reduced frequency regime with special emphasis on its impact on the work per cycle curves. In Part I of the corresponding paper, a perturbation analysis of the linearized Navier-Stokes equations for real modes at low reduced frequency was presented and some conclusions were drawn. It was discovered that a new parameter, the unsteady loading, plays an essential role in the trends of the phase and modulus of the unsteady pressure caused by the oscillation of the airfoil. In this third (a) part, the theory is extended in order to quantify the new parameter. It is shown that this parameter depends solely on the steady flowfield on the airfoil surface and the vibration mode-shape. As a consequence, the effect of changing the design operating conditions or the vibration mode onto the work-per-cycle curves (and therefore in the stability) can be easily predicted and, what is more important, quantified without conducting additional flutter analysis. The relevance of the parameter has been numerically confirmed in the Part IIIb of the paper.
Comparison of Two Numerical Algorithms for Computing the Effects of Mistuning of Fan Flutter
Authors: Salles L. , Vahdati M.
Published: September 2016

The aim of this paper is to study the effects of mistuning on fan flutter and to compare the prediction of two numerical models of different fidelity. The high fidelity model used here is a three-dimensional, whole assembly, time-accurate, viscous, finite-volume compressible flow solver. The Code used for this purpose is AU3D, written in Imperial College and validated for flutter computations over many years. To the best knowledge of authors, this is the first time such computations have been attempted. This is due to the fact that, such non-linear aeroelastic computations with mistuning require large amount of CPU time and cannot be performed routinely and consequently, faster (low fidelity) models are required for this task. Therefore, the second model used here is the aeroelastic fundamental mistuning model (FMM) and it based on an eigenvalue analysis of the linearized modal aeroelastic system with the aerodynamic matrix calculated from the aerodynamic influence coefficients. The influence coefficients required for this algorithm are obtained from the time domain non-linear Code by shaking one blade in the datum (tuned) frequency and mode. Once the influence coefficients have been obtained, the computations of aero damping require minimal amount of CPU time and many different mistuning patterns can be studied. The objectives of this work are to:

1. Compare the results between the two models and establish the capabilities/limitations of aeroelastic FMM,

2. Check if the introduction of mistuning would bring the experimental and computed flutter boundaries closer,

3. Establish a relationship between mistuning and damping.

A rig wide-chord fan blade, typical of modern civil designs, was used as the benchmark geometry for this study. All the flutter analyses carried out in this paper are with frequency mistuning, but the possible consequences of mistuned mode shapes are briefly discussed at the end of this paper. Only the first family of modes (1F, first flap) is considered in this work. For the frequency mistuning analysis, the 1F frequency is varied around the annulus but the 1F mode shapes remain the same for all the blades. For the mode shape mistuning computations, an FE analysis of the whole assembly different mass blades is performed.

The results of this work clearly show the importance of mistuning on flutter. It also demonstrates that when using rig test data for aeroelastic validation of CFD codes, the amount mistuning present must be known.

Finally, it should be noted that the aim of this paper is the study of mistuning and not steady/unsteady validation of a CFD code and therefore minimal aerodynamic data are presented.
Numerical Investigation of Boundary Layers in Wet Steam Nozzles
Authors: Starzmann Jörg , Hughes Fiona R. , White Alexander J. , Grübel Marius , Vogt Damian M.
Published: September 2016

Condensing nozzle flows have been used extensively to validate wet steam models. Many test cases are available in the literature and in the past a range of numerical studies have dealt with this challenging task. It is usually assumed that the nozzles provide a one- or two-dimensional flow with a fully turbulent boundary layer. The present paper reviews these assumptions and investigates numerically the influence of boundary layers on dry and wet steam nozzle expansions.

For the narrow nozzle of Moses and Stein it is shown that the pressure distribution is significantly affected by the additional blockage due to the side wall boundary layer. Comparison of laminar and turbulent flow predictions for this nozzles suggests that laminar-turbulent transition only occurs after the throat. Other examples are the Binnie nozzle and the Moore nozzles for which it is known that sudden changes in wall curvature produce expansion and compression waves that interact with the boundary layers. The differences between two- and three-dimensional calculations for these cases and the influence of laminar and turbulent boundary layers are discussed.

The present results reveal that boundary layer effects can have a considerable impact on the mean nozzle flow and thus on the validation process of condensation models. In order to verify the accuracy of turbulence modelling a test case that is not widely known internationally is included within the present study. This experimental work is remarkable because it includes boundary layer data as well as the usual pressure measurements along the nozzle centreline. Predicted and measured boundary layer profiles are compared and the effect of different turbulence models is discussed. Most of the numerical results are obtained with the in-house wet steam RANS-solver, Steamblock, but for the purpose of comparison the commercial program ANSYS CFX is also used, providing a wider range of standard RANS-based turbulence models.
Experimental Investigation on Swirl and Heat Transfer Within a Rotor-Stator Cavity
Authors: Massini Daniele , Facchini Bruno , Micio Mirko , Da Soghe Riccardo
Published: September 2016

A rotating test rig, reproducing a rotor-stator cavity with an axial admission system, has been exploited for an experimental investigation on the internal flow field and its effect on heat transfer on the stator side.

Working conditions were varied in a wide range of rotating velocities and superposed mass flow rates.

2D PIV flow measurements were performed in order to obtain a radial distribution of the tangential velocity, results were used to validate numerical simulations aimed at understanding the admission system effect on the swirl distribution.

Heat transfer coefficient distribution along the stator disk has been evaluated performing a steady state technique exploiting Thermo-chromic Liquid Crystals (TLC).

Tests have been performed varying the superposed mass flow rate up to reaching the condition of cavity completely sealed, further increase of the mass flow rate showed to reduce the effect of the rotation.

Working conditions were set in order to investigate cases missing in open literature, however few tests performed in similarity with other researches provided comparable results.
A Rotordynamic, Thermal, and Thrust Load Performance Gas Bearing Test Rig and Test Results for Tilting Pad Journal Bearings and Spiral Groove Thrust Bearings
Authors: Rimpel Aaron M. , Vannini Giuseppe , Kim Jongsoo
Published: September 2016

A high speed gas bearing test rig was developed to characterize rotordynamic, thermal, and thrust load performance of gas bearings being developed for an oil-free turboexpander. The radial bearings tested in this paper were tilting pad journal bearings with radial compliance features that allow the bearing bore to increase to accommodate shaft growth, and the thrust bearings were a spiral groove type with axial compliance features. The thrust bearing accounts for over 90% of the combined bearing power consumption, which has a cubic relationship with speed and increases with case pressure. Radial bearing circumferential pad temperature gradients increased approximately with speed to the fourth or fifth power, with slightly higher temperature rise for lower case pressure. Maximum steady state bearing pad temperatures increase with increasing speed for similar cooling mass flow rates; however, only the thrust bearing showed a significant increase in temperature with higher case pressure. The thrust bearings were stable at all speeds, but the load capacity was found to be lower than anticipated, apparently due to pad deformations caused by radial temperature gradients in the stator. More advanced modeling approaches have been proposed to better understand the thrust bearing thermal behavior and to improve the thrust bearing design. Finally, the radial bearings tested were demonstrated to be stable up to the design speed of 130 krpm, which represents the highest surface speed for tilting pad gas bearings tested in the literature.
Effects of Contact Mistuning on Shrouded Blisk Dynamics
Authors: Mitra Mainak , Zucca Stefano , Epureanu Bogdan I.
Published: September 2016

Mistuning commonly refers to non-cyclically symmetric variations in such an otherwise cyclically-symmetric structure. Mistuning in a blisk due to variations in blade materials and geometry have been studied extensively and are known to have a significant impact on the forced response of blisks. However, mistuning can also arise due to variations at contact interfaces within a blisk with friction damping mechanisms such as under platform dampers or shrouds. Past literature analyzing the effect of this source of contact mistuning is limited, particularly by the use of lumped or single-node contacts at each sector to shorten analysis times. In this paper, we aim to better understand the specific effects of parameter variations across contact interfaces on an otherwise tuned blisk. A blisk with shroud to shroud contacts is considered. Accurate representation of microslip phenomena are incorporated in the analysis by modeling multiple localized node to node contact models at contact surfaces on each blisk sector. Contact stiffnesses which dictate the friction damping dynamics of the shrouds are chosen as the mistuning parameters. The harmonic balance method is used to solve for forced responses. We analyze cases with random patterns of contact stiffnesses in different microslip regimes in the proximity of different modal regions. Probabilistic analysis of nonlinear contact responses are carried out close to a linear region where comparatively high amplification factors are observed. Statistics are also developed for linear cases and compared with the nonlinear case to qualify the dependence of amplification factors of nonlinear forced responses on the level of microslip and on the variance of contact parameters.
Impact of Skin Friction, Tip Clearance and Trailing Edge Losses on Small Scale Cryogenic Axial Turbine Performance
Authors: Khalil Khalil M. , Mahmoud S. , Al-Dadah R. K. , Al Jubori Ayad , Rahbar K.
Published: September 2016

Cryogenic Energy Storage (CES) technology which uses liquid air/nitrogen as energy carrier has attracted considerable attention recently due to its high exergy density (762kJ/kg) compared to other energy storage technologies. Liquid air/nitrogen occupies about 1/700 of the volume of its gaseous phase making it easier to store and transport. The stored energy can be recovered through a direct expansion process where the expander design and performance have a major effect on the efficiency of the energy conversion process. In this work the effects of surface roughness, tip clearance and trailing edge thickness on the performance of a small scale (tip diameter 40mm, mass flow rate 0.3 kg/s) axial cryogenic turbine have been investigated using mean line 1D analysis and ANSYS CFX 3D modelling where limited data available in the literature. Results showed that stator surface roughness has the highest impact on the turbine performance, where power output and turbine efficiency were significantly reduced as the roughness increased. For example at 20000RPM (design point) with stator roughness value of 0.5mm the efficiency and power output were 87.2% and 1197.7 W while for the same roughness on rotor blade the efficiency and power output were 89.34% and 1198.59 W. Regarding the effect of tip clearance, the efficiency decreases by 2% as the tip clearance increases from 0.35mm to 1mm.
Flutter Generation and Control Using Mistuning in a Turbine Rotating Rig
Authors: Corral Roque , Beloki Josu , Calza Paolo , Elliot Robert
Published: September 2016

The paper describes a free-flutter experiment on a stand-alone low-pressure turbine bladed rotor in a high-speed rotating wind tunnel together with the most relevant design decisions and solutions obtained for a low-reduced frequency cantilever shrouded rotor blade design. The test rotor underwent an experimental campaign with independent control of the shaft speed, pressure ratio and air density levels. Measurements were obtained entirely by means of non-intrusive techniques such as blade tip timing optical probes, and unsteady pressure transducers located in the outer casing of the rig downstream of the rotor. The bladed rotor was designed to flutter under a wide range of operating conditions. The independent effects of the shaft speed and the air density level were thoroughly investigated. It was concluded that, firstly, the higher the density level the higher the level of instability and, secondly, that the vibration amplitude of the rotor blade exhibits a maximum with the shaft speed.

In addition the rotor blades were designed in such a way that additional masses could be mounted in the tip-shrouds to create arbitrary mistuning patterns. Two different mistuning patterns were tested, the first consisted of a classical alternate mistuning pattern designed to suppress flutter whereas a second pattern was designed to halve the vibration amplitude of the tuned bladed-disk. Both objectives were successfully achieved during the experiment.
Coordinated Operation of Centrifugal Compressors in Series via Model Predictive Control
Authors: Mercangöz Mehmet , Stefani Andrea , Cortinovis Andrea
Published: September 2016

This paper investigates the control challenges in the operation of centrifugal compressors in series configuration, which arise from the interactions of the different control loops for process and anti-surge control. The investigation is carried out with simulations, where two compressors in series are considered to represent the simplest possible case for systems analysis. The simulations are based on a well-known nonlinear compressor model to represent the plant behavior as close to reality as possible. The paper starts with the derivation of linear transfer functions from step response analysis, which are used to develop both advanced decentralized control solutions using loop decoupling schemes as well as a model predictive controller (MPC). The various alternative control strategies are then investigated by introducing a typical downstream disturbance case that pushes the compressors towards surge conditions while creating interactions among all control loops. The simulation results are analyzed to determine the advantages and the shortcomings of the different control strategies. The MPC based approach stands out as a high performance alternative to traditional control schemes relying on simple feedback and feedforward elements.
Wet Compression: Performance Test of a 3D Impeller and Validation of Predictive Model
Authors: Ferrara Veronica , Bakken Lars E. , Falomi Stefano , Sassanelli Giuseppe , Bertoneri Matteo , Scotti del Greco Alberto
Published: September 2016

In the last few years wet compression has received special attention from the oil and gas industry. Here, the development and implementation of new subsea solutions are important focus areas to increase production and recovery from existing fields. This new technology will contribute to exploitation of small and remote fields and access in very deep water. In this regard liquid tolerance represents a viable option to reduce the cost of a subsea compression station bringing considerable simplification to the subsea process itself. However, the industry may experience some drawbacks: the various levels of liquid presence may create operational risk for traditional compressors; the liquid may cause mechanical damage because of erosion and corrosion of the internal units and the compressor performance might be affected too. The experimental investigation conducted in the study considers dry and wet conditions in a laboratory setup to understand how the presence of liquid influences the stage performance. The test campaign has been carried out at the Norwegian University of Science and Technology, NTNU, in Trondheim, to assess the performance and operating range of a tridimensional impeller when processing a mixture of gas and liquid phases. Experimental results allowed validating the OEM internal prediction code for compressors’ performance in wet conditions. Finally, the effect of liquid on machine operability has been assessed through a left-limit investigation by means of dynamic pressure probes readings in order to evaluate the stall/surge behaviour for different values of liquid mass fraction.
Experimental Characterization of the Vane Heat Flux Under Pulsating Trailing-Edge Blowing
Authors: Saavedra J. , Paniagua G. , Saracoglu B. H.
Published: September 2016

The steady improvement of aircraft engine performance has led towards more compact engine cores with increased structural loads. Compact single-stage high-pressure turbines allow high power extraction, operating in the low supersonic range. The shock waves formed at the airfoil trailing edge contribute substantially to turbine losses, mainly due to the shock-boundary layer interactions as well as high-frequency forces on the rotor. We propose to control the vane trailing edge shock interaction with the downstream rotor, using a pulsating vane-trailing-edge-coolant at the rotor passing frequency.

A linear cascade of transonic vanes was investigated at different Mach numbers, ranging from subsonic to supersonic regimes (0.8, 1.1) at two engine representative Reynolds numbers (4 and 6 million). The steady and unsteady heat flux was retrieved using thin-film 2-layered gauges. The complexity of the tests required the development of an original heat transfer post-processing approach. In a single test, monitoring the heat flux data and the wall temperature we obtained the adiabatic wall temperature and the convective heat transfer coefficient.

The right-running trailing edge shock wave impacts on the neighboring vane suction side. The impact of the shock wave on the boundary layer creates a separation bubble, which is very sensitive to the intensity and angle of the shock wave. Increasing the coolant blowing rate induces the shock to be less oblique, moving the separation bubble upstream. A similar effect is caused by the pulsations of the coolant.
Comparative STM analysis of C60 and C70 fullerene adsorption sites on pristine and Al-modified Si(111)7 × 7 surfaces
Authors: Mararov Vsevolod V. , Gruznev Dimitry V. , Bondarenko Leonid V. , Tupchaya Alexandra Y. , Zotov Andrey V. , Saranin Alexander A.
Published: September 2016

Using scanning tunneling microscopy observations, preferable adsorption sites of C60 and C70 fullerenes on pristine Si(111)7 × 7 and Al-modified Si(111)α–7 × 7-Al surfaces at 300 and 450 K were determined. The C60 and C70 molecules display similar, albeit not identical, adsorption behavior while the most essential variance is related with the hosting surfaces, pristine 7×7 or α–7 × 7-Al. Both C60 and C70 prefer to occupy positions above the Si rest atoms upon adsorption onto Si(111)7 × 7 at 300 K and change their preferable sites for those located at the Si edge adatom at 450 K, that is plausibly accompanied by releasing the Si adatom. Upon C60 and C70 adsorption onto Si(111)α–7 × 7-Al surface at 300 K, the fullerenes prefer to occupy the asymmetric sites at the dimer rows. At 450 K, the C70 fullerenes preserve this location, while about half of the C60 fullerenes change it for that at the corner Si adatom position. The present experimental data set serves as a useful basis for theoretical analysis.
A robust empirical parametrization of proton stopping power using dual energy CT
Authors: Taasti Vicki T. , Petersen Jørgen B. B. , Muren Ludvig P. , Thygesen Jesper , Hansen David C.
Published: September 2016

Purpose

In this study the authors present a new method for estimation of proton stopping power ratios (SPRs) using dual energy CT (DECT), which is robust toward CT noise. The authors propose a parametrization for SPR based directly on the CT numbers in a DECT image set, whereby the intermediate steps of estimating the relative electron density, ρe, and mean excitation energy, I, are avoided.

Methods

The SPR parametrization proposed in this study is a purely empirical fit based on the theoretical SPR values for a list of 34 reference human tissues. To investigate the SPR estimation made with this new method the authors performed a calibration and an evaluation with the method. The authors initially calculated CT numbers using CT energy spectrum characterization parameters obtained from calibration based on a Gammex 467 electron density calibration phantom. These CT numbers were fitted to the theoretical SPR for the reference human tissues using the new SPR parametrization presented in this study. The method was evaluated based on theoretical CT numbers for the reference human tissues. The root‐mean‐square error (RMSE) of the SPR and the proton range error from the continuous slowing down approximation were calculated for the reference human tissues. To test the stability of the parametrization the authors varied the density and elemental composition of the reference human tissues and calculated their new SPR estimates. Further, clinically realistic noise values were added to the theoretical CT numbers to investigate how CT noise affected the estimated water equivalent range through 10 cm of the reference human tissues. All results for the new SPR parametrization were compared to the results obtained using two previously published DECT methods for SPR estimation. Comparisons were also made to a single energy CT (SECT) SPR estimation method, the stoichiometric method, which is commonly used in clinical practise for proton therapy treatment planning.

Results

The RMSE for the SPR of the 34 reference human tissues using the new SPR parametrization was 0.12%, compared to 0.19% and 0.28% for the two previously published DECT methods. The SPR parametrization was more stable toward variations of the calcium content in the reference human tissues, but less stable toward density variations and changes to the hydrogen content than the two other DECT methods. When adding noise to the theoretical CT numbers the SPR parametrization gave the lowest water equivalent range errors of all four tested SPR estimation methods (maximum error reduced to 0.4 mm). In all cases tested, the new SPR parametrization outperformed the SECT stoichiometric method.

Conclusions

The new SPR parametrization gave lower RMSEs than the two other published DECT methods, and was in particular more robust against added noise. The method has potential for reducing range uncertainty margins in treatment planning of proton therapy.
One-dimensional light localization with classical scatterers: An advanced undergraduate laboratory experiment
Authors: Kemp K. J. , Barker S. , Guthrie J. , Hagood B. , Havey M. D.
Published: September 2016

The phenomenon of electronic wave localization through disorder remains an important area of fundamental and applied research. Localization of all wave phenomena, including light, is thought to exist in a restricted one-dimensional geometry. We present here a series of experiments to illustrate, using a straightforward experimental arrangement and approach, the localization of light in a quasi-one-dimensional physical system. In the experiments, reflected and transmitted light from a stack of glass slides of varying thickness reveals an Ohm's law type behavior for small thicknesses, and evolution to exponential decay of the transmitted power for larger thicknesses. For larger stacks of slides, a weak departure from one-dimensional behavior is also observed. The experiment and analysis of the results, showing many of the essential features of wave localization, is relatively straightforward, economical, and suitable for laboratory experiments at an undergraduate level.
Myosin light chains 9 and 12 are functional ligands for CD69 that regulate airway inflammation
Authors: Hayashizaki Koji , Kimura Motoko Y. , Tokoyoda Koji , Hosokawa Hiroyuki , Shinoda Kenta , Hirahara Kiyoshi , Ichikawa Tomomi , Onodera Atsushi , Hanazawa Asami , Iwamura Chiaki , Kakuta Jungo , Muramoto Kenzo , Motohashi Shinichiro , Tumes Damon J. , Iinuma Tomohisa , Yamamoto Heizaburo , Ikehara Yuzuru , Okamoto Yoshitaka , Nakayama Toshinori
Published: September 2016

CD69 on activated T cells interacts with Myl9/12 expressed in inflamed airways, establishing tissue inflammation.
Unveiling the molecular details of plant signaling
Authors: Gough Nancy R.
Published: September 2016

Signaling research that leads to the molecular understanding of plant physiology is necessary to feed the world.
Reversible acetylation in brassinosteroid signaling
Authors: Gough Nancy R.
Published: September 2016

Deacetylation of the kinase BIN2 by HDA6 promotes brassinosteroid signaling in plants.
Inhibition of ileal bile acid uptake protects against nonalcoholic fatty liver disease in high-fat diet–fed mice
Authors: Rao Anuradha , Kosters Astrid , Mells Jamie E. , Zhang Wujuan , Setchell Kenneth D. R. , Amanso Angelica M. , Wynn Grace M. , Xu Tianlei , Keller Brad T. , Yin Hong , Banton Sophia , Jones Dean P. , Wu Hao , Dawson Paul A. , Karpen Saul J.
Published: September 2016

Inhibition of the ileal bile acid transporter treats multiple features of nonalcoholic steatohepatitis in high-fat diet–fed mice.
IVIG-mediated protection against necrotizing pneumonia caused by MRSA
Authors: Diep Binh An , Le Vien T. M. , Badiou Cedric , Le Hoan N. , Pinheiro Marcos Gabriel , Duong Au H. , Wang Xing , Dip Etyene Castro , Aguiar-Alves Fábio , Basuino Li , Marbach Helene , Mai Thuy T. , Sarda Marie N. , Kajikawa Osamu , Matute-Bello Gustavo , Tkaczyk Christine , Rasigade Jean-Philippe , Sellman Bret R. , Chambers Henry F. , Lina Gerard
Published: September 2016

Human intravenous immunoglobulin contains specific antitoxin antibodies that protect against necrotizing pneumonia caused by MRSA in a rabbit model.
Boosting translational research in the U.K.
Authors: Anandagoda Nelomi , Lord Graham M.
Published: September 2016

Investment in national infrastructure is critical for growth in early-phase translational research and experimental medicine.
Outbreak of OXA-48-Producing Klebsiella pneumoniae Involving a Sequence Type 101 Clone in Batna University Hospital, Algeria
Authors: Loucif Lotfi , Kassah-Laouar Ahmed , Saidi Mahdia , Messala Amina , Chelaghma Widad , Rolain Jean-Marc
Published: September 2016

Seven nonredundant ertapenem-resistant
Klebsiella pneumoniae
isolates were collected between May 2014 and 19 January 2015 in the nephrology and hematology units of Batna University Hospital in Algeria. All strains coproduced the
bla
OXA-48
,
bla
CTX-M-15
,
bla
SHV-1
, and
bla
TEM-1D
genes. Six of these isolates belonged to the pandemic clone sequence type 101 (ST101). The
bla
OXA-48
gene was located on a conjugative IncL/M-type plasmid. This is the first known outbreak of OXA-48-producing
K. pneumoniae
isolates involving an ST101 clone in Batna University Hospital.
Antiviral Nucleotide Incorporation by Recombinant Human Mitochondrial RNA Polymerase Is Predictive of Increased
In Vivo
Mitochondrial Toxicity Risk
Authors: Fenaux Martijn , Lin Xiaodong , Yokokawa Fumiaki , Sweeney Zachary , Saunders Oliver , Xie Lili , Lim Siew Pheng , Uteng Marianne , Uehara Kyoko , Warne Robert , Gang Wang , Jones Christopher , Yendluri Satya , Gu Helen , Mansfield Keith , Boisclair Julie , Heimbach Tycho , Catoire Alexandre , Bracken Kathryn , Weaver Margaret , Moser Heinz , Zhong Weidong
Published: September 2016

Nucleoside or nucleotide inhibitors are a highly successful class of antivirals due to selectivity, potency, broad coverage, and high barrier to resistance. Nucleosides are the backbone of combination treatments for HIV, hepatitis B virus, and, since the FDA approval of sofosbuvir in 2013, also for hepatitis C virus (HCV). However, many promising nucleotide inhibitors have advanced to clinical trials only to be terminated due to unexpected toxicity. Here we describe the
in vitro
pharmacology of compound 1, a monophosphate prodrug of a 2′-ethynyluridine developed for the treatment of HCV. Compound 1 inhibits multiple HCV genotypes
in vitro
(50% effective concentration [EC
50
], 0.05 to 0.1 μM) with a selectivity index of >300 (50% cytotoxic concentration [CC
50
], 30 μM in MT-4 cells). The active triphosphate metabolite of compound 1, compound 2, does not inhibit human α, β, or γ DNA polymerases but was a substrate for incorporation by the human mitochondrial RNA polymerase (POLRMT). In dog, the oral administration of compound 1 resulted in elevated serum liver enzymes and microscopic changes in the liver. Transmission electron microscopy showed significant mitochondrial swelling and lipid accumulation in hepatocytes. Gene expression analysis revealed dose-proportional gene signature changes linked to loss of hepatic function and increased mitochondrial dysfunction. The potential of
in vivo
toxicity through mitochondrial polymerase incorporation by nucleoside analogs has been previously shown. This study shows that even moderate levels of nucleotide analog incorporation by POLRMT increase the risk of
in vivo
mitochondrial dysfunction. Based on these results, further development of compound 1 as an anti-HCV compound was terminated.
Triazole Substitution of a Labile Amide Bond Stabilizes Pantothenamides and Improves Their Antiplasmodial Potency
Authors: Howieson Vanessa M. , Tran Elisa , Hoegl Annabelle , Fam Han Ling , Fu Jonathan , Sivonen Kate , Li Xiao Xuan , Auclair Karine , Saliba Kevin J.
Published: September 2016

The biosynthesis of coenzyme A (CoA) from pantothenate and the utilization of CoA in essential biochemical pathways represent promising antimalarial drug targets. Pantothenamides, amide derivatives of pantothenate, have potential as antimalarials, but a serum enzyme called pantetheinase degrades pantothenamides, rendering them inactive
in vivo
. In this study, we characterize a series of 19 compounds that mimic pantothenamides with a stable triazole group instead of the labile amide. Two of these pantothenamides are active against the intraerythrocytic stage parasite with 50% inhibitory concentrations (IC
50
s) of ∼50 nM, and three others have submicromolar IC
50
s. We show that the compounds target CoA biosynthesis and/or utilization. We investigated one of the compounds for its ability to interact with the
Plasmodium falciparum
pantothenate kinase, the first enzyme involved in the conversion of pantothenate to CoA, and show that the compound inhibits the phosphorylation of [
14
C]pantothenate by the
P. falciparum
pantothenate kinase, but the inhibition does not correlate with antiplasmodial activity. Furthermore, the compounds are not toxic to human cells and, importantly, are not degraded by pantetheinase.
Opening the Channel: the Two Functional Interfaces of Pseudomonas aeruginosa OpmH with the Triclosan Efflux Pump TriABC
Authors: Ntreh Abigail T. , Weeks Jon W. , Nickels Logan M. , Zgurskaya Helen I.
Published: September 2016

TriABC-OpmH is an efflux pump from
Pseudomonas aeruginosa
with an unusual substrate specificity and protein composition. When overexpressed, this pump confers a high level of resistance to the biocide triclosan and the detergent SDS, which are commonly used in combinations for antimicrobial treatments. This activity requires an RND transporter (TriC), an outer membrane channel (OpmH), and two periplasmic membrane fusion proteins (TriA and TriB) with nonequivalent functions. In the active complex, TriA is responsible for the recruitment of OpmH, while TriB is responsible for stimulation of the transporter TriC. Here, we used the functional and structural differences between the two membrane fusion proteins to link their functional roles to specific interactions with OpmH. Our results provide evidence that the TriB-dependent stimulation of the TriC transporter is coupled to opening of the OpmH aperture through binding to the interprotomer groove of OpmH.

IMPORTANCE
Multidrug efflux transporters are important contributors to intrinsic and acquired antibiotic resistance in clinics. In Gram-negative bacteria, these transporters have a characteristic tripartite architecture spanning the entire two-membrane cell envelope. How such complexes are assembled and how the reactions separated in two different membranes are coupled to provide efficient efflux of various compounds across the cell envelope remain unclear. This study addressed these questions, and the results suggest a mechanism for functional integration of drug efflux by the inner membrane transporter and opening of the channel for transport across the outer membrane.
Adenovirus Early Proteins and Host Sumoylation
Authors: Sohn Sook-Young , Hearing Patrick
Published: September 2016

The human adenovirus genome is transported into the nucleus, where viral gene transcription, viral DNA replication, and virion assembly take place. Posttranslational modifications by small ubiquitin-like modifiers (SUMOs) are implicated in the regulation of diverse cellular processes, particularly nuclear events. It is not surprising, therefore, that adenovirus modulates and utilizes the host sumoylation system. Adenovirus early proteins play an important role in establishing optimal host environments for virus replication within infected cells by stimulating the cell cycle and counteracting host antiviral defenses. Here, we review findings on the mechanisms and functional consequences of the interplay between human adenovirus early proteins and the host sumoylation system.
Domains relating to the everyday impact of hearing loss, as reported by patients or their communication partner(s): protocol for a systematic review
Authors: Vas Venessa , Akeroyd Michael A , Hall Deborah A
Published: September 2016

Introduction

Hearing loss is a highly prevalent condition that affects around 1 in 6 people in the UK alone. This number is predicted to rise by the year 2031 to a staggering 14.5 million people due to the ageing population of the UK. Currently, the most common intervention for hearing loss is amplification with hearing aid(s) which serve to address the issue of audibility due to hearing loss, but cannot reverse its effects. The consequences of hearing loss are multifaceted, as it is a complex condition that can detrimentally affect various aspects of an individual's life, including communication and personal relationships. The scope of these reported issues is so broad that it calls on the need for patient-centred management plans that are tailored to each patient as well as appropriate measures to assess intervention benefit. It is unclear whether current outcome instruments adequately match what patients report as the most important problems for them.

Methods and analysis

The systematic review aims to capture existing knowledge about patients and their communication partner's perspective on the everyday impact of hearing loss. Methods are defined according to the Preferred Reporting Items for Systematic reviews and Meta-analyses for Protocols (PRISMA-P) 2015.

Ethics and dissemination

No ethical issues are foreseen. Findings will be reported in student's thesis as well as at national and international ENT/audiology conferences and in a peer-reviewed journal.

Systematic review registration number

PROSPERO CRD42015024914.
BET 2: Acupuncture and fibromyalgia
Authors: Goldie Laura , Hogg Kerstin
Published: September 2016

A shortcut review was carried out to see if acupuncture is an effective pain treatment in fibromyalgia. One Cochrane review and five subsequent papers and conference abstracts were identified. There are no large studies addressing this question and acupuncture has been compared with many different treatment modalities. Acupuncture may be a valid treatment for pain in fibromyalgia, but more research is required to validate this.
Abstracts from international Emergency Medicine journals
Authors: Weber Ellen J
Published: September 2016

Editor's note: EMJ has partnered with the journals of multiple international emergency medicine societies to share from each a highlighted research study, as selected by their editors.
Implementing checklists in practice
Authors: Oxtoby Catherine , Mossop Liz
Published: September 2016

Use of checklists in a clinical setting can improve both the quality and safety of the care that a patient receives. In the September issue of In Practice, Catherine Oxtoby and Liz Mossop discussed clinical governance and the use of checklists in human medicine and the lessons for veterinary practice (IP, September 2016, pp 408–410). Here, they look at how checklists can be implemented in a veterinary setting.
Autoinflammatory diseases: update on classification diagnosis and management
Authors: Pathak Shelly , McDermott Michael F , Savic Sinisa
Published: September 2016

The spectrum of systemic autoinflammatory disorders broadens continually. In part, this is due to the more widespread application of massive parallel sequencing, helping with novel gene discovery in this and other areas of rare diseases. Some of the conditions that have been described fit neatly into a conventional idea of autoinflammation. Others, such as interferon-mediated autoinflammatory diseases, are broadening the concept which we consider to be autoinflammatory disorders. There is also a widening of the clinical phenotypes associated with certain genetic mutations, as genetic testing is used more regularly and increasing numbers of patients are screened. It is also increasingly evident that both autoinflammatory and autoimmune problems are frequently seen as complications of primary immunodeficiency disorders. The aim of this review is to provide an update on some recently discovered conditions and to discuss how these disorders help to define the concept of autoinflammation. The review will also cover recent discoveries in the biology of innate-immune-mediated inflammation and describe how this has provided the biological rationale for using anti-interleukin-1 therapies in the treatment of many such conditions. Finally, we discuss the importance of recognising somatic mutations as causes of autoinflammatory clinical phenotypes and provide practical advice on how this could be tackled in everyday clinical practice.
Significance of coexistent granulomatous inflammation and lung cancer
Authors: Dagaonkar Rucha S , Choong Caroline V , Asmat Atasha Binti , Ahmed Dokeu Basheer A , Chopra Akhil , Lim Albert Y H , Tai Dessmon Y H , Kor Ai Ching , Goh Soon Keng , Abisheganaden John , Verma Akash
Published: September 2016

Aims

Coexistence of lung cancer and granulomatous inflammation in the same patient confuses clinicians. We aimed to document the prevalence, clinicopathological features, treatment outcomes and prognosis in patients with coexisting granulomatous inflammation undergoing curative lung resection for lung cancer, in a tuberculosis (TB)-endemic country.

Methods

An observational cohort study of patients with lung cancer undergoing curative resection between 2012 and 2015 in a tertiary centre in Singapore.

Results

One hundred and twenty-seven patients underwent lung resection for cancer, out of which 19 (14.9%) had coexistent granulomatous inflammation in the resected specimen. Median age was 68 years and 58.2% were males. Overall median (range) survival was 451 (22–2452) days. Eighteen (14%) patients died at median duration of 271 days after surgery. The postsurgery median survival for those alive was 494 (29–2452) days in the whole group. Subgroup analysis did not reveal any differences in age, gender, location of cancer, radiological features, type of cancer, chemotherapy, history of TB or survival in patients with or without coexistent granulomatous inflammation.

Conclusions

Incidental detection of granulomatous inflammation in patients undergoing lung resection for cancer, even in a TB-endemic country, may not require any intervention. Such findings may be due to either mycobacterial infection in the past or ‘sarcoid reaction’ to cancer. Although all patients should have their resected specimen sent for acid-fast bacilli culture and followed up until the culture results are reported, the initiation of the management of such patients as per existing lung cancer management guidelines does not affect their outcome adversely.
A survey on internet usage and online learning behaviour among medical undergraduates
Authors: Venkatesh Soma , Chandrasekaran Venkatesh , Dhandapany Gunasekaran , Palanisamy Soundararajan , Sadagopan Srinivasan
Published: September 2016

Aim

To determine the magnitude and pattern of internet usage by undergraduate medical students to retrieve medical information.

Materials and methods

A pretested questionnaire-based survey was conducted among undergraduate medical students who were willing to participate. The institute ethics committee approved the study. The responses of students to the questionnaire were analysed using VassarStats online statistical programme. Categorical variables were expressed as proportions. To determine the significance of the difference between proportions, the χ2 test or Fisher’s exact test was used. Log-linear analysis was performed for significance of association among interacting variables. A p value <0.05 was considered significant.

Results

A total of 115 undergraduate medical students participated in the survey. The response was 100% and involved mainly IX and VIII semester students. Internet usage was found to be 97.4%. Of the students interviewed, 35.7% were frequent internet users and 57.4% used their mobile phones to access the internet. The majority (60.9%) had their own portable 3G internet connection. Monthly expenditure for the majority (82.6%) was less than 1000 Indian Rupees per month. The most popular medical site accessed by students was Medscape, followed by Wikipedia and WebMD. Of the students studied, 8% had attended one or more online continuing medical education programmes. On log-linear analysis, a linear relationship was found for medical time and social time.

Conclusions

An encouraging trend is seen in the use of the internet by medical students to access medical information, but this has not translated into improved online learning behaviour.
Association between bacterial vaginosis and partner concurrency: a longitudinal study
Authors: Kenyon Chris R , Buyze Jozefien , Klebanoff Mark , Brotman Rebecca M
Published: September 2016

Objectives

The study aimed to test if there was an association between prevalent bacterial vaginosis (BV) and women reporting that their partner had other partners at the same time (partner concurrency). This association has not been assessed in a longitudinal cohort.

Methods

The Longitudinal Study of Vaginal Flora recruited a cohort of 3620 non-pregnant women aged 15–44 years who presented for routine primary healthcare at 12 clinics in Birmingham, Alabama. Behavioural questionnaires and vaginal smears were obtained quarterly for a year and BV was defined by a Nugent score 7 or higher as well as Amsel criteria. Mixed effects logistic regression was used to assess the relationship between prevalent BV and reporting that one's partner had other partners in the preceding 3–6 months time interval.

Results

Nugent score prevalent BV was associated with both reporting that one's partner definitely (adjusted OR (aOR) 1.5; 95% CI 1.2 to 1.8) and possibly (aOR 1.5; 95% CI 1.2 to 1.8) engaged in partner concurrency in the preceding 3–6 months time period. Prevalent BV diagnosed by Amsel criteria was similar.

Conclusions

A diagnosis of prevalent BV was associated with reporting that one's partner possibly or definitely engaged in partner concurrency.
The Cost and Benefits of Coordination Programming: Two Case Studies in Concurrent Collections and S-NET
Authors: Zaichenkov Pavel , Tveretina Olga , Shafarenko Alex , Gijsbers Bert , Grelck Clemens
Published: September 2016

This is an evaluation study of the expressiveness provided and the performance delivered by the coordination language S-NET in comparison to Intel’s Concurrent Collections (CnC). An S-NET application is a network of black-box compute components connected through anonymous data streams, with the standard input and output streams linking the application to the environment. Our case study is based on two applications: a face detection algorithm implemented as a pipeline of feature classifiers and a numerical algorithm from the linear algebra domain, namely Cholesky decomposition. The selected applications are representative and have been selected by Intel researchers as evaluation testbeds for CnC in the past. We implement various versions of both algorithms in S-NET and compare them with equivalent CnC implementations, both with and without tuning, previously published by the CnC community. Our experiments on a large-scale server system demonstrate that S-Net delivers very similar scalability and absolute performance on the studied examples as tuned CnC codes do, even without specific tuning. At the same time, S-Net does achieve a much more complete separation of concerns between compute and coordination layers than CnC even intends to.