bluuebunny/crossref_metadata_2025 huggingface dataset:
Ceramic Stationary Gas Turbine Development Program — Design and Test of a First Stage Ceramic Nozzle
Authors: Faulder Leslie , McClain John , Edwards Bryan , Parthasarathy Vijay
Published: December 2014

The goal of the Ceramic Stationary Gas Turbine(CSGT) Development Program, under the sponsorship of the United States Department of Energy (DOE), Office of Industrial Technologies (OIT), is to improve the performance (fuel efficiency, output power, exhaust emissions) of stationary gas turbines in cogeneration through the selective replacement of hot section components with ceramic parts. Phase II of this program includes detailed engine and component design, procurement and testing. This paper will review the design and test of the first stage ceramic nozzle for the Centaur 50S engine. For this test an uncooled monolithic ceramic nozzle made from SN-88 silicon nitride(NGK Insulators Ltd.) was used.

A major challenge in the successful introduction of ceramic parts into a gas turbine is the design of the interface between the ceramic parts and metallic components. The design and attachment of the ceramic nozzle was greatly influenced by these considerations. Metallic components in the stationary structure of the turbine have been added or redesigned to retrofit the ceramic nozzle into the all metallic Centaur 50S engine.

This paper will also discuss special handling and assembly techniques used to install the ceramic nozzle into the engine. Trial assemblies were used in the engine build process, this proved most beneficial in identifying problems and reducing the risk of damage to the ceramic nozzles. Assembly techniques were designed to reduce assembly loads and to eliminate blind assemblies.

Before installing any ceramic nozzles into the engine they were first required to successfully pass both mechanical and thermal proof tests. Details of these proof tests and the final full load engine test will be described in this paper. The engine test was run at a turbine rotor inlet temperature(TRIT) of 1010°C. Total number of engine starts was six, and the total run time was approximately 10 hours.
Unsteady Flow in a Single Stage Turbine
Authors: Hilditch Mary A. , Smith Graham C. , Singh Udai K.
Published: December 2014

This paper presents unsteady pressure and heat transfer measurements made on a high pressure turbine stage at DERA Pyestock, and compares them with numerical simulations made using the 2D unsteady code UNSFLO. The aim of the work was to evaluate the performance of the code, and to use the predictions to allow a fuller interpretation of the flow physics than could have been achieved from the measurements alone. The unsteady heat transfer and pressure fluctuations around the mid height section of the rotor blade have been examined in detail. Agreement between measured and predicted pressure fluctuations on the rotor was excellent. Interaction with the ngv potential field dominated the pressure surface, while the suction surface showed pressure waves moving forward over the blade, possibly as a result of shock/wake interaction.
A New High Efficiency Gas Turbine for Mechanical Drives
Authors: Wilson Jay M. , Lindenfeld J. William , Vendler Kenna D. , Todman Mike T. , Whinray Brian , Muddiman John W.
Published: December 2014

This paper discusses the design and development program that is taking place to enable the availability in mid 1999 of a unit designated the Coberra 6761. This features the aircraft derivative Rolls-Royce RB211-24G upgrade gas generator and a new close coupled Cooper-Bessemer RT61 three stage power turbine. The paper describes the upgrade of the gas turbine from 28.4MW (38 000 SHP) to 31.8MW (42 600 SHP) ISO output power at over 40% thermal efficiency. Measures taken to maximize reliability and maintainability while reducing cost of ownership are described. The improvements in the gas generator compressors and turbines are detailed. The new design features of the power turbine are reviewed including a new support structure, modular service features and 3D orthogonal airfoil designs. The forthcoming validation program for the entire gas turbine unit is also discussed.
Further Development of the Siemens LPP Hybrid Burner
Authors: Hoffmann Stefan , Judith Hans , Holm Carl-Gunnar
Published: December 2014

Lean premixed (LP) combustion is a proven concept for NOx-reduction in gas turbine systems. Lean premixed liquid fuel systems, also known as LPP (lean premixed prevaporized) systems, however, are more complex, as the fuel has to be atomized, evaporated and premixed prior to combustion and there is a higher risk of autoignition and coking.

The Siemens LPP Hybrid burner, which was introduced into the Halmstadvaerket gas turbine of Sydkraft AB in Sweden in 1993, has since proven its reliability. As the primary design criteria have been maximum reliability and security against flashback, it still has a considerable potential for NOx-Emissions reduction.

The objectives of this paper are to summarize the activities connected with the further development of the LPP Hybrid burner based on the Halmstadvaerket operation experience. These include the introduction of the LPP burner into a new machine generation with ring combustors as well as investigations into the two phase flow phenomena inside the burner.

When the Model VX4.3A gas turbine family was introduced, the LPP Hybrid burner had to be scaled down to fit the different machine sizes. The paper reports on the development steps and first operation experiences with the LPP Hybrid burner system in HBR-combustor machines.

In a concluding chapter, the paper outlines the next steps in the LPP development program. These include further experimental and numerical studies which are partly conducted in a co-operation between Sydkraft AB and Siemens AG.
Ceramic Gas Turbine Technology Development
Authors: Easley Michael L. , Schenk Bjoern , Cai Hongda
Published: December 2014

AlliedSignal Engines is addressing critical concerns slowing commercialization of structural ceramics in gas turbines. The AlliedSignal 331-200[CT] APU test bed features ceramic first-stage nozzles and blades. Fabrication of ceramic components provides manufacturing process demonstration scale-up to minimum levels for commercial viability. Endurance tests and field testing in commercial aircraft will demonstrate component reliability.

Manufacturing scale-up activities showed significant progress in 1997. Subcontractors AlliedSignal Ceramic Components (CC, Torrance, CA) and Kyocera Industrial Ceramics Corporation (KICC, Vancouver, WA), transitioned process refinements to demonstration. CC initiated trial production of 100 nozzles/month. These suppliers are also developing fixed processes to fabricate ceramic integrally-bladed turbine rotors (“blisks”).

Ceramic design technology advanced with carbon particle impact testing supporting impact model verification, and 300 hours successful engine testing of longer-life inserted blade attachment compliant layers. Ceramic turbine nozzles were readied for planned field demonstrations with 473 hours of engine testing.

This work was funded as part of the Turbine Engine Technologies Program by the DoE Office of Transportation Technologies under Contract No. DE-AC02-96EE50454.
Adaptation of the Stuttgart University Altitude Test Facility for BR700 Core Demonstrator Engine Tests
Authors: Schmidt Klaus-J. , Merten Ralph , Menrath Martin , Braig Wolfgang
Published: December 2014

Within the initiative of the German Aerospace Research Programme - Engine 3E Project - the altitude test facility at the University of Stuttgart has been successfully adapted and commissioned as a new facility for BR700 core demonstrator engine tests.

A core demonstrator consists of high pressure components of the engine. The low pressure system, which is not part of the core engine, must be simulated by the test facility itself. This paper describes the technical concept of the computer control system and the procedure in which the core demonstrator, altitude test facility and sub-systems were integrated and tested. The concept consists of:

1. A Master Control System to run the measurement process and to control and monitor the overall test activity.

2. A modified FADEC of a BR700-710 engine with modified control laws to control the core demonstrator.

3. A Facility Controller to control the air conditioning process of the facility-air station and to provide the required core inlet pressure and temperature profiles for the running of the core demonstrator.

4. Various sub-systems for supplying the core engine with lubricating oil, fuel, etc.

The test programme was focussed on evaluating the interaction between the various control systems. It was found that the test facility fulfills the requirements of providing the transient pressure and temperature profiles for rapid accelerations and decelerations during core engine test.
Predicted Influence of Intake Acoustics Upon Part-Speed Fan Flutter
Authors: Chew J. W. , Vahdati M. , Imregun M.
Published: December 2014

While it is known that the occurrence of flutter is dominated by aerodynamics, it also depends on such parameters as inlet distortion and acoustics, aerodynamic and mechanical mistuning, and structural damping. It is shown in this paper that recent developments in predictive methods are showing considerable promise and leading to an improved understanding of the controlling parameters. A non-linear coupled structural-fluid approach is described and applied at engine representative conditions. This involves 3D unsteady CFD calculations of the fan and intake flows. Particular emphasis is placed on the influence of intake acoustics. Earlier work on flutter prediction has focused on either the fan assembly without a proper representation of the intake, or the calculation of the acoustic properties of the intake without properly representing the interaction with the fan. The present study includes a combined fan plus intake calculation, the latter being represented via an axisymmetric approximation. With an initial prescribed velocity disturbance of the blades in a 2 nodal diameter mode, the calculations showed a strong response in a 4 nodal diameter mode. Considerable acoustic activity within the duct was also noted. This result was compared with CFD calculations for the full 3D intake geometry. It was concluded that a realistic representation of intake acoustics is required for a full description of the problem.
Simultaneous Single-Shot LIF-Imaging of OH and UHC in a Prevaporized, Partially Premixed, Swirl-Stabilized n-Heptane Flame
Authors: Lachner Rudolf , Theisen Daniel , Fink Rainer , Rist Dieter , Schmid Achim , Bittlinger Gerd
Published: December 2014

The prevaporized, partially premixed, swirl-stabilized n-heptane flame in an atmospheric pressure combustor is investigated using a tuneable KrF excimer laser. Flashing the flame with a laser sheet tuned to the P2(8) line of OH (hydroxyl radical), single-shot images of the laser-induced signals are taken simultaneously with two ICCD-cameras aligned to the same measuring volume. One camera detects mainly the laser-induced fluorescence (LIF) from the 3→2 band of the OH plus signals from UHC (unburned hydrocarbons). Only broad-band emission from UHC is imaged onto the other camera. Comparing the two images, signals stemming from OH and UHC, respectively, can be distinguished. Pictures, taken in various planes along the main flow direction, reveal highly turbulent structures in the flame. High fluorescence signals from OH can obviously be found both in filament-like flame fronts lying between fresh combustible mixtures and hot combustion products as well as in broadened reaction regions.
Active Control of Combustion for Optimal Performance
Authors: Jackson Mathew D. , Agrawal Ajay K.
Published: December 2014

Combustion-zone stoichiometry and fuel-air premixing were actively controlled to optimize the combustor performance over a range of operating conditions. The objective was to maximize the combustion temperature, while maintaining NOx within a specified limit. The combustion system consisted of a premixer located coaxially near the inlet of a water-cooled shroud. The equivalence ratio was controlled by a variable-speed suction fan located downstream. The split between the premixing air and diffusion air was governed by the distance between the premixer and shroud. The combustor performance was characterized by a cost function evaluated from time-averaged measurements of NOx and oxygen concentrations in products. The cost function was minimized by the downhill simplex algorithm employing closed-loop feedback. Experiments were conducted at different fuel flow rates to demonstrate that the controller optimized the performance without prior knowledge of the combustor behavior.
Evolution of the Solar Turbines Titan 130 Industrial Gas Turbine
Authors: Rocha G. , Etheridge C. J.
Published: December 2014

Solar Turbines Incorporated has extended the size-range of its’ turbomachinery products with development of the Titan™ 130 industrial gas turbine. The 13 megawatt-class, simple-cycle machine is designed to produce 13.3 MW (17,800 hp) output power with a thermal efficiency of 34.5% at ISO inlet conditions with no losses. The larger gas turbine is intended to meet increasing market demands in gas compression and mechanical pump-drive industrial applications.

The overall engine design is based on aerodynamic-scale of the 7 MW-class Taurus™ 70 gas turbine with similar operating cycle parameters. The engine configuration consists of hardware that has been scaled from the Taurus 70 and components that are common with the Mars® gas turbine. As with the Taurus 70 and Mars products, the Titan 130 gas turbine features a low emissions combustion system based on Solar’s proven dry, lean-premix, pollution-prevention technology. The enhance system is capable of reducing pollutant emissions over an extended operating range from part-load to full-load conditions.

This paper discusses the evolutionary design of the Titan 130 from the Taurus 70 and Mars gas turbines products. Descriptions of the basic configuration, component scaling techniques and modular design construction are presented.
Leakage Effects in the Rotor Tip-Clearance Region of a Multistage Axial Compressor: Part 1 — Innovative Experiments
Authors: Ivey P. C. , Swoboda M.
Published: December 2014

This paper describes work conducted as part of an experimental and numerical study of leakage effects by numerous Research and Industrial partners. For clarity it is presented in two parts. Part 1 presents measurements of tip-clearance flow for a 3rd stage rotor embedded in a four stage low-speed research compressor. The measurements are innovative and comprise measurements in the rotor relative frame of reference and 3D Laser time-of-flight Anemometry. Both techniques are relevant for improved understanding of multistage compressor flow dynamics and consequently, validated multistage CFD simulations.

In part 2 of this paper (see Politis et al 1997b) it is shown that downstream of the rotor passage the location and size of a tip-clearance vortex, identified from both independent measurement techniques in Part 1, is in good agreement with 3D solutions of the Navier-Stokes equations modelling this compressor. These 3D numerical solutions reveal the tip-clearance flow structure using a multiblock grid technique.
Enhanced photocatalytic performance in atomic layer deposition grown TiO2 thin films via hydrogen plasma treatment
Authors: Sasinska Alexander , Singh Trilok , Wang Shuangzhou , Mathur Sanjay , Kraehnert Ralph
Published: December 2014

The authors report the effect of hydrogen plasma treatment on TiO2 thin films grown by atomic layer deposition as an effective approach for modifying the photoanode materials in order to enhance their photoelectrochemical performance. Hydrogen plasma treated TiO2 thin films showed an improved absorption in the visible spectrum probably due to surface reduction. XPS analysis confirmed the formation of Ti3+ states upon plasma treatment. Hydrogen plasma treatment of TiO2 films enhanced the measured photocurrent densities by a factor of 8 (1 mA/cm2 at 0.8 V versus normal hydrogen electrode) when compared to untreated TiO2 (0.12 mA/cm2). The enhancement in photocurrent is attributed to the formation of localized electronic states in mid band-gap region, which facilitate efficient separation and transportation of photo excited charge carriers in the UV region of electromagnetic spectrum.
InGaN/silicon heterojunction based narrow band near-infrared detector
Authors: Pillai Rajeev , Starikov David , Gandhi Jateen , Debnath Ananya , Li Ruiteng , Boney Christopher , Bensaoula Abdelhak
Published: December 2014

While InGaN devices have shown great potential as photodetectors and light emitting devices in the UV to visible range, extension of their applications to the near-infrared (NIR) region has been less successful due to challenges faced in developing high Indium content InGaN layers. Here, the authors present our results on the development of an InGaN/Silicon heterojunction structure with a > 70% In content in the InGaN layer, showing a measurable response in the NIR range. The achieved results show that the band offset between InGaN, buffer layer and Silicon interface can be used as a mean for fabrication of photodiode structures with spectral sensitivity varying with indium content. However, the authors observed that the resulting photoresponse is still a combination of photoresponses produced by absorption of photons in both InGaN and silicon materials.
Energy conservation and Poynting's theorem in the homopolar generator
Authors: Chyba Christopher F. , Hand Kevin P. , Thomas Paul J.
Published: December 2014

Most familiar applications of Poynting's theorem concern stationary circuits or circuit elements. Here, we apply Poynting's theorem to the homopolar generator, a conductor moving in a background magnetic field. We show that the electrical power produced by the homopolar generator equals the power lost from the deceleration of the rotating Faraday disk due to magnetic braking and review the way that magnetic braking arises within Poynting's theorem.
A free plate model can predict guided modes propagating in tubular bone-mimicking phantoms
Authors: Minonzio Jean-Gabriel , Foiret Josquin , Moilanen Petro , Pirhonen Jalmari , Zhao Zuomin , Talmant Maryline , Timonen Jussi , Laugier Pascal
Published: December 2014

The goal of this work was to show that a non-absorbing free plate model can predict with a reasonable accuracy guided modes measured in bone-mimicking phantoms that have circular cross-section. Experiments were carried out on uncoated and coated phantoms using a clinical axial transmission setup. Adjustment of the plate model to the experimental data yielded estimates for the waveguide characteristics (thickness, bulk wave velocities). Fair agreement was achieved over a frequency range of 0.4 to 1.6 MHz. A lower accuracy observed for the thinnest bone-mimicking phantoms was caused by limitations in the wave number measurements rather than by the model itself.
Physical Activity and School-Age Individuals With Visual Impairments: A Literature Review
Authors: Haegele Justin A. , Porretta David
Published: December 2014

The purpose of this article was to review published research literature on physical activity for school-age individuals with visual impairments by describing study characteristics and major findings. Keyword searches were used to identify articles from electronic databases published from 1982 to June 2013. Eighteen articles met all inclusion criteria, and relevant data such as participants, visual-impairment levels, theory, measurement, and dependent variables were extracted from them. Of the 18 studies, 5 were descriptive, 6 correlational, and 7 were interventions. Only 4 studies explicitly stated a theoretical or conceptual framework. Major findings suggest that low physical activity levels of school-age individuals with visual impairments may be related to perceived participation barriers including the availability of appropriate opportunities rather than visual acuity or educational setting.
Knee Joint Loading During Lineman-Specific Movements in American Football Players
Authors: Lambach Rebecca L. , Young Jay W. , Flanigan David C. , Siston Robert A. , Chaudhari Ajit M.W.
Published: December 2014

Linemen are at high risk for knee cartilage injuries and osteoarthritis. High-intensity movements from squatting positions (eg, 3-point stance) may produce high joint loads, increasing the risk for cartilage damage. We hypothesized that knee moments and joint reaction forces during lineman-specific activities would be greater than during walking or jogging. Data were collected using standard motion analysis techniques. Fifteen NCAA linemen (mean ± SD: height = 1.86 ± 0.07 m, mass = 121.45 ± 12.78 kg) walked, jogged, and performed 3 unloaded lineman-specific blocking movements from a 3-point stance. External 3-dimensional knee moments and joint reaction forces were calculated using inverse dynamics equations. MANOVA with subsequent univariate ANOVA and post hoc Tukey comparisons were used to determine differences in peak kinetic variables and the flexion angles at which they occurred. All peak moments and joint reaction forces were significantly higher during jogging than during all blocking drills (all P < .001). Peak moments occurred at average knee flexion angles > 70° during blocking versus < 44° in walking or jogging. The magnitude of moments and joint reaction forces when initiating movement from a 3-point stance do not appear to increase risk for cartilage damage, but the high flexion angles at which they occur may increase risk on the posterior femoral condyles.
Science Signaling
Podcast: 23 December 2014
Authors: Wood Kris C. , VanHook Annalisa M.
Published: December 2014

Two related studies reveal combination treatments that may overcome drug resistance in cancer.
Endogenous Retroviruses Trigger B Cells
Authors: Mueller Kristen L.
Published: December 2014

Endogenous retroviruses materially contribute to humoral immunity in mice.
Stimulating Fat with Adenosine
Authors: VanHook Annalisa M.
Published: December 2014

Adenosine stimulates brown adipose tissue to expend energy and can induce the “browning” of white adipocytes.
Effect of Asparagine Substitutions in the YXN Loop of a Class C β-Lactamase of Acinetobacter baumannii on Substrate and Inhibitor Kinetics
Authors: Skalweit Marion J. , Li Mei , Taracila Magda A.
Published: December 2014

Class C cephalosporinases are a growing threat, and inhibitors of these enzymes are currently unavailable. Studies exploring the YXN loop asparagine in the
Escherichia coli
AmpC, P99, and CMY-2 enzymes have suggested that interactions between C6′ or C7′ substituents on penicillins or cephalosporins and this Asn are important in determining substrate specificity and enzymatic stability. We sought to characterize the YXN loop asparagine in the clinically important ADC-7 class C β-lactamase of
Acinetobacter baumannii
. Mutagenesis at the N148 position in ADC-7 yields functional mutants (N152G, -S, -T, -Q, -A, and -C) that retain cephalosporinase activity. Using standard assays, we show that N148G, -S, and -T variants possess good catalytic activity toward cefoxitin and ceftaroline but that cefepime is a poor substrate. Because N152 variants of CMY-2, another class C β-lactamase, are more readily inhibited by tazobactam due to higher rates of inactivation, we also tested if the N148 substitutions in ADC-7 would affect inactivation by sulfone inhibitors, sulbactam and tazobactam, class A β-lactamase, and
A. baumannii
penicillin-binding protein (PBP) inhibitors with
in vitro
activity against ADC-7. The 50% inhibitory concentrations (IC
50
s) for tazobactam and sulbactam were improved, with 7-fold and 2-fold reductions, respectively, for the N148S variant. A homology model of the N148S ADC-7 enzyme in a Michaelis-Menten complex with tazobactam showed a loss of interaction between N148 and the sulfone moiety of the inhibitor. We postulate that this may result in more-rapid secondary ring opening of the inhibitor, as the unbound sulfone is an excellent leaving group, leading to more-rapid formation of the stable linearized inhibitor.
Molecular Diagnosis of Fluoroquinolone Resistance in Mycobacterium tuberculosis
Authors: Bernard Christine , Veziris Nicolas , Brossier Florence , Sougakoff Wladimir , Jarlier Vincent , Robert Jérôme , Aubry Alexandra
Published: December 2014

As a consequence of the use of fluoroquinolones (FQ), resistance to FQ has emerged, leading to cases of nearly untreatable and extensively drug-resistant tuberculosis. Mutations in DNA gyrase represent the main mechanism of FQ resistance. A full understanding of the pattern of mutations found in FQ-resistant (FQ
r
) clinical isolates, and of their proportions, is crucial for improving molecular methods for the detection of FQ resistance in
Mycobacterium tuberculosis
. In this study, we reviewed the detection of FQ resistance in isolates addressed to the French National Reference Center for Mycobacteria from 2007 to 2012, with the aim of evaluating the performance of PCR sequencing in a real-life context.
gyrA
and
gyrB
sequencing, performed prospectively on
M. tuberculosis
clinical isolates, was compared for FQ susceptibility to 2 mg/liter ofloxacin by the reference proportion method. A total of 605 isolates, of which 50% were multidrug resistant, were analyzed. The increase in FQ
r
strains among multidrug-resistant (MDR) strains during the time of the study was alarming (8% to 30%). The majority (78%) of the isolates with
gyrA
mutations were FQ
r
, whereas only 36% of those with
gyrB
mutations were FQ
r
. Only 12% of the FQ
r
isolates had a single mutation in
gyrB
. Combined
gyrA
and
gyrB
sequencing led to >93% sensitivity for detecting resistance. The analysis of the four false-positive and the five false-negative results of
gyrA
and
gyrB
sequencing illustrated the actual limitations of the reference proportion method. Our data emphasize the need for combined
gyrA
and
gyrB
sequencing in the investigation of FQ susceptibility in
M. tuberculosis
and challenge the validity of the current phenotype-based approach as the diagnostic gold standard for determining FQ resistance.
Protection against Klebsiella pneumoniae Using Lithium Chloride in an Intragastric Infection Model
Authors: Tsao Nina , Kuo Chih-Feng , Chiu Ching-Chen , Lin Wei-Chen , Huang Wan-Hui , Chen Li-Yang
Published: December 2014

Intragastric
Klebsiella pneumoniae
infections of mice can cause liver abscesses, necrosis of liver tissues, and bacteremia. Lithium chloride, a widely prescribed drug for bipolar mood disorder, has been reported to possess anti-inflammatory properties. Using an intragastric infection model, the effects of LiCl on
K. pneumoniae
infections were examined. Providing mice with drinking water containing LiCl immediately after infection protected them from
K. pneumoniae
-induced death and liver injuries, such as necrosis of liver tissues, as well as increasing blood levels of aspartate aminotransferase and alanine aminotransferase, in a dose-dependent manner. LiCl administered as late as 24 h postinfection still provided protection. Monitoring of the LiCl concentrations in the sera of
K. pneumoniae
-infected mice showed that approximately 0.33 mM LiCl was the most effective dose for protecting mice against infections, which is lower than the clinically toxic dose of LiCl. Surveys of bacterial counts and cytokine expression levels in LiCl-treated mice revealed that both were effectively inhibited in blood and liver tissues. Using
in vitro
assays, we found that LiCl (5 μM to 1 mM) did not directly interfere with the growth of
K. pneumoniae
but made
K. pneumoniae
cells lose the mucoid phenotype and become more susceptible to macrophage killing. Furthermore, low doses of LiCl also partially enhanced the bactericidal activity of macrophages. Taken together, these data suggest that LiCl is an alternative therapeutic agent for
K. pneumoniae
-induced liver infections.
A Novel Inhibitor of Gyrase B Is a Potent Drug Candidate for Treatment of Tuberculosis and Nontuberculosis Mycobacterial Infections
Authors: Locher Christopher P. , Jones Steven M. , Hanzelka Brian L. , Perola Emanuele , Shoen Carolyn M. , Cynamon Michael H. , Ngwane Andile H. , Wiid Ian J. , van Helden Paul D. , Betoudji Fabrice , Nuermberger Eric L. , Thomson John A.
Published: December 2014

New drugs to treat drug-resistant tuberculosis are urgently needed. Extensively drug-resistant and probably the totally drug-resistant tuberculosis strains are resistant to fluoroquinolones like moxifloxacin, which target gyrase A, and most people infected with these strains die within a year. In this study, we found that a novel aminobenzimidazole, VXc-486, which targets gyrase B, potently inhibits multiple drug-sensitive isolates and drug-resistant isolates of
Mycobacterium tuberculosis
in vitro
(MICs of 0.03 to 0.30 μg/ml and 0.08 to 5.48 μg/ml, respectively) and reduces mycobacterial burdens in lungs of infected mice
in vivo
. VXc-486 is active against drug-resistant isolates, has bactericidal activity, and kills intracellular and dormant
M. tuberculosis
bacteria in a low-oxygen environment. Furthermore, we found that VXc-486 inhibits the growth of multiple strains of
Mycobacterium abscessus
,
Mycobacterium avium
complex, and
Mycobacterium kansasii
(MICs of 0.1 to 2.0 μg/ml), as well as that of several strains of
Nocardia
spp. (MICs of 0.1 to 1.0 μg/ml). We made a direct comparison of the parent compound VXc-486 and a phosphate prodrug of VXc-486 and showed that the prodrug of VXc-486 had more potent killing of
M. tuberculosis
than did VXc-486
in vivo
. In combination with other antimycobacterial drugs, the prodrug of VXc-486 sterilized
M. tuberculosis
infection when combined with rifapentine-pyrazinamide and bedaquiline-pyrazinamide in a relapse infection study in mice. Furthermore, the prodrug of VXc-486 appeared to perform at least as well as the gyrase A inhibitor moxifloxacin. These findings warrant further development of the prodrug of VXc-486 for the treatment of tuberculosis and nontuberculosis mycobacterial infections.
Molecular Analysis of Codon 548 in the
rpoB
Gene Involved in Mycobacterium tuberculosis Resistance to Rifampin
Authors: Horng Yu-Tze , Jeng Wen-Yih , Chen Yih-Yuan , Liu Che-Hung , Dou Horng-Yunn , Lee Jen-Jyh , Chang Kai-Chih , Chien Chih-Ching , Soo Po-Chi
Published: December 2014

Most
Mycobacterium tuberculosis
rifampin-resistant strains have been associated with mutations in an 81-bp rifampin resistance-determining region (RRDR) in the gene
rpoB
. However, if this region alone were targeted, rifampin-resistant strains with mutations outside the RRDR would not be detected. In this study, among 51 rifampin-resistant clinical isolates analyzed by sequencing 1,681-bp-long DNA fragments containing the RRDR, 47 isolates contained mutations within the RRDR, three isolates contained mutations both within and outside the RRDR, and only one isolate had a single missense mutation (Arg548His) located outside the RRDR. A drug susceptibility test of recombinant
Mycobacterium smegmatis
and
M. tuberculosis
isolates carrying mutated
rpoB
(Arg548His) showed an increased MIC for rifampin compared to that of the control strains. Modeling of the Arg548His mutant RpoB-DNA complex revealed that the His548 side chain formed a more stable hydrogen bond structure than did Arg548, reducing the flexibility of the rifampin-resistant cluster II region of RpoB, suggesting that the RpoB Arg548His mutant does not effectively interact with rifampin and results in bacterial resistance to the drug. This is the first report on the relationship between the mutation in codon 548 of RpoB and rifampin resistance in tuberculosis. The novel mutational profile of the
rpoB
gene described here will contribute to the comprehensive understanding of rifampin resistance patterns and to the development of a useful tool for simple and rapid drug susceptibility tests.
Involvement of Holliday Junction Resolvase in Fluoroquinolone-Mediated Killing of Mycobacterium smegmatis
Authors: Long Quanxin , Du Qinglin , Fu Tiwei , Drlica Karl , Zhao Xilin , Xie Jianping
Published: December 2014

The absence of the Holliday-junction Ruv resolvase of
Mycobacterium smegmatis
increased the bacteriostatic and bactericidal activities of the fluoroquinolone moxifloxacin, an important antituberculosis agent. The treatment of
ruvAB
-deficient cells with thiourea and 2,2′-bipyridyl lowered moxifloxacin lethality to wild-type levels, indicating that the absence of
ruvAB
stimulates a lethal pathway involving reactive oxygen species. A hexapeptide that traps the Holliday junction substrate of RuvAB potentiated moxifloxacin-mediated lethality, supporting the development of small-molecule enhancers for moxifloxacin activity against mycobacteria.
Dynamics and Establishment of Clostridium difficile Infection in the Murine Gastrointestinal Tract
Authors: Koenigsknecht Mark J. , Theriot Casey M. , Bergin Ingrid L. , Schumacher Cassie A. , Schloss Patrick D. , Young Vincent B.
Published: December 2014

Clostridium difficile
infection (CDI) following antibiotic therapy is a major public health threat. While antibiotic disruption of the indigenous microbiota underlies the majority of cases of CDI, the early dynamics of infection in the disturbed intestinal ecosystem are poorly characterized. This study defines the dynamics of infection with
C. difficile
strain VPI 10463 throughout the gastrointestinal (GI) tract using a murine model of infection. After inducing susceptibility to
C. difficile
colonization via antibiotic administration, we followed the dynamics of spore germination, colonization, sporulation, toxin activity, and disease progression throughout the GI tract.
C. difficile
spores were able to germinate within 6 h postchallenge, resulting in the establishment of vegetative bacteria in the distal GI tract. Spores and cytotoxin activity were detected by 24 h postchallenge, and histopathologic colitis developed by 30 h. Within 36 h, all infected mice succumbed to infection. We correlated the establishment of infection with changes in the microbiota and bile acid profile of the small and large intestines. Antibiotic administration resulted in significant changes to the microbiota in the small and large intestines, as well as a significant shift in the abundance of primary and secondary bile acids.
Ex vivo
analysis suggested the small intestine as the site of spore germination. This study provides an integrated understanding of the timing and location of the events surrounding
C. difficile
colonization and identifies potential targets for the development of new therapeutic strategies.
AterDDomain-Encoding Gene (SCO2368) Is Involved in Calcium Homeostasis and Participates in Calcium Regulation of a DosR-Like Regulon in Streptomyces coelicolor
Authors: Daigle François , Lerat Sylvain , Bucca Giselda , Sanssouci Édith , Smith Colin P. , Malouin François , Beaulieu Carole
Published: December 2014

AlthoughStreptomyces coelicoloris not resistant to tellurite, it possesses several TerD domain-encoding (tdd) genes of unknown function. To elucidate the function oftdd8, the transcriptomes ofS. coelicolorstrain M145 and of atdd8deletion mutant derivative (the Δtdd8strain) were compared. Several orthologs ofMycobacterium tuberculosisgenes involved in dormancy survival were upregulated in the deletion mutant at the visual onset of prodiginine production. These genes are organized in a putative redox stress response cluster comprising two large loci. A binding motif similar to the dormancy survival regulator (DosR) binding site ofM. tuberculosishas been identified in the upstream sequences of most genes in these loci. A predicted role for these genes in the redox stress response is supported by the low NAD+/NADH ratio in the Δtdd8strain. ThisS. coelicolorgene cluster was shown to be induced by hypoxia and NO stress. While thetdd8deletion mutant (the Δtdd8strain) was unable to maintain calcium homeostasis in a calcium-depleted medium, the addition of Ca2+in Δtdd8culture medium reduced the expression of several genes of the redox stress response cluster. The results shown in this work are consistent with Tdd8 playing a significant role in calcium homeostasis and redox stress adaptation.
A ‘silent’, new polymorphism of factor H and apparent de novo atypical haemolytic uraemic syndrome after kidney transplantation
Authors: Broeders Emine N , Stordeur Patrick , Rorive Sandrine , Dahan Karin
Published: December 2014

The pathophysiology of atypical haemolytic-uraemic syndrome (aHUS) occurring de novo after renal transplantation may include genetic mutations of regulators of complement activation, but they are still rarely determined. A 41-year-old female renal transplant recipient presented two very different episodes of thrombotic microangiopathy. The first episode was associated with antibody-mediated rejection and the second was an isolated, acute aHUS, successfully treated with eculizumab. The diagnosis included a genetic analysis and we found a synonymous variant in the Complement Factor H (CFH) gene, c2634C>T (p.His878=) and low factor H (FH) activity during both events. In conclusion, the diagnosis of aHUS should be considered when TMA is associated with an AMR episode. In this setting, a silent polymorphism of factor H may be responsible for these rare cases of “de novo” aHUS after transplantation.
Birth weight and childhood wheezing disorders: a systematic review and meta-analysis
Authors: Mebrahtu Teumzghi F , Feltbower Richard G , Greenwood Darren C , Parslow Roger C
Published: December 2014

Background

Previous observational studies have claimed that birth weight and childhood wheezing disorders are associated although the results remained inconsistent. One systematic review and two systematic reviews that included meta-analyses reported inconsistent results. We aimed to conduct a systematic review and meta-analysis to investigate this.

Methods

An online search of published papers linking childhood asthma and wheezing disorders with birth weight up to February 2014 was carried out using EMBASE and Medline medical research databases. Summary ORs were estimated using random-effects models. Subgroup meta-analyses were performed to assess the robustness of risk associations and between-study heterogeneity.

Results

A total of 37 studies comprising 1 712 737 participants were included in our meta-analysis. The unadjusted summary ORs for risk of childhood wheezing disorders associated with low birth weight (<2.5 kg) were 1.60 (95% CI 1.39 to 1.85, p<0.001) and 1.37 (95% CI 1.05 to 1.79, p=0.02) when compared with ≥2.5 and 2.5–4.0 kg birthweight groups, respectively. The overall summary OR for high birth weight (>4 kg) as compared to the 2.5–4.0 kg birthweight group was 1.02 (95% CI 0.99 to 1.04, p=0.13). There was substantial heterogeneity in the unadjusted low birth weight risk estimates which was not accounted for by predefined study characteristics. There was no significant heterogeneity in the high birth weight risk estimates. There was some evidence of funnel plot asymmetry and small study effects in the low birth weight (2.5 vs ≥2.5 kg and <2.5 vs 2.5–4 kg) OR estimates.

Conclusions

Our results suggest that low birth (<2.5 kg) is an independent risk factor for wheezing disorders during childhood and adolescence although there was substantial heterogeneity among the risk estimates. However, we found no significant association of high birth weight with wheezing disorders.
Freedom from frozen: the first British military use of lyophilised plasma in forward resuscitation
Authors: Gokhale S G , Scorer Thomas , Doughty H
Published: December 2014

Prehospital use of blood products may improve survival. However, transfusion support with frozen blood components is logistically burdensome and constrains the configuration of prehospital medical support. Alternatives to frozen plasma, including lyophilised plasma, offer the potential for advanced resuscitation in the prehospital environment. We describe the successful use of lyophilised plasma by a UK patrol in the prehospital environment during operations in Afghanistan in 2012 and reflect on recent military experience and the need for further developments.
Is 6-month GRACE risk score a useful tool to predict stroke after an acute coronary syndrome?
Authors: Álvarez-Álvarez Belén , Raposeiras-Roubín Sergio , Abu-Assi Emad , Cambeiro-González Cristina , Gestal-Romaní Santiago , López-López Andrea , Bouzas-Cruz Noelia , Castiñeira-Busto María , Saidhodjayeva Ozoda , Redondo-Diéguez Alfredo , Pereira López Eva , García-Acuña José María , González-Juanatey José Ramón
Published: December 2014

Objectives

The risk of stroke after an acute coronary syndrome (ACS) has increased. The aim of this study was to do a comparative validation of the 6-month GRACE (Global Registry of Acute Coronary Events) risk score and CH2DS2VASc risk score to predict the risk of post-ACS ischaemic stroke.

Methods

This was a retrospective study carried out in a single centre with 4229 patients with ACS discharged between 2004 and 2010 (66.9±12.8 years, 27.9% women, 64.2% underwent percutaneous coronary intervention). The primary end point is the occurrence of an ischaemic stroke during follow-up (median 4.6 years, IQR 2.7–7.1 years).

Results

184 (4.4%) patients developed an ischaemic stroke; 153 (83.2%) had sinus rhythm and 31 (16.9%) had atrial fibrillation. Patients with stroke were older, with higher rates of hypertension, diabetes, previous stroke and previous coronary artery disease. The HR for CHA2DS2VASc was 1.36 (95% CI, 1.27 to 1.48, p<0.001) and for GRACE, HR was 1.02(95% CI, 1.01 to 1.03, p<0.001). Both risk scores show adequate discriminative ability (c-index 0.63±0.02 and 0.60±0.02 for CHA2DS2VASc and GRACE, respectively). In the reclassification method there was no difference (Net Reclassification Improvement 1.98%, p=0.69). Comparing moderate-risk/high-risk patients with low-risk patients, both risk scores showed very high negative predictive value (98.5% for CHA2DS2VASc, 98.1% for GRACE). The sensitivity of CHA2DS2VASc score was higher than the GRACE risk score (95.1% vs 87.0%), whereas specificity was lower (14.4% vs 30.2%).

Conclusions

The 6-month GRACE model is a clinical risk score that facilitates the identification of individual patients who are at high risk of ischaemic stroke after ACS discharge.
Gender-related associations of genetic polymorphisms of α-adrenergic receptors, endothelial nitric oxide synthase and bradykinin B2 receptor with treadmill exercise test responses
Authors: Nunes Rafael Amorim Belo , Barroso Lúcia Pereira , Pereira Alexandre da Costa , Krieger José Eduardo , Mansur Alfredo José
Published: December 2014

Background

Treadmill exercise test responses have been associated with cardiovascular prognosis in individuals without overt heart disease. Neurohumoral and nitric oxide responses may influence cardiovascular performance during exercise testing. Therefore, we evaluated associations between functional genetic polymorphisms of α-adrenergic receptors, endothelial nitric oxide synthase, bradykinin receptor B2 and treadmill exercise test responses in men and women without overt heart disease.

Methods

We enrolled 766 (417 women; 349 men) individuals without established heart disease from a check-up programme at the Heart Institute, University of São Paulo Medical School. Exercise capacity, chronotropic reserve, maximum heart-rate achieved, heart-rate recovery, exercise systolic blood pressure (SBP), exercise diastolic blood pressure (DBP) and SBP recovery were assessed during exercise testing. Genotypes for the α-adrenergic receptors ADRA1A Arg347Cys (rs1048101), ADRA2A 1780 C>T (rs553668), ADRA2B Del 301–303 (rs28365031), endothelial nitric synthase (eNOS) 786 T>C (rs2070744), eNOS Glu298Asp (rs1799983) and BK2R (rs5810761) polymorphisms were assessed by PCR and high-resolution melting analysis.

Results

Maximum SBP was associated with ADRA1A rs1048101 (p=0.008) and BK2R rs5810761 (p=0.008) polymorphisms in men and ADRA2A rs553668 (p=0.008) and ADRA2B rs28365031 (p=0.022) in women. Maximum DBP pressure was associated with ADRA2A rs553668 (p=0.002) and eNOS rs1799983 (p=0.015) polymorphisms in women. Exercise capacity was associated with eNOS rs2070744 polymorphisms in women (p=0.01) and with eNOS rs1799983 in men and women (p=0.038 and p=0.024).

Conclusions

The findings suggest that genetic variants of α-adrenergic receptors and bradykinin B2 receptor may be involved with blood pressure responses during exercise tests. Genetic variants of endothelial nitric oxide synthase may be involved with exercise capacity and blood pressure responses during exercise tests. These responses may be gender-related.
The features of infrared spectrum of bio-polymer and its theoretical investigation
Authors: Pang Xiao-Feng
Published: December 2014

We have here an insight into the features of molecular structures of bio-polymers with α-helix structure using infrared spectrum and elucidated theoretically, its relationship with bio-functions. In this case, we analyzed first the features of molecular structure of collagen and collected further the infrared spectrum of absorption of collagen and bovine serum albumin containing α-helix conformation in 400–4000 cm-1 as well as their changes of strength of infrared absorption with varying temperatures using Fourier Transform–Infrared (FT-IR) spectrometers in the region of 15–95°C. The results show that there is a new band of 1650 cm-1 close to the amide-I band of 1666 cm-1 or 1670 cm-1 in these bio-polymers, its strength decreases exponentially with increasing temperature of the systems, which can be expressed by exp [-(0.437 + 8.987 × 10-6  T 2)], but 1666 cm-1 band increases linearly with increasing temperature. We calculated the energy spectrum of the protein molecules with α-helix conformation using the Soliton Theory of bio-energy transport, which are basically same with the experimental results measured by us. From these results and soliton theory we can conclude that the nonlinear soliton excitation, corresponding to 1650 cm-1 band and the exciton excitation, is related to 1666 cm-1 band, exists in the collagen and bovine serum albumin. In the meanwhile, these results also verified that the soliton theory of bio-energy transport along α-helix bio-polymers is appropriate to the protein molecules with α-helix conformation. Therefore, the studied results are helpful to elucidate the relationship between the molecular structure and bio-function of these bio-polymers.
Characterizing the Haldane phase in quasi-one-dimensional spin-1 Heisenberg antiferromagnets
Authors: Wierschem Keola , Sengupta Pinaki
Published: December 2014

We review the basic properties of the Haldane phase in spin-1 Heisenberg antiferromagnetic chains, including its persistence in quasi-one-dimensional (Q1D) geometries. Using large-scale numerical simulations, we map out the phase diagram for a realistic model applicable to experimental Haldane compounds. We also investigate the effect of different chain coupling geometries and confirm a general mean-field universality of the critical coupling times the coordination number of the lattice. Inspired by recent developments in the characterization of symmetry protected topological (SPT) states, of which the Haldane phase of the spin-1 Heisenberg antiferromagnetic chain is a preeminent example, we provide direct evidence that the Q1D Haldane phase is indeed a nontrivial SPT state.