bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of a 30PS Class Small Gas Turbine and Its Power-Up Version
Authors: Hoshino A. , Sugimoto T. , Tatsumi T. , Nakagawa Y.
Published: October 2009

Due to the recent popularity of small and medium-sized industrial gas turbines in many fields, gas turbines below 100 SHP have been employed as prime movers, a power range traditionally reserved for diesel and gasoline engines. Generally speaking, however, small gas turbines have many design difficulties in thermal efficiency, high rotational speed, compact auxiliary equipment, etc., derived from limitations of their dimensions. Small gas turbines S5A-01 and S5B-01, which have 32 PS output power at standard conditions, have been developed and are being produced. Presently, a 30 percent growth rated power producer for S5A-02 and S5B-02 gas turbines is under development. These engines’ configurations are as follows: single-stage centrifugal compressor; single-stage radial turbine; single can combustor; hybrid fuel nozzle with pressure atomizer and airblast atomizer; fuel control valve with pulse width modulation system; electric motor drive fuel pump. In this paper, the authors describe the design features and development history of the base engine and the experimental results with the growth rated version.
Fault Diagnosis of Gas Turbine Engines From Transient Data
Authors: Merrington G. L.
Published: October 2009

The desirability of being able to extract relevant fault diagnostic information from transient gas turbine data records is discussed. A method is outlined for estimating the effects of unmeasured fault parameters from input/output measurements. The resultant sensitivity of the technique depends on the sampling rate and the measurement noise.
Health Monitoring of Variable Geometry Gas Turbines for the Canadian Navy
Authors: Muir D. E. , Saravanamuttoo H. I. H. , Marshall D. J.
Published: October 2009

The Canadian Department of National Defence has identified a need for improved Engine Health Monitoring procedures for the new Canadian Patrol Frigate (CPF). The CPF propulsion system includes two General Electric LM2500 gas turbines, a high-pressure-ratio engine with multiple stages of compressor variable geometry. A general method for predicting the thermodynamic performance of variable geometry axial compressors has been developed. The new modeling technique is based on a meanline stage-stacking analysis and relies only on the limited performance data typically made available by engine manufacturers. The method has been applied to the LM2500-30 marine gas turbine and the variations in engine performance that can result from a malfunction of the variable geometry system in service have been estimated.
Rolling Element Bearing Monitoring and Diagnostics Techniques
Authors: Harker R. G. , Sandy J. L.
Published: October 2009

Rolling element bearings require distinctly different techniques for monitoring and diagnostics from those used for fluid-film type bearings. A description of these techniques and the instrumentation used to acquire the necessary data is provided for comparison. Also included are some case studies to illustrate how these techniques are applied.
Active Control of Transient Rotordynamic Vibration by Optimal Control Methods
Authors: Palazzolo A. B. , Lin R. R. , Kascak A. F. , Alexander R. M.
Published: October 2009

Although considerable effort has been put into the study of steady-state vibration control, there are few methods applicable to transient vibration control of rotor-bearing systems. In this paper optimal control theory has been adopted to minimize rotor vibration due to sudden imbalance, e.g., blade loss. The system gain matrix is obtained by choosing the weighting matrices and solving the Riccati equation. Control forces are applied to the system via a feedback loop. A seven mass rotor system is simulated for illustration. A relationshp between the number of sensors and the number of modes used in the optimal control model is investigated. Comparisons of responses are made for various configurations of modes, sensors, and actuators. Furthermore, spillover effect is examined by comparing results from collocated and noncollocated sensor configurations. Results show that shaft vibration is significantly attenuated in the closed-loop system.
Fatigue Life Prediction Modeling for Turbine Hot Section Materials
Authors: Halford G. R. , Meyer T. G. , Nelson R. S. , Nissley D. M. , Swanson G. A.
Published: October 2009

This paper presents a summary of the life prediction methods developed under the NASA Lewis Research Center’s Hot Section Technology (HOST) program. A major objective of the fatigue and fracture efforts under the HOST program was to significantly improve the analytic life prediction tools used by the aeronautical gas turbine engine industry. This has been achieved in the areas of high-temperature thermal and mechanical fatigue of bare and coated high-temperature superalloys. Such technical improvements will eventually reduce life cycle costs. The cyclic crack initiation and propagation resistance of nominally isotropic polycrystalline alloys and highly anisotropic single crystal alloys have been addressed. A sizeable data base has been generated for three alloys [cast PWA 1455 (B–1900 + Hf), wrought Inconel 718, and cast single-crystal PWA 1480] in bare and coated conditions. Two coating systems, diffusion aluminide (PWA 273) and plasma-sprayed MCrAlY overlay (PWA 286), were employed. Life prediction modeling efforts were devoted to creep-fatigue interaction, oxidation, coatings interactions, multiaxially of stress-strain states, mean stress effects, cumulative damage, and thermomechanical fatigue. The fatigue crack initiation life models developed to date include the Cyclic Damage Accumulation (CDA) Model of Pratt & Whitney and the Total Strain Version of Strainrange Partitioning (TS-SRP) of NASA Lewis for nominally isotropic materials, and the Tensile Hysteretic Energy Model of Pratt & Whitney for anisotropic superalloys. The fatigue model being developed by the General Electric Company is based upon the concepts of Path-Independent Integrals (PII) for describing cyclic crack growth under complex non-linear response at the crack tip due to thermomechanical loading conditions. A micromechanistic oxidation crack extension model has been derived by researchers at Syracuse University. The models are described and discussed in the paper. Only limited verification has been achieved to date as several of the technical programs are still in progress and the verification tasks are scheduled, quite naturally, near the conclusion of the program. To date, efforts have concentrated on developement of independent models for cyclic constitutive behavior, cyclic crack initiation, and cyclic crack propagation. The transition between crack initiation and crack propagation has not been thoroughly researched as yet, and the integration of these models into a unified life prediction method has not been addressed.
Predicting Gas Turbine Performance Degradation Due to Compressor Fouling Using Computer Simulation Techniques
Authors: Aker G. F. , Saravanamuttoo H. I. H.
Published: October 2009

As part of an ongoing investigation into the effects of compressor fouling on gas turbine performance, the stage stacking technique was used in conjunction with generalized turbine characteristics to simulate the performance of two common pipeline engines, the G. E. LM2500 and the Solar Centaur. A linear fouling model was introduced that simulates the progressive buildup of contaminants in the compressor by modifying the appropriate stage flow and efficiency characteristics in a stepwise fashion. This simulation of the onset and progressive nature of compressor fouling allows quantitative analysis of performance deterioration to be performed on the basis of trends noted in monitored parameters. A preliminary study into how severely a given level of fouling will affect engines of different size indicated that stage loading may be the more critical parameter.
Control Considerations for an On-Line, Active Regeneration System for Diesel Particulate Traps
Authors: Stiglic P. , Hardy J. , Gabelman B.
Published: October 2009

Garrett Automotive Group is developing an exhaust aftertreatment system aimed at particulate emissions reduction from commercial diesel engines. The system uses a ceramic wall flow filter to trap the particulates, and regeneration is effected by raising gas temperature by throttling the exhaust downstream of the turbocharger. Lab testing at steady conditions demonstrated good performance with both catalyzed and uncatalyzed traps. Road testing shows the regeneration must be accomplished under severe transient conditions created by the normal vehicle operating modes. Primary efforts are to accommodate those transients using advanced control and digital computational techniques. Some of those techniques are described and are shown to yield improved control performance.
Spray and Flame Structure in Diesel Combustion
Authors: Balles E. N. , Heywood J. B.
Published: October 2009

The diesel combustion process in direct-injection diesel engines consists of four distinct stages: an ignition delay, a premixed phase, a mixing-controlled phase, and a late combustion phase. This paper uses geometric information from high-speed direct and shadowgraph movies and corresponding combustion chamber pressure histories, taken in a rapid compression machine study of direct-injection diesel combustion, for a coupled analysis of the diesel flame geometry and energy or heat release to develop our understanding of the diesel spray and flame structure during the ignition delay period and premixed combustion phase. It is shown that each fuel spray from a multihole fuel-injector nozzle consists of a narrow liquid-containing core centered within a much larger fuel-vapor air region, which has a distinct boundary. The liquid core does not penetrate to the chamber periphery, while the vapor containing spray interacts strongly with the boundary. Ignition occurs part way along each growing spray. Once combustion starts, the outer boundary of the fuel-vapor-containing region expands more rapidly due to the combustion energy release. Very high initial spreading rates of the luminous region boundary are observed. A comparison of enflamed areas and volumes, and burned gas volumes, indicates that the luminous region during the early stages of combustion (assumed stoichiometric) is around 1 cm thick and does not fill the full height of the chamber. During the premixed combustion phase, the burned gas volume is one-half the enflamed volume, indicating the presence of a substantial unburned (rich) fuel-vapor/air core within the luminous region of each fuel spray. A close correspondence of flame geometry to spray geometry is evident throughout the combustion process.
Progress on the Investigation of Coal-Water-Slurry Fuel Combustion in a Medium-Speed Diesel Engine: Part 3—Accumulator Injector Performance
Authors: Hsu B. D. , Leonard G. L. , Johnson R. N.
Published: October 2009

Coal-water-slurry (CWS) engine tests designed to evaluate a new accumulator-based injection system are described in this paper. The new injection system was found to improve CWS burnout considerably at both full and part engine loads. The peak cylinder firing pressure when operating with CWS was no higher than when operating with diesel oil. These data demonstrate the improved engine performance that can be achieved with the accumulator-based injection system.
Internal Dynamic Force Analysis for V-Type Engine/Compressor With Articulated Power Cylinder Connecting Rod Mechanism
Authors: Doughty S. , Smalley A. J. , Evans B. F.
Published: October 2009

This paper presents a systematic analysis of the internal dynamic forces within a V-engine/compressor with articulated power cylinders. All inertial terms are included in the formulation, which is solvable for the crankshaft torque and all reactions. After formulating the necessary description, the results are applied to two case studies involving pipeline compressor units.
Piston Ring Thermal Transient Effects on Lubricant Temperatures in Advanced Engines
Authors: Boisclair M. E. , Hoult D. P. , Wong V. W.
Published: October 2009

One class of advanced diesel engines operates with low heat rejection and high operating temperatures; piston-ring / liner lubrication is a major problem for these engines. This study attempts to illustrate the time-dependent thermal environment around the top piston ring and lubricant in these advanced engines. Particular emphasis will be placed on the maximum lubricant temperature. The analysis starts with a standard cycle simulation and a global finite-element analysis of the piston and liner in relative motion. A more detailed finite-element model, which considers variable oil film thickness on the liner, focuses on the top ring and lubricant and uses the groove and liner temperatures generated in the global analysis as boundary conditions. Results for different heat rejection engine configurations are presented. We observe that because of major transient effects, high lubricant temperature is experienced not only at top ring reversal but also down the liner to bottom ring reversal.
The Modernization of a 1965 MS5001 Gas Turbine: New Life for an Old Unit
Authors: Grondahl C. M. , Linnell R. D. , Martin T. J.
Published: October 2009

Application of the GE MS5001 gas turbine performance improvement uprate package has been extended to an early model “K” unit at Texaco’s Convent, LA, refinery. This extensive modification required replacement of the turbine shell in addition to the installation of new technology components developed for more recent MS5001 models. This paper presents the customer’s motivation to refurbish a 22-year-old gas turbine. Gas turbine component design improvements and interfaces are discussed with performance and reliability gains. Field service engineering experience installing the uprate is also related.
The Prediction and Measurement of Incompressible Flow in a Labyrinth Seal
Authors: Demko J. A. , Morrison G. L. , Rhode D. L.
Published: October 2009

Predictions and measurements were obtained for incompressible flow in a labyrinth seal for Taylor numbers of 0, 7,600, and 19,000 at an axial Reynolds number near 50,000. A hot-film anemometer with computer data acquisition was used in obtaining the measurements. The computations were made using a turbulent flow Navier-Stokes finite difference code. The QUICK differencing scheme was utilized in order to diminish false diffusion. Comparison between experiments and predictions are given for the axial and swirl velocity components and turbulent kinetic energy. Also, the substantial effect of the Taylor number on the pressure distribution is presented.
Spray Computations in a Centerbody Combustor
Authors: Raju M. S. , Sirignano W. A.
Published: October 2009

A hybrid Eulerian–Lagrangian method is employed to model the reactive flow field of a centerbody combustor. The unsteady two-dimensional gas-phase equations are represented in Eulerian coordinates and liquid-phase equations are formulated in Lagrangian coordinates. The gas-phase equations based on the conservation of mass, momentum, and energy are supplemented by turbulence and combustion models. The vaporization model takes into account the transient effects associated with the droplet heating and liquid-phase internal circulation. The integration scheme is based on the TEACH algorithm for gas-phase equations, the Runge-Kutta method for liquid-phase equations, and linear interpolation between the two coordinate systems. The calculations show that the droplet penetration and recirculation characteristics are strongly influenced by the gas- and liquid-phase interaction in such a way that most of the vaporization process is confined to the wake region of the centerbody, thereby improving the flame stabilization properties of the flow field.
Irreversibility and Thermoeconomics Based Design Optimization of a Ceramic Heat Exchanger
Authors: Ranasinghe J. , Aceves-Saborio S. , Reistad G. M.
Published: October 2009

This paper illustrates the optimization procedure for heat exchangers residing in complex power plants. A specific case of optimizing a new technology ceramic heat exchanger, which is a part of the complex power plant, is shown. The heat exchanger design methods presented are based on two different objective functions, namely, a modified irreversibility rate based objective function proposed by the authors in earlier work and an objective function based on thermoeconomics. This paper also extends existing work by illustrating a method to obtain the cost coefficients for thermoeconomic optimization, based on the use of an overall plant simulation model. A discussion on possible methods of improving the design guideposts obtained from irreversibility minimization analysis is also presented.
A New Method of Modeling Underexpanded Exhaust Plumes for Wind Tunnel Aerodynamic Testing
Authors: Salemann V. , Williams J. M.
Published: October 2009

A new method for modeling hot underexpanded exhaust plumes with cold model scale plumes in aerodynamic wind tunnel testing has been developed. The method is applicable to aeropropulsion testing where significant interaction between the exhaust and the free stream and aftbody may be present. The technique scales the model and nozzle external geometry, including the nozzle exit area, matches the model jet to free-stream dynamic pressure ratio to full-scale jet to free-stream dynamic pressure ratio, and matches the model thrust coefficient to full-scale thrust coefficient. The technique does not require scaling of the internal nozzle geometry. A generalized method of characteristic computer code was used to predict the plume shapes of a hot (γ = 1.2) half-scale nozzle of area ratio 3.2 and of a cold (γ = 1.4) model scale nozzle of area ratio 1.3, whose pressure ratio and area ratio were selected to satisfy the above criteria and other testing requirements. The plume shapes showed good agreement. Code validity was checked by comparing code results for cold air exhausting into a quiescent atmosphere to pilot surveys and shadowgraphs of model nozzle plumes taken in a static facility.
A Statistical Model of Bubble Coalescence and Its Application to Boiling Heat Flux Prediction—Part I: Model Development
Authors: Wu Wen , Jones Barclay G. , Newell Ty A.
Published: October 2009

In this work a statistical model is developed by deriving the probability density function (pdf) of bubble coalescence on boiling surface to describe the distribution of vapor bubble radius. Combining this bubble coalescence model with other existing models in the literature that describe the dynamics of bubble motion and the mechanisms of heat transfer, the surface heat flux in subcooled nucleate boiling can be calculated. By decomposing the surface heat flux into various components due to different heat transfer mechanisms, including forced convection, transient conduction, and evaporation, the effect of the bubble motion is identified and quantified. Predictions of the surface heat flux are validated with R134a data measured in boiling experiments and water data available in the literature, with an overall good agreement observed. Results indicate that there exists a limit of surface heat flux due to the increased bubble coalescence and the reduced vapor bubble lift-off radius as the wall temperature increased. Further investigation confirms the consistency between this limit value and the experimentally measured critical heat flux (CHF), suggesting that a unified mechanistic modeling to predict both the surface heat flux and CHF is possible. In view of the success of this statistical modeling, the authors tend to propose the utilization of probabilistic formulation and stochastic analysis in future modeling attempts on subcooled nucleate boiling.
Atomic clocks and coherent population trapping: Experiments for undergraduate laboratories
Authors: Belcher Nathan , Mikhailov Eugeniy E. , Novikova Irina
Published: October 2009

We demonstrate how to construct and operate a simple and affordable apparatus for producing coherent effects in atomic vapor and for investigating their applications in time-keeping and magnetometry. The apparatus consists of a vertical cavity surface emitting diode laser directly current-modulated using a tunable microwave oscillator to produce multiple optical fields needed for the observation of coherent population trapping. This effect allows very accurate measurement of the transition frequency between two ground state hyperfine sublevels, which can be used to construct a coherent population trapping-based atomic clock.
P. A. M. Dirac: Some strangeness in the proportion
Authors: Bernstein Jeremy
Published: October 2009

Dirac’s life and work is discussed, motivated in part by a recent biography on P. A. M. Dirac by Graham Farmelo.
Oscillations of a candle burning at both ends
Authors: Theodorakis Stavros , Paridi Kalliopi
Published: October 2009

A candle burning at both ends will oscillate vertically about the horizontal, forming the popular “candle see-saw” or “stearic motor.” The reason for these oscillations is that at any particular instant, more drops of liquid wax drip from the lower end than from the higher one. As a result, the lower side becomes lighter and moves upward, while the other side becomes heavier and moves downward, becoming the lower one. Thus the center of gravity oscillates continuously from one side to the other. We present a quantitative model describing these oscillations and verify it experimentally.
Resource Letter MP-2: Medical Physics
Authors: Hobbie Russell K. , Roth Bradley J.
Published: October 2009

This Resource Letter provides a guide to the literature on the uses of physics for the diagnosis and treatment of disease. It does not include molecular biophysics but does include biomedical engineering.
Molecular and Cellular Approaches to Memory Allocation in Neural Circuits
Authors: Silva Alcino J. , Zhou Yu , Rogerson Thomas , Shobe Justin , Balaji J.
Published: October 2009

Although memory allocation is a subject of active research in computer science, little is known about how the brain allocates information within neural circuits. There is an extensive literature on how specific types of memory engage different parts of the brain, and how neurons in these regions process and store information. Until recently, however, the mechanisms that determine how specific cells and synapses within a neural circuit (and not their neighbors) are recruited during learning have received little attention. Recent findings suggest that memory allocation is not random, but rather specific mechanisms regulate where information is stored within a neural circuit. New methods that allow tagging, imaging, activation, and inactivation of neurons in behaving animals promise to revolutionize studies of brain circuits, including memory allocation. Results from these studies are likely to have a considerable impact on computer science, as well as on the understanding of memory and its disorders.
The Optogenetic Catechism
Authors: Miesenböck Gero
Published: October 2009

An emerging set of methods enables an experimental dialogue with biological systems composed of many interacting cell types—in particular, with neural circuits in the brain. These methods are sometimes called “optogenetic” because they use light-responsive proteins (“opto-”) encoded in DNA (“-genetic”). Optogenetic devices can be introduced into tissues or whole organisms by genetic manipulation and be expressed in anatomically or functionally defined groups of cells. Two kinds of devices perform complementary functions: Light-driven actuators control electrochemical signals, while light-emitting sensors report them. Actuators pose questions by delivering targeted perturbations; sensors (and other measurements) signal answers. These catechisms are beginning to yield previously unattainable insight into the organization of neural circuits, the regulation of their collective dynamics, and the causal relationships between cellular activity patterns and behavior.
The Taste of Carbonation
Authors: Chandrashekar Jayaram , Yarmolinsky David , von Buchholtz Lars , Oka Yuki , Sly William , Ryba Nicholas J. P. , Zuker Charles S.
Published: October 2009

Gee Fizz

The next time you enjoy a carbonated beverage, you can do so with an enhanced understanding of the molecular mechanism that provides its distinctive flavor sensation.

Chandrashekar
et al.

(p.
443
) genetically ablated specific sets of taste cells in mice and found that the sensation of CO
2
was lost in animals lacking taste cells that sense sour flavors. A screen for genes specifically expressed in these cells revealed the gene encoding carbonic anhydrase 4, which catalyzes hydration of CO
2
to form bicarbonate and free protons. Knockout animals not expressing the carbonic anhydrase 4 gene also showed diminished sensation of CO
2
. The protons produced by the enzyme appear to be the actual molecules sensed by the sour-sensitive cells. This process, combined with tactile sensations, appears to be the source of the popular fizzy sensation.
Generation of Medaka Fish Haploid Embryonic Stem Cells
Authors: Yi Meisheng , Hong Ni , Hong Yunhan
Published: October 2009

Haploid Medaka Stem Cells

Although diploid embryonic stem cells have been generated by various means, there would also be value in deriving haploid stem cells. In these cells, recessive mutations in essential genes would show phenotypes that would not be apparent in heterozygous animals.

Yi
et al.

(p.
430
) used the medaka fish model system to generate haploid stem cells that show stable growth and pluripotency. In addition, a fertile female medaka fish was produced by haploid embryonic stem cell nuclear transfer into a normal egg. This system has potential for analyzing recessive genes, for example, in disease phenotypes or in various cell lineages in culture.
Phase Transitions, Melting Dynamics, and Solid-State Diffusion in a Nano Test Tube
Authors: Holmberg Vincent C. , Panthani Matthew G. , Korgel Brian A.
Published: October 2009

Confined Germanium Thermodynamics

When a material is confined to nanoscale volumes, the very high proportion of surface to bulk can alter its thermodynamic properties. This has been studied using in situ electron microscopy, but in most cases the volume of the material is not constrained.

Holmberg
et al.

(p.
405
) studied the thermodynamics of a germanium nanowire attached to a gold seed and coated with a carbon shell to restrict its volume, measuring the reaction temperature, as well as the liquid composition without changes in volume throughout the heating cycle. This enabled monitoring of phase behavior while the germanium was being heated, and tracking solid-state diffusion across the confined interface.
Deep-Sea Archaea Fix and Share Nitrogen in Methane-Consuming Microbial Consortia
Authors: Dekas Anne E. , Poretsky Rachel S. , Orphan Victoria J.
Published: October 2009

Balancing the Nitrogen Budget

Setting the global budget for elements presents difficult challenges, such as accounting for possibly unknown sources or sinks. An unresolved imbalance in the oceanic nitrogen budget suggests that there may be additional sources of biological nitrogen fixation in the deep sea. Using high-resolution imaging techniques,

Dekas
et al.

(p.
422
; see the Perspective by

Fulweiler

) observed direct assimilation of isotopically labeled N
2
by anaerobic methane-oxidizing archaea from deep marine sediment and the subsequent transfer of nitrogen to their sulfate-reducing bacterial symbionts. This slow and energetically costly conversion by archaea is dependent upon methane and requires physical contact with the associated bacterial partner. Such syntrophic consortia represent a potential source of nitrogen in the oceans and may help to balance the global nitrogen budget.
Toward a Malaria Vaccine
The Elusive Malaria Vaccine
Miracle or Mirage?

by Irwin W. Sherman

ASM Press, Washington, DC, 2009. 401 pp. $39.95. ISBN 9781555815158.
Authors: Greenwood Brian
Published: October 2009

Sherman offers an engaging, accessible history of efforts (so far unsuccessful) to develop an effective malaria vaccine.
How Good Are Neuron Models?
Authors: Gerstner Wulfram , Naud Richard
Published: October 2009

A recent competition encouraged modelers to predict neuronal activity. Which neuron model performed the best?
Laureates Analyzed Economics Outside Markets
Authors: Cho Adrian
Published: October 2009

This year's "Nobel Prize" in economics honors two researchers who studied economic behavior in nonfinancial settings: Elinor Ostrom of the University of Indiana, Bloomington, for her insights into the use of shared resources, and Oliver Williamson of the University of California, Berkeley, for his analysis of how a company decides what to do or make for itself and what to buy from others.
Enzyme Lets You Enjoy the Bubbly
Authors: Miller Greg
Published: October 2009

On page
443
of this week's issue of
Science
, a team of neuroscientists uses methods borrowed from electrophysiology and genetic engineering to identify a class of taste-receptor cells in the tongue that respond to carbon dioxide, the gas that gives sparkling beverages their fizz.
Tying Up the Solar System With a Ribbon of Charged Particles
Authors: Kerr Richard A.
Published: October 2009

Five papers published online in
Science
this week report that NASA's Interstellar Boundary Explorer revealed a sky-spanning "ribbon" of unexpectedly intense emissions of energetic neutral atoms.
Tonegawa Rethinks Japan's Premier Brain Research Center
Authors: Normile Dennis
Published: October 2009

This April, Nobelist Susumu Tonegawa became director of the RIKEN Brain Science Institute (BSI) near Tokyo, a part-time arrangement that allows him to maintain his lab at MIT. Tonegawa spoke with
Science
earlier this month about how he intends to raise BSI's game while coping with what he views as an inevitable downsizing.
Innate Immunity toAspergillusSpecies
Authors: Park Stacy J. , Mehrad Borna
Published: October 2009

All humans are continuously exposed to inhaledAspergillusconidia, yet healthy hosts clear the organism without developing disease and without the development of antibody- or cell-mediated acquired immunity to this organism. This suggests that for most healthy humans, innate immunity is sufficient to clear the organism. A failure of these defenses results in a uniquely diverse set of illnesses caused byAspergillusspecies, which includes diseases caused by the colonization of the respiratory tract, invasive infection, and hypersensitivity. A key concept in immune responses toAspergillusspecies is that the susceptibilities of the host determine the morphological form, antigenic structure, and physical location of the fungus. In this review, we summarize the current literature on the multiple layers of innate defenses againstAspergillusspecies that dictate the outcome of this host-microbe interaction.
Natural Killer Cell Dysfunction during Acute Infection with Foot-and-Mouth Disease Virus
Authors: Toka Felix N. , Nfon Charles , Dawson Harry , Golde William T.
Published: October 2009

Natural killer (NK) cells provide one of the initial barriers of cellular host defense against pathogens, in particular intracellular pathogens. The role of these cells in foot-and-mouth disease virus (FMDV) infection is unknown. Previously, we characterized the phenotype and function of NK cells from swine (F. N. Toka et al., J. Interferon Cytokine Res.29:179-192, 2009). In the present study, we report the analysis of NK cells isolated from animals infected with FMDV and tested ex vivo and show that NK-dependent cytotoxic activity against tumor cells as targets was impaired. More relevantly to this infection, the killing of target cells infected with FMDV also was inhibited. Further, the proportion of NK cells capable of producing gamma interferon and storing perforin was reduced. Peripheral blood mononuclear cells isolated from infected animals are not productively infected, but virus exposure in vivo resulted in the significant induction of NKp30 and Toll-like receptor 3 expression and the moderate activation of SOCS3 and interleukin-15 receptor mRNA. However, there was little alteration of mRNA expression from a number of other receptor genes in these cells, including SH2D1B and NKG2A (inhibitory) as well as NKp80, NKp46, and NKG2D (activating). These data indicate that this virus infection influences the ability of NK cells to recognize and eliminate FMDV-infected cells. In addition, a reduction in NK cell cytotoxicity coincided with the increase in virus titers, indicating the virus blocking of NK cell-associated innate responses, albeit temporarily. These effects likely culminate in brief but effective viral immune evasion, allowing the virus to replicate and disseminate within the host.
Dual-Function Antibodies to
Yersinia pestis
LcrV Required for Pulmonary Clearance of Plague
Authors: Eisele Nicholas A. , Anderson Deborah M.
Published: October 2009

Yersinia pestis
causes pneumonic plague, a necrotic pneumonia that rapidly progresses to death without early treatment. Antibodies to the protective antigen LcrV are thought to neutralize its essential function in the type III secretion system (TTSS) and by themselves are capable of inducing immunity to plague in mouse models. To develop multivalent LcrV antibodies as a therapeutic treatment option, we screened for monoclonal antibodies (MAbs) to LcrV that could prevent its function in the TTSS. Although we were able to identify single and combination MAbs that provided the high-level inhibition of the TTSS, these did not promote phagocytosis in vitro and were only weakly protective in a mouse pneumonic plague model. Only one MAb, BA5, was able to protect mice from pneumonic plague. In vitro, MAb BA5 blocked the TTSS with efficiency equal to or even less than that of other MAbs as single agents or as combinations, but its activity led to increased phagocytic uptake. Polyclonal anti-LcrV was superior to BA5 in promoting phagocytosis and also was more efficient in protecting mice from pneumonic plague. Taken together, the data support a hypothesis whereby the pulmonary clearance of
Y. pestis
by antibodies requires both the neutralization of the TTSS and the simultaneous stimulation of innate signaling pathways used by phagocytic cells to destroy pathogens.
Comparison of MRSA
Select
Agar, CHROMagar Methicillin-Resistant
Staphylococcus aureus
(MRSA) Medium, and Xpert MRSA PCR for Detection of MRSA in Nares: Diagnostic Accuracy for Surveillance Samples with Various Bacterial Densities
Authors: Wolk D. M. , Marx J. L. , Dominguez L. , Driscoll D. , Schifman R. B.
Published: October 2009

Rapid laboratory methods provide optimal support for active surveillance efforts to screen for methicillin-resistant
Staphylococcus aureus
(MRSA). Most laboratories struggle to determine the optimal use of resources, considering options to balance cost, speed, and diagnostic accuracy. To assess the performance of common methods, the first comparison of MRSA
Select
agar (MS) and CHROMagar MRSA (CA), with and without broth enrichment followed by a 24-h subculture to MS, was performed. Results were compared to those of the Xpert MRSA assay. For direct culture methods, the agreement between MS and CA was 98.8%. At 18 h, direct MS identified 93% of all positive samples from direct culture and 84% of those identified by the Xpert MRSA. For Trypticase soy broth-enriched MS culture, incubated overnight and then subcultured for an additional 24 h, the agreement with Xpert MRSA was 96%. The agreement between direct MS and Xpert MRSA was 100% when semiquantitative culture revealed a bacterial density of 2+ or greater; however, discrepancies between culture and Xpert MRSA arose for MRSA bacterial densities of 1+ or less, indicating low density as a common cause of false-negative culture results. Since 1+ or less was established as the most common MRSA carrier state, broth enrichment or PCR may be critical for the identification of all MRSA carriers who may be reservoirs for transmission. In this active-surveillance convenience sample, the use of broth enrichment followed by subculture to MS offered a low-cost but sensitive method for MRSA screening, with performance similar to that of Xpert MRSA PCR.
Development and Application of a Universal Hemoplasma Screening Assay Based on the SYBR Green PCR Principle
Authors: Willi Barbara , Meli Marina L. , Lüthy Ruedi , Honegger Hanspeter , Wengi Nicole , Hoelzle Ludwig E. , Reusch Claudia E. , Lutz Hans , Hofmann-Lehmann Regina
Published: October 2009

Hemotropic mycoplasmas (hemoplasmas) are the causative agents of infectious anemia in several mammalian species. Their zoonotic potential has recently been substantiated by the identification of a feline hemoplasma isolate in an immunocompromised human patient. Although species-specific diagnostic molecular methods have been developed, their application as screening tools is limited due to the species diversity of hemoplasmas. The goals of this study were to develop a universal hemoplasma screening assay with broad specificity based on the SYBR green PCR principle, to compare the assay with hemoplasma-specific TaqMan PCR, and to analyze potential tick vectors and human blood samples to address the zoonotic potential. The newly developed PCR assay based on the 16S rRNA gene amplified feline, canine, bovine, porcine, camelid, and murine hemoplasmas, as well asMycoplasma penetransandMycoplasma pneumoniae. The lower detection limit for feline and canine hemoplasmas was 1 to 10 copies/PCR. The assay exhibited 98.2% diagnostic sensitivity and 92.1% diagnostic specificity for feline hemoplasmas. All 1,950Ixodesticks were PCR negative, suggesting thatIxodesticks are not relevant vectors for the above-mentioned hemoplasma species in Switzerland. None of the 414 blood samples derived from anemic or immunocompromised human patients revealed a clear positive result. The SYBR green PCR assay described here is a suitable tool to screen for known and so-far-undiscovered hemoplasma species. Positive results should be confirmed by specific TaqMan PCR or sequencing.
Lymphocytic Choriomeningitis Virus-Induced Mortality in Mice Is Triggered by Edema and Brain Herniation
Authors: Matullo Christine M. , O'Regan Kevin J. , Hensley Harvey , Curtis Mark , Rall Glenn F.
Published: October 2009

Although much is known about lymphocytic choriomeningitis virus (LCMV) infection and the subsequent immune response in its natural murine host, some crucial aspects of LCMV-mediated pathogenesis remain undefined, including the underlying basis of the characteristic central nervous system disease that occurs following intracerebral (i.c.) challenge. We show that the classic seizures and paresis that occur following i.c. infection of adult, immunocompetent mice with LCMV are accompanied by anatomical and histological changes that are consistent with brain herniation, likely of the uncal subtype, as a causative basis for disease and precipitous death. Both by water weight determinations and by magnetic resonance imaging of infected brain tissues, edema was detected only at the terminal stages of disease, likely caused by the leakage of cerebrospinal fluid from the ventricles into the parenchyma. Furthermore, death was accompanied by unilateral pupillary dilation, which is indicative of uncal herniation. While immunohistochemical analysis revealed periventricular inflammation and a loss of integrity of the blood-brain barrier (BBB), these events preceded seizures by 2 to 3 days. Moreover, surviving perforin knockout mice showed barrier permeability equivalent to that of moribund, immunocompetent mice; thus, BBB damage does not appear to be the basis of LCMV-induced neuropathogenesis. Importantly, brain herniation can occur in humans as a consequence of injuries that would be predicted to increase intracranial pressure, including inflammation, head trauma, and brain tumors. Thus, a mechanistic dissection of the basis of LCMV neuropathogenesis may be informative for the development of interventive therapies to prevent this typically fatal human condition.
Anti-Glycoprotein H Antibody Impairs the Pathogenicity of Varicella-Zoster Virus in Skin Xenografts in the SCID Mouse Model
Authors: Vleck Susan E. , Oliver Stefan L. , Reichelt Mike , Rajamani Jaya , Zerboni Leigh , Jones Carol , Zehnder James , Grose Charles , Arvin Ann M.
Published: October 2009

Varicella-zoster virus (VZV) infection is usually mild in healthy individuals but can cause severe disease in immunocompromised patients. Prophylaxis with varicella-zoster immunoglobulin can reduce the severity of VZV if given shortly after exposure. Glycoprotein H (gH) is a highly conserved herpesvirus protein with functions in virus entry and cell-cell spread and is a target of neutralizing antibodies. The anti-gH monoclonal antibody (MAb) 206 neutralizes VZV in vitro. To determine the requirement for gH in VZV pathogenesis in vivo, MAb 206 was administered to SCID mice with human skin xenografts inoculated with VZV. Anti-gH antibody given at 6 h postinfection significantly reduced the frequency of skin xenograft infection by 42%. Virus titers, genome copies, and lesion size were decreased in xenografts that became infected. In contrast, administering anti-gH antibody at 4 days postinfection suppressed VZV replication but did not reduce the frequency of infection. The neutralizing anti-gH MAb 206 blocked virus entry, cell fusion, or both in skin in vivo. In vitro, MAb 206 bound to plasma membranes and to surface virus particles. Antibody was internalized into vacuoles within infected cells, associated with intracellular virus particles, and colocalized with markers for early endosomes and multivesicular bodies but not thetrans-Golgi network. MAb 206 blocked spread, altered intracellular trafficking of gH, and bound to surface VZV particles, which might facilitate their uptake and targeting for degradation. As a consequence, antibody interference with gH function would likely prevent or significantly reduce VZV replication in skin during primary or recurrent infection.
Human Regulatory T Cells Are Targets for Human Immunodeficiency Virus (HIV) Infection, and Their Susceptibility Differs Depending on the HIV Type 1 Strain
Authors: Moreno-Fernandez Maria E. , Zapata Wildeman , Blackard Jason T. , Franchini Genoveffa , Chougnet Claire A.
Published: October 2009

Regulatory T cells (Treg) are a subpopulation of CD4
+
T cells characterized by the suppressive activity they exert on effector immune responses, including human immunodeficiency virus (HIV)-specific immune responses. Because Treg express CXCR4 and CCR5, they represent potential targets for HIV; however, Treg susceptibility to HIV infection is still unclear. We therefore performed an extensive study of Treg susceptibility to HIV, using lab strains and primary isolates with either CCR5 or CXCR4 tropism. Furthermore, we quantified HIV infection at early and late time points of the virus life cycle. We found that Treg were clearly susceptible to HIV infection. Circulating Treg were not preferentially infected with HIV compared to effector T cells (Teff) in vivo. Conversely, in vitro infection with either CCR5-using (R5) or CXCR4-using (X4) viruses occurred with different dynamics. For instance, HIV infection by R5 viruses (lab strains and primary isolates) resulted in lower levels of infection in Treg compared with Teff at both early and late time points. In contrast, X4 viruses induced higher levels of infection in Treg compared to Teff at early time points, but this difference disappeared at the late time points of the virus life cycle. Our results suggest that the relative susceptibility of Treg to HIV infection compared to Teff varies, depending on both viral and host factors. These variations may play an important role in HIV pathogenesis.
Nanodisc-Incorporated Hemagglutinin Provides Protective Immunity against Influenza Virus Infection
Authors: Bhattacharya Palash , Grimme Steve , Ganesh Balaji , Gopisetty Anupama , Sheng Jian Rong , Martinez Osvaldo , Jayarama Shankar , Artinger Michael , Meriggioli Matthew , Prabhakar Bellur S.
Published: October 2009

Every year, influenza virus infection causes significant mortality and morbidity in human populations. Although egg-based inactivated viral vaccines are available, their effectiveness depends on the correct prediction of the circulating viral strains and is limited by the time constraint of the manufacturing process. Recombinant subunit vaccines are easier to manufacture with a relatively short lead time but are limited in their efficacy partly because the purified recombinant membrane proteins in the soluble form most likely do not retain their native membrane-bound structure. Nanodisc (ND) particles are soluble, stable, and reproducibly prepared discoid shaped nanoscale structures that contain a discrete lipid bilayer bound by two amphipathic scaffold proteins. Because ND particles permit the functional reconstitution of membrane/envelope proteins, we incorporated recombinant hemagglutinin (HA) from influenza virus strain A/New Caledonia/20/99 (H1N1) into NDs and investigated their potential to elicit an immune response to HA and confer immunity to influenza virus challenge relative to the commercial vaccines Fluzone and FluMist. HA-ND vaccination induced a robust anti-HA antibody response consisting of predominantly the immunoglobulin G1 (IgG1) subclass and a high hemagglutination inhibition titer. Intranasal immunization with HA-ND induced an anti-HA IgA response in nasal passages. HA-ND vaccination conferred protection that was comparable to that of Fluzone and FluMist against challenge with influenza virus strain A/Puerto Rico/8/1934 (H1N1).
The Bovine Immunodeficiency Virus Rev Protein: Identification of a Novel Lentiviral Bipartite Nuclear Localization Signal Harboring an Atypical Spacer Sequence
Authors: Gomez Corredor Andrea , Archambault Denis
Published: October 2009

The bovine immunodeficiency virus (BIV) Rev protein (186 amino acids [aa] in length) is involved in the nuclear exportation of partially spliced and unspliced viral RNAs. Previous studies have shown that BIV Rev localizes in the nucleus and nucleolus of infected cells. Here we report the characterization of the nuclear/nucleolar localization signals (NLS/NoLS) of this protein. Through transfection of a series of deletion mutants of BIV Rev fused to enhanced green fluorescent protein and fluorescence microscopy analyses, we were able to map the NLS region between aa 71 and 110 of the protein. Remarkably, by conducting alanine substitution of basic residues within the aa 71 to 110 sequence, we demonstrated that the BIV Rev NLS is bipartite, maps to aa 71 to 74 and 95 to 101, and is predominantly composed of arginine residues. This is the first report of a bipartite Rev (or Rev-like) NLS in a lentivirus/retrovirus. Moreover, this NLS is atypical, as the length of the sequence between the motifs composing the bipartite NLS, e.g., the spacer sequence, is 20 aa. Further mutagenesis experiments also identified the NoLS region of BIV Rev. It localizes mainly within the NLS spacer sequence. In addition, the BIV Rev NoLS sequence differs from the consensus sequence reported for other viral and cellular nucleolar proteins. In summary, we conclude that the nucleolar and nuclear localizations of BIV Rev are mediated via novel NLS and NoLS motifs.