bluuebunny/crossref_metadata_2025 huggingface dataset:
Large Eddy Simulation of a Turbulent Swirling Jet-A1 Spray Flame Incorporating Chemical Non-Equilibrium Effects Through the Flamelet Model
Authors: Fossi Alain , deChamplain Alain , Ghazlani Ali , Paquet Bernard , Kalla Smail , Bergthorson Jeffrey M. , Akih-Kumgeh Benjamin
Published: September 2014

A large eddy simulation (LES) of a turbulent swirl stabilized jet-A1 flame is presented. The scope of the study is to incorporate a reduced chemistry model, as well as, coupling the turbulent flow characteristics to the chemical reactions and at the same time model the local chemical non-equilibrium due to the turbulent strain. Standard Eulerian and Lagrangian approaches are used to describe both gas and liquid phases, respectively. A joint presumed probability density function (PDF) is used to model turbulent-chemistry interactions in swirling jet-A1 spray flames. A one-component fuel, n-decane, is used as a surrogate for jet-A1. The combustion chemistry of the one component is represented through a reduced chemical kinetic mechanism (CKM) which comprises 139 species and 1 045 reactions, derived from the detailed jet fuel surrogate model, JetSurf 2.0. Numerical results of the gas velocity, the gas temperature and the species mole fractions are compared with a set of published experimental data of a steady flame. In addition to the overall reasonable agreement obtained with the experimental data, it is observed that, by combining a sufficiently realistic chemistry model with LES to simulate a jet-A1 spray flame, the prediction of major species is significantly improved while pollutants such as carbon monoxide (CO) and other species involved in slow reactions, are under predicted for reasons discussed in the paper.
Scaling Considerations for SCO2 Cycle Heat Exchangers
Authors: Carlson Matt , Conboy Thomas , Fleming Darryn , Pasch Jim
Published: September 2014

Many SCO2 Brayton cycle demonstration loops have been constructed or are being planned at various thermal power levels between several kilowatts up to 50MW. However experiences at Sandia National Labs and other organizations have demonstrated that few options exist to procure off-the-shelf heat exchangers, especially for higher temperature ranges, due to high operating and differential pressures and the cost of materials with sufficient strength above 600 °C. This paper reviews fundamental mechanical scaling considerations governing SCO2 cycle heat exchangers that should be considered when designing and constructing SCO2 cycles. Current manufacturing limitations will also be reviewed.
Film Cooling Hole Shape Optimization Using Proper Orthogonal Decomposition
Authors: Nita Kozo , Okita Yoji , Nakamata Chiyuki , Kubo Seiji , Yonekura Kazuo , Watanabe Osamu
Published: September 2014

Film cooling is a very effective cooling method for protecting the turbine blades exposed to hot gas from the heat. Since its cooling effectiveness is highly dependent on the shape of the hole, a wide variety of concepts and design parameters regarding hole shapes have been researched. However, there are no well-defined ways to determine the optimum shape of a film cooling hole.

The CFD is a powerful tool for film cooling hole optimization. But with the number of parameters that define the film cooling hole shapes being so numerous, analytical optimization with CFD often requires computational resources that are unrealistic for the average design environment. Accordingly, for CFD to be effective in the optimization process, it is necessary to reduce the number of computations or shorten the calculation time per computation.

In order to solve this problem, this paper presents a novel approach of applying 3D-POD (3D-Proper Orthogonal Decomposition) to the optimization of film cooling holes. POD is one of the most important component analysis methods and has the potential to reduce the number of parameters.

From the computation results, a solution group was made by the RSM (Response Surface Method) and assessment functions, i.e., film cooling effectiveness, heat transfer coefficient, mixing loss, concentration of stress and robustness were considered first. In the end, however, considering the sensitivity of each objective function, the optimal hole shapes were obtained with only the film effectiveness being evaluated.

In the following sections, this method and its results are described in detail.
Laminar Flamelet Based NOx Predictions for Gas Turbine Combustors
Authors: Sripathi Mohan , Krishnaswami Sundar , Danis Allen M. , Hsieh Shih-Yang
Published: September 2014

Stringent emissions regulations have led engine manufacturers to focus on fuel-efficient low emission technologies. Basic understanding and modeling of fundamental mechanisms governing formation and destruction of NOx, CO and UHC is essential to reduce pollutant emissions. Recent advances in turbulent combustion modeling have enabled designers to use CFD as a design tool for evaluating low emission concepts at the conceptual design phase.

Prediction of pollutant NOx for gas turbine combustors has proven successful for design validation applications. The challenge is to provide quick and accurate estimates of NOx for application to gas turbine combustor preliminary design phase, which can be characterized by multiple design changes, varying operating conditions and a variety of fuel staging concepts. NOx formation processes are typically slow compared to the fast hydrocarbon oxidation reactions. As a result, NOx predictions are typically performed as a post-processing step on thermal field obtained from reacting flow simulations. This work builds on prior work on flamelet approach [1,3] by suitably blending it with FLUENT®’s species transport. NOx production within gas turbine combustors has contributions from two major sources: flame front & post-flame thermal NO. The flame front contributions are obtained from flamelet based computations involving detailed chemistry whereas the slow evolution of post-flame NOx is tracked by explicitly solving for NO species transport. The closure of turbulence-chemistry-interactions is derived from Girimaji’s [2] assumed PDF closure using temperature-composition correlations. A Gaussian PDF shape is used with mean and variance of temperatures accounting for the first and second moments, required for PDF weighting computations. The formulation has been validated against SANDIA D flame, and then extended to GE Aviation’s fielded combustors over a wide range of operating conditions, with errors within 11% at Take-Off condition. The model has also been used for pre-test predictions on a number of combustors under development.
IDDES Study of the Shock Induced Flow Separation in a Transonic Compressor Rotor at Near Stall Condition
Authors: Shi Ke , Fu Song , Morris Scott C.
Published: September 2014

The IDDES (Improved Delayed Detached Eddy Simulation) method was applied to simulate the highly unsteady flow in a transonic compressor at near-stall operating condition. Shock induced separated flow on the casing wall in front of the blade leading edge and the flow separation induced by the shock impinging on the blade suction surface were investigated in detail with the help of IDDES.

The 3D separation in the corner of blade suction side surface and the casing wall in the front portion of the blade was shown to be a vortex-like separation spiraling out from the blade suction surface, connecting to the blade suction wall and the casing wall. Blade tip leakage flow also contributed to the formation of the separation vortex. At near stall condition, shock wave was pushed forward out of the blade passage. The upstream propagation of the separation vortex and the related high entropy region were considered to be a characteristic phenomenon of the flow at near stall condition in this transonic compressor rotor.

The results of the present study explain the origin and the formation of the high entropy region in a transonic compressor rotor near the blade leading edge, which can be closely related to the spike type stall inception observed by other researchers in the transonic case.
Measurements of the 3D Flow Field Downstream of an Aircraft Engine Fan
Authors: Hönen Herwart T. , Werner-Spatz Christian , Giebmanns Angela , Döbbener Guido , Jeschke Peter
Published: September 2014

Flow field measurements have been performed in a jet engine fan. As a part of a sensitivity study on the influence of geometry changes on the performance of the compressor the experiments provide a data base for the verification of extensive numerical simulations covering the fan blades. These investigations help to improve the understanding of how changes in component geometry due to wear affect the engine.

The experimental investigations were carried out down-stream of the fan of a jet engine on the test cell at Lufthansa Technik AG.

The main focus of the measurements was to provide highly resolved flow field data downstream of the OGV. A pneumatic five-hole probe was applied in order to obtain 3D information of the flow properties. In order to detect and to resolve the wakes of the OGVs and of the midspan shrouds of the rotor blades the measurements had to be performed along the blade height and had to cover more than one OGV spacing. Therefore, it was necessary to position the probe at various radial and circumferential locations. The radial positioning of the probe was performed by a standard traversing unit. The different circumferential locations were achieved by a specially developed traversing mechanism on a modified engine fan case, which allowed a continuous positioning in the range of two OGV spacings.

The experiments were carried out for two different operating points of the jet engine. For each of these operating points, the engine was operated with nominal and with increased tip clearance above the fan rotor in order to simulate different wear conditions.

The paper explains the necessary modifications to the jet engine and the set up for the experiments. Furthermore, measured results are shown and compared to the results derived from the CFD simulations which were performed prior to the experimental investigations.
Rotordynamic Behavior of 225 kW (300 HP) Class PMS Motor-Generator System Supported by Gas Foil Bearings
Authors: Choe Bok Seong , Kim Tae Ho , Kim Chang Ho , Lee Yong Bok
Published: September 2014

This paper presents the dynamic behavior of a 225 kW class (300 HP), 60,000 rpm, permanent magnet synchronous (PMS) motor-generator system supported on gas foil bearings (GFBs). The rotor of a 225 kW PMS motor is supported by two identical gas foil journal bearings (GFJBs) and one pair of gas foil thrust bearings (GFTBs). The total weight and axial length of the coupled rotors are 272 N and 1,042 mm, respectively. During the speed-up test to 60,000 rpm, unexpected large subsynchronous rotor motions appear at around 120–130 Hz above 35,040 rpm. After disassembling the motor, an inspection of the top foils of the GFJBs reveals significant rotor rubbing. Thus, the GFJBs are redesigned to have a smaller load capacity by reducing their axial length to 45 mm. In addition, three 50 μm thick shims are installed in the GFJBs at 120° intervals for reducing the swirl speed of air and producing bearing preloads. The modification delays the onset speed of subsynchronous motions to 43,200 rpm and decreases the amplitude of the subsynchronous motions from 20 to 15 μm. These results indicate that the modification improves the stability margin of the high-speed rotor system with increasing stiffness and damping. In addition, the logarithmic decrement trends are in good agreement with the test results.
Risk Based Assessment of Gas Turbines in Pipeline Service
Authors: Thorp Joseph , Khan Faisal , Brun Klaus , Strobel Mike , Khalifa Mohamed
Published: September 2014

This work covers risk based methodologies that are applied to aging gas turbines operating along a pipeline. Data from three decades of operation are presented within the framework of qualitative, semi quantitative and quantitative assessments of operational risk. A detailed RAM simulation model is developed to assess the performance of the pipeline using historical failure and repair data. The total risk is estimated within a fully quantitative model considering replacement cost, repair cost, operation cost, risk of failure and remaining value after a specified period of time. The presented risk assessment methods are shown to be very effective tools in making repair vs. replacement decisions and in evaluating remaining useful life.
Plant Performance Monitoring and Diagnostics: Remote, Real-Time and Automation
Authors: Jiang Xiaomo , Foster Craig
Published: September 2014

Combined cycle gas turbine plants are built and operated with higher availability, reliability, and performance than simple cycle in order to help provide the customer with capabilities to generate operating revenues and reduce fuel costs while enhancing dispatch competitiveness. The availability of a power plant can be improved by increasing the reliability of individual assets through maintenance enhancement and performance degradation recovery through remote efficiency monitoring to provide timely corrective recommendations. This paper presents a comprehensive system and methodology to pursue this purpose by using instrumented data to automate performance modeling for real-time monitoring and anomaly detection of combined cycle gas turbine power plants. Through thermodynamic performance modeling of main assets in a power plant such as gas turbines, steam turbines, heat recovery steam generators, condensers and other auxiliaries, the system provides an intelligent platform and methodology to drive customer-specific, asset-driven performance improvements, mitigate outage risks, rationalize operational patterns, and enhance maintenance schedules and service offerings at total plant level via taking appropriate proactive actions. In addition, the paper presents the components in the automated remote monitoring system, including data instrumentation, performance modeling methodology, operational anomaly detection, and component-based degradation assessment. As demonstrated in two examples, this remote performance monitoring of a combined cycle power plant aims to improve equipment efficiency by converting data into knowledge and solutions in order to drive values for customers including shortening outage downtime, lowering operating fuel cost and increasing customer power sales and life cycle value of the power plant.
An Analytical Stress-Strain Hysteresis Model for a Directionally-Solidified Superalloy Under Thermomechanical Fatigue
Authors: Bouchenot Thomas , Gordon Ali P. , Shinde Sachin , Gravett Phillip
Published: September 2014

Cyclic plasticity and creep are the primary design considerations of 1st and 2nd stage gas turbine blades. Directionally-solidified (DS) Ni-base materials have been developed to provide (1) greater creep ductility and (2) lower minimum creep rate in solidification direction compared to other directions. Tracking the evolution of deformation in DS structures necessitates a constitutive model having the functionality to capture rate-, temperature-, history-, and orientation-dependence. Historically, models rooted in microstructurally-based viscoplasticity simulate the response of long-crystal, dual-phase Ni-base superalloys with extraordinary fidelity; however, a macroscopic approach having reduced order is leveraged to simulate LCF, creep, and creep-fatigue responses with equally high accuracy. This study applies uncoupled creep and plasticity models to predict the TMF of a generic DS Ni-base, and an anisotropic yield theory accounts for transversely-isotropic strength. Due to the fully analytic determination of material constants from mechanical test data, the model can be readily tuned for materials in either peak- or base-loaded units. Application of the model via a parametric study reveals trends in the stabilized hysteresis response of under isothermal fatigue, creep-fatigue, thermomechanical fatigue, and conditions representative of in-service components. Though frequently considered in design and maintenance of turbine materials, non-isothermal fatigue has yet to be accurately predicted for a generalized set of loading conditions. The formulations presented in this study address this knowledge gap using extensions of traditional power law constitutive models.
Generic Design Methodology for Electro-Hydraulic Servo Actuator in Aero-Engine Main Fuel Control System
Authors: Wang Huawei , Wang Xi , Dang Wei , Yao Huating , Wang Bin
Published: September 2014

Focusing on the problem that the high stable quality and excellent servo performance of electrohydraulic actuator are needed in aero-engine control system, this paper aims to propose a complete design method for electrohydraulic servo actuator. Firstly, the static characteristics of mechanical-hydraulic system including solenoid control valve, slave valve and metering valve was analyzed to identify their main structure parameters. Secondly, a nonlinear model of this open-loop mechanical-hydraulic system was established in the framework of AMESim. Thirdly, the model’s transfer function was obtained through Prediction Error Methods (PEM) in system identification. Based on the above work, given that the saturation of duty ratio is a nonlinear link, an integral-separated PI controller was applied to constitute the closed-loop electrohydraulic servo actuator. Moreover, to get optimal performance, the controller parameters design was transferred into an optimization process using Differential Evolution (DE) algorithm. Simulation results illustrated that the designed closed-loop electrohydraulic servo actuator shows rapid servo tracking performance, small overshoot and low power loss. It is consistent with the actual engineering and can be used in most aero-engines. In addition, the entire design methodology is generic and can be transplanted in other actuators design.
Performance and Emissions of a Micro-Turbine Fueled With JP8-Canola Biodiesel Mixtures
Authors: Dülger Zafer , Aslan Samet , Arıcı Müslüm , Catori Coşku , Karabay Hasan , Polat Nur , Akşit İzzet Murat , Saraç Halil İbrahim , Gökalp Burak
Published: September 2014

In this study, a micro gas turbine was operated with JP8 and canola biodiesel blends. The blends tested were JP8, 40% of biodiesel, 60% of biodiesel, and 80% of biodiesel by volume. The turbine was run at 3 speeds, 60.000, 80.000 and 105.000 rpm. Engine power generation and emissions performance were determined. The results reveal that as biodiesel content in the fuel mixture increased, the fuel flow rate increased to maintain the constant speed operation and equivalence ratio reduced. It was shown that TJ35 engine can operate with biodiesel blends in JP8 without sacrificing thrust. In fact, 80% biodiesel blend increased the thrust at 105.000 rpm by 2% compared to JP8. Exhaust gas temperatures slightly reduced with increasing biodiesel content. Higher biodiesel blends resulted in higher CO2, CO and CxHy emissions while O2 emissions reduced. This study demonstrates that a micro gas turbine engine could be operated successfully with JP8-canola biodiesel blends, which means the engine could be utilized in distributed and remote off-grid locations for power generation by burning renewable biodiesel fuels.
Metabolic control of cell death
Authors: Green Douglas R. , Galluzzi Lorenzo , Kroemer Guido
Published: September 2014

Beyond their contribution to basic metabolism, the major cellular organelles, in particular mitochondria, can determine whether cells respond to stress in an adaptive or suicidal manner. Thus, mitochondria can continuously adapt their shape to changing bioenergetic demands as they are subjected to quality control by autophagy, or they can undergo a lethal permeabilization process that initiates apoptosis. Along similar lines, multiple proteins involved in metabolic circuitries, including oxidative phosphorylation and transport of metabolites across membranes, may participate in the regulated or catastrophic dismantling of organelles. Many factors that were initially characterized as cell death regulators are now known to physically or functionally interact with metabolic enzymes. Thus, several metabolic cues regulate the propensity of cells to activate self-destructive programs, in part by acting on nutrient sensors. This suggests the existence of “metabolic checkpoints” that dictate cell fate in response to metabolic fluctuations. Here, we discuss recent insights into the intersection between metabolism and cell death regulation that have major implications for the comprehension and manipulation of unwarranted cell loss.
DOK7
gene therapy benefits mouse models of diseases characterized by defects in the neuromuscular junction
Authors: Arimura Sumimasa , Okada Takashi , Tezuka Tohru , Chiyo Tomoko , Kasahara Yuko , Yoshimura Toshiro , Motomura Masakatsu , Yoshida Nobuaki , Beeson David , Takeda Shin’ichi , Yamanashi Yuji
Published: September 2014

Building connections by gene therapy

Voluntary movement requires a molecular conversation between nerves and muscles. This conversation occurs at the neuromuscular junction, a structure where nerves and muscle physically connect. People with diseases characterized by muscle weakness have aberrantly small neuromuscular junctions. Arimura
et al.
used gene therapy to enlarge the neuromuscular junction, which made muscles stronger. Studying mouse models of two distinct neuromuscular disorders, they used an adenovirus vector to deliver
DOK7
, a gene required for formation of the neuromuscular junction. The therapy improved the mice's motor activity and life span.

Science
, this issue p.
1505
Six centuries of variability and extremes in a coupled marine-terrestrial ecosystem
Authors: Black Bryan A. , Sydeman William J. , Frank David C. , Griffin Daniel , Stahle David W. , García-Reyes Marisol , Rykaczewski Ryan R. , Bograd Steven J. , Peterson William T.
Published: September 2014

Rings of ocean upwelling

Coastal upwelling along the coast of California has become more variable than during nearly any period in the past 600 years. Black
et al.
used a 576-year tree ring record to construct a record of wintertime climate along the California coast. Because wintertime climate and coastal upwelling are so closely linked there, they were able to determine that upwelling variability has increased more over the past 60 years than for all but two intervals during that time. The apparent causes of the recent trend appear to be unique, resulting in reduced marine productivity and negative impacts on fish, seabirds, and mammals.

Science
, this issue p.
1498
Room-temperature coupling between electrical current and nuclear spins in OLEDs
Authors: Malissa H. , Kavand M. , Waters D. P. , van Schooten K. J. , Burn P. L. , Vardeny Z. V. , Saam B. , Lupton J. M. , Boehme C.
Published: September 2014

Organic semiconductors go out for a spin

Magnetism is a commonly observed phenomenon in the macroscopic world, but its origins lie in the quirky quantum-mechanical property of electrons and certain nuclei known as spin. Recent research has sought to leverage and expand the role of spin in the operation of electronic devices. Malissa
et al.
used a highly sensitive spectroscopic technique to probe, and ultimately manipulate, the subtle effects of spin interactions on the current that flows through organic light-emitting diodes (OLEDs) (see the Perspective by Bobbert). They pinpointed coupling between the spins of the current carriers and the hydrogen nuclei in the hydrocarbon-based material making up the device.

Science
, this issue p.
1487
; see also p.
1450
Cascading into focus
Authors: Zhang Yan , Sontheimer Erik J.
Published: September 2014

Structures of a multisubunit protein-RNA complex reveal how the CRISPR system recognizes DNA targets

[Also see Research Articles by

Jackson
et al.

and

Mulepati
et al.

]
Outsmarting the placebo effect
Authors: Servick Kelly
Published: September 2014

Can a genetic test to predict a person's level of placebo response help new drugs win approval?
Whole-Genome Comparison of Aspergillus fumigatus Strains Serially Isolated from Patients with Aspergillosis
Authors: Hagiwara Daisuke , Takahashi Hiroki , Watanabe Akira , Takahashi-Nakaguchi Azusa , Kawamoto Susumu , Kamei Katsuhiko , Gonoi Tohru
Published: September 2014

The emergence of azole-resistant strains of
Aspergillus fumigatus
during treatment for aspergillosis occurs by a mutation selection process. Understanding how antifungal resistance mechanisms evolve in the host environment during infection is of great clinical importance and biological interest. Here, we used next-generation sequencing (NGS) to identify mutations that arose during infection by
A. fumigatus
strains sequentially isolated from two patients, one with invasive pulmonary aspergillosis (IPA) (five isolations) and the other with aspergilloma (three isolations). The serial isolates had identical microsatellite types, but their growth rates and conidia production levels were dissimilar. A whole-genome comparison showed that three of the five isolates from the IPA patient carried a mutation, while 22 mutations, including six nonsynonymous ones, were found among three isolates from the aspergilloma patient. One aspergilloma isolate carried the
cyp51A
mutation P216L, which is reported to confer azole resistance, and it displayed an MIC indicating resistance to itraconazole. This isolate harbored five other nonsynonymous mutations, some of which were found in the
afyap1
and
aldA
genes. We further identified a large deletion in the aspergilloma isolate in a region containing 11 genes. This finding suggested the possibility that genomic deletions can occur during chronic infection with
A. fumigatus
. Overall, our results revealed dynamic alterations that occur in the
A. fumigatus
genome within its host during infection and treatment.
Group A Escherichia coli-Related Purpura Fulminans: an Unusual Manifestation Due to an Unusual Strain?
Authors: Amara Marlène , Bonacorsi Stéphane , Bedel Jérôme , Mira Jean-Paul , Laurent Virginie , Socha Koryna , Bruneel Fabrice , Pangon Béatrice , Bédos Jean-Pierre , Grimaldi David
Published: September 2014

We describe an exceptional case of life-threatening group A
Escherichia coli
-induced purpura fulminans. Genotyping of common polymorphisms in genes involved in innate immunity or coagulation did not reveal known susceptibility to such a manifestation. Genetic analysis of the strain revealed an unusual conserved virulence plasmidic region, pointing out its potential virulence.
Quantitative Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry for Rapid Resistance Detection
Authors: Lange Christoph , Schubert Sören , Jung Jette , Kostrzewa Markus , Sparbier Katrin
Published: September 2014

Antibiotic resistance in Gram-negative microorganisms is an increasing health care problem. The rapid detection of such resistance is crucial for starting an early specific therapy and to enable initiation of the required hygiene measures. With continued emphasis on reducing the cost of laboratory testing, only economical/low-cost approaches have a chance of being implemented. During recent years, matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) has been developed to be a standard method in microbiology laboratories for the rapid and cost-efficient identification of microorganisms. Extending the usage of MALDI-TOF MS in the clinical microbiology laboratory to the area of resistance testing is an attractive option. Quantitative MALDI-TOF MS using an internal standard facilitates the measurement of the quantity of peptides and small proteins within a spectrum. These quantities correlate to the number of microorganisms and therefore to the growth of a microorganism. The comparison of growth in the presence or absence of an antibiotic allows for analysis of the susceptibility behavior of a strain. Here, we describe a novel method and its application in the analysis of 108
Klebsiella
sp. isolates. After 1 h of incubation at a meropenem concentration of 8 μg/ml, a sensitivity of 97.3% and a specificity of 93.5% were achieved (compared to Etest results).
Evaluation of High-Resolution Melting Curve Analysis of Ligation-Mediated Real-Time PCR, a Rapid Method for Epidemiological Typing of ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter Species) Pathogens
Authors: Woksepp Hanna , Ryberg Anna , Billström Hanna , Hällgren Anita , Nilsson Lennart E. , Marklund Britt-Inger , Olsson-Liljequist Barbro , Schön Thomas
Published: September 2014

A single-tube method, ligation-mediated real-time PCR high-resolution melt analysis (LMqPCR HRMA), was modified for the rapid typing of
Enterococcus faecium
,
Staphylococcus aureus
,
Klebsiella pneumoniae
,
Acinetobacter baumannii
,
Pseudomonas aeruginosa
, and
Enterobacter
spp. (ESKAPE) pathogens. A 97% agreement (60/62 isolates) was achieved in comparison to pulsed-field gel electrophoresis (PFGE) results, which indicates that LMqPCR HRMA is a rapid and accurate screening tool for monitoring nosocomial outbreaks.
Crystal Structure of Herpes Simplex Virus 2 gD Bound to Nectin-1 Reveals a Conserved Mode of Receptor Recognition
Authors: Lu Guangwen , Zhang Na , Qi Jianxun , Li Yan , Chen Zhujun , Zheng Chunfu , Gao George F , Yan Jinghua
Published: September 2014

Herpes simplex virus 1 (HSV-1) and HSV-2 are among the most prevalent human pathogens. Both viruses can recognize, via the surface envelope glycoprotein D (gD), human nectin-1 as a functional receptor. Previous studies have successfully elucidated the molecular basis of the binding between HSV-1 gD and nectin-1 by cocrystallography. Despite a high sequence identity between HSV-1 and HSV-2 gDs, the atomic intermolecule details for the HSV-2-gD/nectin-1 interaction remain elusive. Here, we report the crystal structures of both the unbound and the nectin-1-bound HSV-2 gDs. The free-gD structure expectedly comprises an IgV-like core and the surface-exposed terminal extensions as observed in its HSV-1 counterpart but lacks traceable electron densities for a large portion of the terminal elements. These terminal residues were clearly traced in the complex structure as a definitive loop in the N terminus and an α-helix in the C terminus, thereby showing a conserved nectin-1-binding mode as reported for HSV-1 gD. The interface residues in nectin-1 were further mutated and tested for the gD interaction by surface plasmon resonance. The resultant binding patterns were similar for HSV-1 and HSV-2 gDs, further supporting a homologous receptor-binding basis by the two viruses for nectin-1. These data, together with a cell-based fusion assay showing a cross-inhibition of the gD/nectin-1-mediated cell-cell fusion by soluble HSV-1 and HSV-2 gDs, provided solid structural and functional evidence that HSV-1 and HSV-2 recognize nectin-1 via the same binding mode. Finally, we also demonstrated that nectin-1 I80 is an important residue involved in gD interaction.

IMPORTANCE
Despite intensified studies, a detailed picture of the molecular features in the HSV-2-gD/nectin-1 interaction remains unavailable. Previous work focused on HSV-1 gD, which folds into an IgV-like core with large terminal extensions and utilizes the extension elements to engage nectin-1. Here, we report the crystal structures of HSV-2 gD in both the free and the nectin-1-bound forms. The atomic intermolecule details for HSV-2-gD/nectin-1 interaction are clearly presented. The observed binding mode is identical to that reported for its HSV-1 counterpart. This structural observation was further supported by our comparative functional assays showing that nectin-1 mutations similarly affect the ligand-receptor interaction of both virus gDs. Taken together, we provide comprehensive structural and functional data demonstrating a conserved receptor-binding mode between HSV-1 and HSV-2 for nectin-1. Our results also indicate that the tropism difference between the two viruses likely arises from aspects other than the gD/nectin-1 binding features.
Sendai Virus Pathogenesis in Mice Is Prevented by
Ifit2
and Exacerbated by Interferon
Authors: Wetzel Jaime L. , Fensterl Volker , Sen Ganes C.
Published: September 2014

The type I/III interferon (IFN) system has major roles in regulating viral pathogenesis, usually ameliorating pathogenesis by impairing virus replication through the antiviral actions of one or more IFN-induced proteins. Ifit2 is one such protein which can be induced by IFN or virus infection, and it is responsible for protecting mice from neuropathogenesis caused by vesicular stomatitis virus. Here, we show that Ifit2 also protects mice from pathogenesis caused by the respirovirus Sendai virus (SeV). Mice lacking
Ifit2
(
Ifit2
−/−
) suffered severe weight loss and succumbed to intranasal infection with SeV strain 52 at a dose that killed only a few wild-type mice. Viral RNA was detectable only in lungs, and SeV titers were higher in
Ifit2
−/−
mice than in wild-type mice. Similar infiltration of immune cells was found in the lungs of both mouse lines, corresponding to similar levels of many induced cytokines and chemokines. In contrast, IFN-β and IFN-λ3 expression were considerably higher in the lungs of
Ifit2
−/−
mice. Surprisingly, type I IFN receptor knockout (
IFNAR
−/−
) mice were less susceptible to SeV than
Ifit2
−/−
mice, although their pulmonary virus titers were similarly high. To test the intriguing possibility that type I IFN action enhances pathogenesis in the context of elevated SeV replication in lungs, we generated
Ifit2/IFNAR
−/−
double knockout mice. These mice were less susceptible to SeV than
Ifit2
−/−
mice, although viral titers in their lungs were even higher. Our results indicate that high SeV replication in the lungs of infected
Ifit2
−/−
mice cooperates with elevated IFN-β induction to cause disease.

IMPORTANCE
The IFN system is an innate defense against virus infections. It is triggered quickly in infected cells, which then secrete IFN. Via their cell surface receptors on surrounding cells, they induce transcription of numerous IFN-stimulated genes (ISG), which in turn protect these cells by inhibiting virus life cycles. Hence, IFNs are commonly considered beneficial during virus infections. Here, we report two key findings. First, lack of a single ISG in mice,
Ifit2
, resulted in high mortality after SeV infection of the respiratory tract, following higher virus loads and higher IFN production in
Ifit2
−/−
lungs. Second, mortality of
Ifit2
−/−
mice was reduced when mice also lacked the type I IFN receptor, while SeV loads in lungs still were high. This indicates that type I IFN exacerbates pathogenesis in the SeV model, and that limitation of both viral replication and IFN production is needed for effective prevention of disease.
Commentary: Trunkloads of Viruses
Authors: Pellett Philip E.
Published: September 2014

Elephant populations are under intense pressure internationally from habitat destruction and poaching for ivory and meat. They also face pressure from infectious agents, including elephant endotheliotropic herpesvirus 1 (EEHV1), which kills ∼20% of Asian elephants (
Elephas maximus
) born in zoos and causes disease in the wild. EEHV1 is one of at least six distinct EEHV in a phylogenetic lineage that appears to represent an ancient but newly recognized subfamily (the
Deltaherpesvirinae
) in the family
Herpesviridae
.
Estimating the risk of cardiovascular disease using an obese-years metric
Authors: Abdullah Asnawi , Amin Fauzi Ali , Stoelwinder Johannes , Tanamas Stephanie K , Wolfe Rory , Barendregt Jan , Peeters Anna
Published: September 2014

Objective

To examine the association between obese-years and the risk of cardiovascular disease (CVD).

Study design

Prospective cohort study.

Setting

Boston, USA.

Participants

5036 participants of the Framingham Heart Study were examined.

Methods

Obese-years was calculated by multiplying for each participant the number of body mass index (BMI) units above 29 kg/m2by the number of years lived at that BMI during approximately 50 years of follow-up. The association between obese-years and CVD was analysed using time-dependent Cox regression adjusted for potential confounders and compared with other models using the Akaike information criterion (AIC). The lowest AIC indicated better fit.

Primary outcome

CVD.

Results

The median cumulative obese-years was 24 (range 2–556 obese-years). During 138 918 person-years of follow-up, 2753 (55%) participants were diagnosed with CVD. The incidence rates and adjusted HR (AHR) for CVD increased with an increase in the number of obese-years. AHR for the categories 1–24.9, 25–49.9, 50–74.9 and ≥75 obese-years were, respectively, 1.31 (95% CI 1.15 to 1.48), 1.37 (95% CI 1.14 to 1.65), 1.62 (95% CI 1.32 to 1.99) and 1.80 (95% CI 1.54 to 2.10) compared with those who were never obese (ie, had zero obese-years). The effect of obese-years was stronger in males than females. For every 10 unit increase in obese-years, the AHR of CVD increased by 6% (95% CI 4% to 8%) for males and 3% (95% CI 2% to 4%) for females. The AIC was lowest for the model containing obese-years compared with models containing either the level of BMI or the duration of obesity alone.

Conclusions

This study demonstrates that obese-years metric conceptually captures the cumulative damage of obesity on body systems, and is found to provide slightly more precise estimation of the risk of CVD than the level or duration of obesity alone.
The Improving Rural Cancer Outcomes (IRCO) Trial: a factorial cluster-randomised controlled trial of a complex intervention to reduce time to diagnosis in rural patients with cancer in Western Australia: a study protocol
Authors: Emery Jon D , Gray Victoria , Walter Fiona M , Cheetham Shelley , Croager Emma J , Slevin Terry , Saunders Christobel , Threlfall Tim , Auret Kirsten , Nowak Anna K , Geelhoed Elizabeth , Bulsara Max , Holman C D'Arcy J
Published: September 2014

Introduction

While overall survival for most common cancers in Australia is improving, the rural–urban differential has been widening, with significant excess deaths due to lung, colorectal, breast and prostate cancer in regional Australia. Internationally a major focus on understanding variations in cancer outcomes has been later presentation to healthcare and later diagnosis. Approaches to reducing time to diagnosis of symptomatic cancer include public symptom awareness campaigns and interventions in primary care to improve early cancer detection. This paper reports the protocol of a factorial cluster-randomised trial of community and general practice (GP) level interventions to reduce the time to diagnosis of cancer in rural Western Australia (WA).

Methods and analysis

The community intervention is a symptom awareness campaign tailored for rural Australians delivered through a community engagement model. The GP intervention includes a resource card with symptom risk assessment charts and local referral pathways implemented through multiple academic detailing visits and case studies. Participants are eligible if recently diagnosed with breast, colorectal, lung or prostate cancer who reside in specific regions of rural WA with a planned sample size of 1350. The primary outcome is the Total Diagnostic Interval, defined as the duration from first symptom (or date of cancer screening test) to cancer diagnosis. Secondary outcomes include cancer stage, healthcare utilisation, disease-free status, survival at 2 and 5 years and cost-effectiveness.

Ethics and dissemination

Ethics approval has been granted by the University of Western Australia and from all relevant hospital recruitment sites in WA.

Results

Results of this trial will be reported in peer-reviewed publications and in conference presentations.

Trial registration number

Australian New Zealand Clinical Trials Registry (ANZCTR). ACTRN12610000872033.
Endovascular treatment of acute intracranial vertebral artery dissection: long-term follow-up results of internal trapping and reconstructive treatment using coils and stents
Authors: Nam Kyoung Hyup , Ko Jun Kyeung , Cha Seung Heon , Choi Chang Hwa , Lee Tae Hong , Lee Jae Il
Published: September 2014

Background

Endovascular internal trapping is an effective procedure for the treatment of acute vertebral artery dissection (VAD). However, the outcomes of reconstructive treatment have not been well established. The aim of our study is to evaluate the long-term clinical and angiographic results of endovascular internal trapping or reconstructive treatment of acute VAD.

Methods

Between 2005 and 2013, 26 patients with acute VAD were managed with internal coil trapping (n=10), stent-assisted coiling (n=14), stent only (n=1), and proximal occlusion (n=1). Stent-assisted coiling included the modified stent-assisted semi-jailing technique (n=10), balloon-in-stent technique (n=2), and coiling followed by balloon mounted stent (n=2). Digital subtraction angiography (DSA) was performed in all patients except for three who died during the acute stage.

Results

Of 26 patients with VAD, 14 and 12 presented with hemorrhagic and non-hemorrhagic types, respectively. The dominancy of the relevant artery was defined as dominant (n=9), even (n=12), and non-dominant (n=5). Reconstructive treatment was performed in six patients with ruptured VADs which failed balloon test occlusion and nine with non-hemorrhagic VADs. Clinical outcomes were favorable in 22 (84.6%), severe disability occurred in one, and there were three deaths (11.5%). All patients except the three who died had angiographic follow-up at 6–32 months (mean 10.4 months). The angiographic results of nine cases of internal trapping and one of proximal occlusion all showed a stable occlusion state. Among the 15 cases of reconstructive treatment, follow-up DSAs were available for the 13 surviving patients, 10 of which demonstrated stable occlusion of aneurysmal dilation and patent parent artery.

Conclusions

This study suggests that internal trapping is a stable and effective treatment for acute VAD. Reconstructive treatment using stent and coils could also be a feasible alternative modality for hemorrhagic type VAD. However, serial DSA follow-up is essential.
Medicines residues and quality assurance schemes
Authors: Brigstocke Tim
Published: September 2014

In the second of an occasional series of articles for Veterinary Record produced by the Veterinary Residues Committee, Tim Brigstocke discusses the implications for producers of the finding of non‐compliant medicines residues in their animals
Whey protein supplementation increases methionine intake but not homocysteine plasma concentration in rats
Authors: Deminice Rafael , Comparotto Hugo , Jordao Alceu Afonso
Published: September 2014

The purpose of this study was to examine the effects of whey protein supplementation on homocysteine (Hcy) metabolism and liver oxidative stress in rats. Twenty-four rats were divided into 3 groups (n = 8) to receive one of the following diets for 4 weeks: control diet (C), whey protein-composed diet (WP), and whey protein-supplemented diet (WPS). The C and WP diets consisted of AIN-93 with 20% casein and 20% whey protein as protein source, respectively. WPS was AIN-93 (20% casein) supplemented by the addition of 20% (w/w) whey protein. Four weeks of ingesting a WPS diet resulted in a significantly higher (P < 0.05) total protein and methionine intakes. Although a significant increase (P < 0.05) in the hepatic S-adenosylmethionine and S-adenosylhomocysteine levels occurred in WPS group compared with C and WP, no significant change was observed in plasma Hcy concentration between groups. Furthermore, the levels of lipid hydroperoxides and advanced oxidation protein products, known liver oxidative stress markers, were increased in the WPS group compared with the C group. In addition, no change in glutathione liver concentration was observed in any of the groups studied. In conclusion, whey protein supplementation increases methionine intake substantially; however, it does not change plasma Hcy concentrations. On the other hand, increased hepatic oxidative stress markers were observed in whey protein supplemented rats were probably due to high protein intake.
Experimental framework for evaluating the mechanical behavior of dry and wet crushable granular materials based on the particle breakage ratio
Authors: Ovalle Carlos , Dano Christophe , Hicher Pierre-Yves , Cisternas Mónica
Published: September 2014

It has been widely shown that particle crushing increases the compressibility of granular materials. For a particular crushable material and given test conditions, an empirical relation can be established between the breakage ratio and the plastic work. Along these lines, constitutive models have been developed based on the effect of grading evolution during crushing. In parallel, due to corrosive attacks of the humid environment at the tip of microcracks within solid grains, the mechanical behavior of crushable granular materials depends also on the water content: the higher the material humidity, the higher the particle crushing. However, the experimental data on the relation between loading–wetting conditions and the breakage ratio are still quite scarce. In this paper, we present experimental results on crushable sand to study the effect of flooding under isotropic, oedometric, and triaxial stress paths. The main objective of this study is to obtain a consistent framework for the effect of water based on the breakage ratio. Our results have shown that, for a given initial density and stress path, the dry material after flooding reaches the equivalent behavior of the initially wetted material in terms of compression curve, particle crushing, and creep compressibility index, regardless of the point of flooding. Moreover, the relation between the breakage ratio and the final void ratio is unique and depends neither on the stress path, the water content, the point of flooding, nor the loading condition (time of creep or relaxation), but exclusively on the initial density and on intrinsic parameters. These findings could improve the prediction of the effect of water and time on the mechanical response of crushable granular materials through constitutive models based on grading evolution.
The development of organometallic OBOC peptide libraries and sequencing of N-terminal rhenium(I) tricarbonyl-containing peptides utilizing MALDI tandem mass spectrometry
Authors: Cruickshank Dana R. , Luyt Leonard G.
Published: September 2014

The development of peptide-based imaging agents through screening of large peptide libraries is hindered by the additional requirement of a radionuclide−chelator complex that can negatively affect the binding properties of the peptide. Herein, we report N-terminal rhenium(I)tricarbonyl OBOC (one-bead, one-compound) peptide libraries for use in the direct screening of potential imaging agents. The rhenium(I) tricarbonyl is incorporated directly in the library as an imaging entity surrogate to account for the presence of a technetium-99m radionuclide chelate. The identification of unknown organometallic peptides on single beads is successfully accomplished through MALDI tandem mass spectrometry, preceded by a systematic investigation of the effects of a variety of N-terminal rhenium(I) tricarbonyl chelates on peptide fragmentation patterns.