bluuebunny/crossref_metadata_2025 huggingface dataset:
The Two-Flux Model Applied to Radiative Transfer and Forced Convection in the Laminar Boundary Layer on a Flat Plate
Authors: Malpica F. , Moreno N. , Tremante A.
Published: August 2003

This study presents the analysis of the thermal boundary layer considering combined convection and radiation in an absorbing, emitting, and scattering medium flowing over a flat plate. At high temperatures the presence of thermal radiation alters the temperature distribution in the boundary layer, which in turn affects the heat transfer at the wall. In many industrial applications, such as in the cooling of turbine and compressors blades, radiative heat transfer plays an important role. The treatment of heat transfer by combined convection and radiation in the boundary layer leads to a set of partial differential and integrodifferential equations, which must be solved simultaneously. The exact solutions are seldom possible and the investigators resort to approximate methods. In the present analysis the two-flux model is used to describe the radiative heat flux in the energy equation. This model reduces the equations that govern the problem to a set of coupled partial differential equations. A finite difference scheme, called “method of columns,” is used to transform the resulting equations into an ordinary differential equation system which simplifies the solution. Results for the temperature profile and heat fluxes showed close agreement with the thin and thick limits. The method proposed proves to be useful to investigate the effect of the different radiation parameters on the thermal boundary layer, and also to be accurate enough for engineering applications.
Wear Assessment in a Biodiesel Fueled Compression Ignition Engine
Authors: Agarwal A. K. , Bijwe J. , Das L. M.
Published: August 2003

Biodiesel is prepared using linseed oil and methanol by the process of transesterification. Use of linseed oil methyl ester (LOME) in a compression ignition engine was found to develop a highly compatible engine-fuel system with low emission characteristics. Two similar engines were operated using optimum biodiesel blend and mineral diesel oil, respectively. These were subjected to long-term endurance tests. Lubricating oil samples drawn from both engines after a fixed interval were subjected to elemental analysis. Quantification of various metal debris concentrations was done by atomic absorption spectroscopy (AAS). Wear metals were found to be about 30% lower for a biodiesel-operated engine system. Lubricating oil samples were also subjected to ferrography indicating lower wear debris concentrations for a biodiesel-operated engine. The additional lubricating property of LOME present in the fuel resulted in lower wear and improved life of moving components in a biodiesel-fuelled engine. However, this needed experimental verification and quantification. A series of experiments were thus conducted to compare the lubricity of various concentrations of LOME in biodiesel blends. Long duration tests were conducted using reciprocating motion in an SRV optimol wear tester to evaluate the coefficient of friction, specific wear rates, etc. The extent of damage, coefficient of friction, and specific wear rates decreased with increase in the percentage of LOME in the biodiesel blend. Scanning electron microscopy was conducted on the surfaces exposed to wear. The disk and pin using 20% biodiesel blend as the lubricating oil showed lesser damage compared to the one subjected to diesel oil as the lubricating fluid, confirming additional lubricity of biodiesel.
Degradation Effects on Combined Cycle Power Plant Performance—Part I: Gas Turbine Cycle Component Degradation Effects
Authors: Zwebek A. , Pilidis P.
Published: August 2003

This paper describes the effects of degradation of the main gas path components of the gas turbine topping cycle on the combined cycle gas turbine (CCGT) plant performance. First, the component degradation effects on the gas turbine performance as an independent unit are examined. It is then shown how this degradation is reflected on a steam turbine plant of the CCGT and on the complete combined cycle plant. TURBOMATCH, the gas turbine performance code of Cranfield University, was used to predict the effects of degraded gas path components of the gas turbine have on its performance as a whole plant. To simulate the steam (bottoming) cycle, another Fortran code was developed. Both codes were used together to form a complete software system that can predict the CCGT plant design point, off-design, and deteriorated (due to component degradation) performances. The results show that the overall output is very sensitive to many types of degradation, especially in the turbine of the gas turbine. Also shown is the effect on gas turbine exhaust conditions and how this affects the steam cycle.
Degradation Effects on Combined Cycle Power Plant Performance—Part II: Steam Turbine Cycle Component Degradation Effects
Authors: Zwebek A. , Pilidis P.
Published: August 2003

This is the second paper exploring the effects of the degradation of different components on combined cycle gas turbine (CCGT) plant performance. This paper investigates the effects of degraded steam path components of steam turbine (bottoming) cycle have on CCGT power plant performance. Areas looked at were, steam turbine fouling, steam turbine erosion, heat recovery steam generator degradation (scaling and/or ashes deposition), and condenser degradation. The effect of gas turbine back-pressure on plant performance due to HRSG degradation is also discussed. A general simulation FORTRAN code was developed for the purpose of this study. This program can calculate the CCGT plant design point performance, off-design plant performance, and plant deterioration performance. The results obtained are presented in a graphical form and discussed.
Endothermic Phenomena in Diesel Particulate Filters During Regeneration
Authors: Kyriakis N. , Manikas T. , Pistikopoulos P. , Vouitsis E.
Published: August 2003

Endothermic phenomena were identified during the regeneration of the porous ceramic diesel particulate trap. These phenomena were experimentally investigated and they were found to be related to the cerium content of the fuel used for the trap loading and regeneration and to the soot mass accumulated in the trap. Carbon mass and energy balance through the regeneration process reveals that these phenomena cannot be attributed to chemical reactions in the trap. It is assumed that they are due to the effect of regeneration on the radial flow distribution through the trap, an assumption remaining to be experimentally tested.
Numerical Study of Nonreacting Gas Turbine Combustor Swirl Flow Using Reynolds Stress Model
Authors: Yang S. L. , Siow Y. K. , Peschke B. D. , Tacina R. R.
Published: August 2003

This paper presents recent research on the use of a Reynolds stress turbulence model (RSTM) for three-dimensional flowfield simulation inside gas turbine combustors. It intends to show the motivations for using the RSTM in engine flow simulation, to present a further validation of the RSTM implementation in the KIVA code using the available experimental data, and to provide comparisons between RSTM and k-ε turbulence model results for chemically nonreacting swirling flows. The results show that, for high-degree swirl flow, the RSTM can provide predictions in favorable agreement with the experimental data, and that the RSTM predicts recirculations and high velocity gradients better than does the k-ε turbulence model. The results also indicate that the choice of swirler has a significant influence on the structure of the combustor flowfield.
Air Fuel Ratio Estimation Using In-Cylinder Pressure Frequency Analysis
Authors: Cavina N. , Ponti F.
Published: August 2003

This paper presents an original approach to estimate the air-fuel ratio (AFR) of the mixture that burned inside a given cylinder of a spark-ignited (SI) internal combustion engine, using the information hidden in the corresponding in-cylinder pressure signal. In modern closed-loop fuel injection control strategies, the feedback signal is usually given by one (or more) heated exhaust gas oxygen (HEGO) sensor(s), mounted in the exhaust manifold(s). The information that such sensors give is related to the stoichiometry of the mixture that burned inside the cylinders. The HEGO sensor is not able to evaluate the AFR value precisely, being only able to determine whether the mixture was rich or lean. This information is sufficient to allow the implementation of a closed-loop strategy for injection time control. Generally speaking, such strategy could be improved in terms of readiness and precision by directly measuring (or by estimating) the actual AFR. Universal exhaust gas oxygen (UEGO) sensors are still considered expensive and their use is mostly limited to laboratory and racing applications, even if some automotive manufacturers have started installing such sensors on board passenger cars, as part of an effort to comply with ULEV (ultra low emission vehicles) regulations. For this reason the idea of estimating AFR values from other signals has received great attention in the past few years. A new approach based on in-cylinder pressure frequency analysis is presented here.
Statistical Correlation Between the Crankshaft’s Speed Variation and Engine Performance—Part I: Theoretical Model
Authors: Taraza D.
Published: August 2003

The goal of this two-part paper is to develop a methodology using the variation of the measured crankshaft speed to calculate the mean indicated pressure (MIP) of a multicylinder engine and to detect cylinders that are lower contributors to the total engine output. Both the gas pressure torque and the crankshaft’s speed are, under steady-state operating conditions, periodic functions of the crank angle and may be expressed by Fourier series. For the lower harmonic orders, the dynamic response of the crankshaft approaches the response of a rigid body and that makes it is possible to establish correlations between the amplitudes and phases of the corresponding harmonic orders of the crankshaft’s speed and of the gas pressure torque. The inherent cycle-to-cycle variation in the operation of the cylinders requires a statistical approach to the problem. The first part of the paper introduces the statistical model for a harmonic component of the gas pressure torque and determines the correlation between the amplitudes and phases of the harmonic components of the gas pressure torque and the MIP of the engine. In the second part of the paper the statistical model is used to calculate the MIP and to detect deficient cylinders in the operation of a six-cylinder four-stroke diesel engine.
Subsonic Elector Nozzle Limiting Flow Conditions
Authors: De Chant L. J.
Published: August 2003

This paper describes an analytical method used to provide information concerning limiting flows for subsonic ejector nozzles. Three potential limiting flows have been identified and modeled using reduced control volume based analysis: (1) incipient reverse flow into the secondary inlet, (2) choked flow in the secondary inlet, and (3) choked flow in the exit mixing stream. Comparison of the methods developed here with the classical control volume portion of an ejector nozzle code have been performed and show good agreement. As such, it is concluded, that within the scope of one-dimensional control-volume based computations, that the methods developed here provide an efficient tool to help delimit the design space acceptable for ejector operation.
Reducing Lateral Vibration of a Rotor Passing Through Critical Speeds by Phase Modulating
Authors: Wang S.-M. , Lu Q.-S. , Twizell E. H.
Published: August 2003

A method is presented to reduce the lateral vibration amplitude of an unbalanced rotor accelerating or decelerating through its critical speed, by means of modulating the response phase with varying acceleration rate. Theoretical and numerical analysis on the amplitude and the phase characteristics of lateral vibration of a rotor model are made. Numerical results show that when the rotor passes through its critical speed with a modulated phase, the response amplitude can be reduced by 20% or so, compared with the nonmodulated (constant) acceleration case.
Interpretation of Weighted-Least-Squares Gas Path Analysis Results
Authors: Doel D. L.
Published: August 2003

Gas turbine performance analysis programs convert raw measurements (thrust, fuel flow, gas path temperatures, and pressures) into engine and component figures of merit (e.g., specific fuel consumption, component efficiencies). The derived parameters allow a diagnostician to recognize a poorly performing engine and help to identify the root cause for the problem. These goals can be foiled by measurement problems or by analysis assumptions embedded in the programs. A gifted analyst learns to recognize measurement or assumption problems via characteristic “fingerprints” in the program output. The latest data analysis tools tackle the same issues using a weighted-least-squares algorithm which estimates sensor errors at the same time component health is being determined. The weighted-least-squares algorithm modifies the “fingerprint” of a measurement problem and also that of a problem-free solution. To develop intuition for these new programs, the analyst must understand how weighted-least-squares works and how normal and problem situations are reflected in the output. This paper describes the weighted-least-squares algorithm, as implemented in GE’s TEMPER program, with the goal of stimulating a new intuition for interpreting gas path analysis results.
Nonlinear Engine Component Fault Diagnosis From a Limited Number of Measurements Using a Combinatorial Approach
Authors: Aretakis N. , Mathioudakis K. , Stamatis A.
Published: August 2003

A method for diagnosing component faults of jet engines is presented. It uses nonlinear gas path analysis techniques to determine the values of health parameters, with the help of a suitably formulated engine simulation model. The incentive of the method is to achieve the determination of the values of component health indices when a limited number of measured quantities is available, which do not allow the determination of all the fault indices simultaneously. A combinatorial approach is introduced, in order to circumvent the problem of the insufficient information for determining a full set of indices. After obtaining a set of possible solutions, a selection procedure is applied to isolate the ones that can give the actual fault identity. Quantification of the fault comes at a final step, when the faulty component has been identified. Different scenarios of faults on a twin spool partially mixed turbofan engine are considered in order to demonstrate the effectiveness of the method. The limitations of the method are also discussed.
Time Domain Simulation of Combustion Instabilities in Annular Combustors
Authors: Pankiewitz C. , Sattelmayer T.
Published: August 2003

A novel method for the simulation of combustion instabilities in annular combustors is presented. It is based on the idea to solve the equations governing the acoustics in the time domain and couple them to a model for the heat release in the flames. The linear wave equation describing the temporal and spatial evolution of the pressure fluctuations is implemented in a finite element code. Providing high flexibility, this code in principle allows both the computational domain to be of arbitrary shape and the mean flow to be included. This yields applicability to realistic technical combustors. The fluctuating heat release acting as a volume source appears as a source term in the equation to be solved. Employing a time-lag model, the heat release rate at each individual burner is related to the velocity in the corresponding burner at an earlier time. As saturation also is considered, a nonlinearity is introduced into the system. Starting the simulation from a random initial perturbation with suitable values for the parameters of the heat release model, a self-excited instability is induced, leading to a finite-amplitude limit cycle oscillation. The feasibility of the approach is demonstrated with three-dimensional simulations of a simple model annular combustor. The effect of the model parameters and of axial mean flow on the stability and the shape of the excited modes is shown.
Flashback Limits for Combustion Induced Vortex Breakdown in a Swirl Burner
Authors: Kro¨ner M. , Fritz J. , Sattelmayer T.
Published: August 2003

Flame flashback from the combustion chamber into the mixing zone limits the reliability of swirl stabilized lean premixed combustion in gas turbines. In a former study, the combustion induced vortex breakdown (CIVB) has been identified as a prevailing flashback mechanism of swirl burners. The present study has been performed to determine the flashback limits of a swirl burner with cylindrical premixing tube without centerbody at atmospheric conditions. The flashback limits, herein defined as the upstream flame propagation through the entire mixing tube, have been detected by a special optical flame sensor with a high temporal resolution. In order to study the effect of the relevant parameters on the flashback limits, the burning velocity of the fuel has been varied using four different natural gas-hydrogen-mixtures with a volume fraction of up to 60% hydrogen. A simple approach for the calculation of the laminar flame speeds of these mixtures is proposed which is used in the next step to correlate the experimental results. In the study, the preheat temperature of the fuel mixture was varied from 100°C to 450°C in order to investigate influence of the burning velocity as well as the density ratio over the flame front. Moreover, the mass flow rate has been modified in a wide range as an additional parameter of technical importance. It was found that the quenching of the chemical reaction is the governing factor for the flashback limit. A Peclet number model was successfully applied to correlate the flashback limits as a function of the mixing tube diameter, the flow rate and the laminar burning velocity. Using this model, a quench factor can be determined for the burner, which is a criterion for the flashback resistance of the swirler and which allows to calculate the flashback limit for all operating conditions on the basis of a limited number of flashback tests.
A Gas Turbine-Based Hybrid Vehicle—Part II: Technological and Configuration Issues
Authors: Capata R. , Cioffarelli E. , Sciubba E.
Published: August 2003

A hybrid propulsion system for a passenger car is described and its preliminary design and performance discussed. A gas turbine operating in a controlled on-off mode, a generator, a battery pack, an inverter, and an electric motor constitute the power system, with an electronic vehicle management unit supervising the system for control and regulation. Road simulation tests are presented, based on standard ECC driving mission cycles. The turbogas performance might be improved adopting ceramic blades, with a possible increase of the TIT (turbine inlet temperature), and a consequent increase of its efficiency. The paper reports on the first results of a study in progress, within a joint research program between the University of Roma 1 “La Sapienza” and the Italian Research Centre of ENEA-Casaccia.
Gas Turbine Engine Durability Impacts of High Fuel-Air Ratio Combustors—Part I: Potential for Secondary Combustion of Partially Reacted Fuel
Authors: Lukachko S. P. , Kirk D. R. , Waitz I. A.
Published: August 2003

Demand for greater engine efficiency and thrust-to-weight ratio has driven the production of aircraft engines with higher core temperatures and pressures. Such engines operate at higher fuel-air ratios, resulting in the potential for significant heat release through the turbine if species, such as CO and HC, are emitted from the combustor in large quantities. This paper outlines the magnitude and potential for turbine heat release in current and future engines. The analysis suggests that high fuel-air ratio designs may have to consider changes to cooling strategies to accommodate secondary combustion. A characteristic time methodology is developed to evaluate the chemical and fluid mechanical conditions that lead to combustion within the turbine. Local species concentrations partly determine the potential for energy release. An energy release parameter, here defined as a maximum increase in total temperature ΔTt, is used to specify an upper limit on the magnitude of impact. The likelihood of such impacts is set by the convective, mixing, and chemical processes that determine the fate and transport of species through the turbine. Appropriately defined Damko¨hler numbers (Da)—the comparative ratio of a characteristic flow time τflow to a characteristic chemical time τchem—are employed to capture the macroscopic physical features controlling the flow-chemistry interactions that lead to heat release in the turbine.
Impact of Ethane and Propane Variation in Natural Gas on the Performance of a Model Gas Turbine Combustor
Authors: Flores R. M. , McDonell V. G. , Samuelsen G. S.
Published: August 2003

In the area of stationary power generation, there exists a growing interest in understanding the role that gaseous fuel composition plays on the performance of natural gas-fired gas turbine systems. In this study, an atmospherically fired model gas turbine combustor with a fuel flexible fuel/air premixer is employed to investigate the impact of significant amounts of ethane and propane addition into a baseline natural gas fuel supply. The impacts of these various fuel compositions, in terms of the emissions of NOx and CO, and the coupled impact of the degree of fuel/air mixing, are captured explicitly for the present system by means of a statistically oriented testing methodology. These explicit expressions are also compared to emissions maps that encompass and expand beyond the statistically based test matrix to verify the validity of the employed statistical approach.
Gas Turbine Engine Durability Impacts of High Fuel-Air Ratio Combustors—Part II: Near-Wall Reaction Effects on Film-Cooled Heat Transfer
Authors: Kirk D. R. , Guenette G. R. , Lukachko S. P. , Waitz I. A.
Published: August 2003

As commercial and military aircraft engines approach higher total temperatures and increasing overall fuel-to-air ratios, the potential for significant chemical reactions on a film-cooled surface is enhanced. Currently, there is little basis for understanding the effects on aero-performance and durability due to such secondary reactions. A shock tube experiment was employed to generate short duration, high temperature (1000–2800 K) and pressure (6 atm) flows over a film-cooled flat plate. The test plate contained two sets of 35 deg film cooling holes that could be supplied with different gases, one side using air and the other nitrogen. A mixture of ethylene and argon provided a fuel rich freestream that reacted with the air film resulting in near wall reactions. The relative increase in surface heat flux due to near wall reactions was investigated over a range of fuel levels, momentum blowing ratios (0.5–2.0), and Damko¨hler numbers (ratio of flow to chemical time scales) from near zero to 30. For high Damko¨hler numbers, reactions had sufficient time to occur and increased the surface heat flux by 30 percent over the inert cooling side. When these results are appropriately scaled, it is shown that in some situations of interest for gas turbine engine environments significant increases in surface heat flux can be produced due to chemical reactions in the film-cooling layer. It is also shown that the non-dimensional parameters Damko¨hler number (Da), blowing ratio (B), heat release potential (H*), and scaled heat flux Qs are the appropriate quantities to predict the augmentation in surface heat flux that arises due to secondary reactions.
FACT Facilitates Transcription-Dependent Nucleosome Alteration
Authors: Belotserkovskaya Rimma , Oh Sangtaek , Bondarenko Vladimir A. , Orphanides George , Studitsky Vasily M. , Reinberg Danny
Published: August 2003

The FACT (facilitates chromatin transcription) complex is required for transcript elongation through nucleosomes by RNA polymerase II (Pol II) in vitro. Here, we show that FACT facilitates Pol II–driven transcription by destabilizing nucleosomal structure so that one histone H2A-H2B dimer is removed during enzyme passage. We also demonstrate that FACT possesses intrinsic histone chaperone activity and can deposit core histones onto DNA. Importantly, FACT activity requires both of its constituent subunits and is dependent on the highly acidic C terminus of its larger subunit, Spt16. These findings define the mechanism by which Pol II can transcribe through chromatin without disrupting its epigenetic status.
Tracking FACT and the RNA Polymerase II Elongation Complex Through Chromatin in Vivo
Authors: Saunders Abbie , Werner Janis , Andrulis Erik D. , Nakayama Takahiro , Hirose Susumu , Reinberg Danny , Lis John T.
Published: August 2003

RNA polymerase II (Pol II) transcription through nucleosomes is facilitated in vitro by the protein complex FACT (
Fa
cilitates
C
hromatin
T
ranscription). Here we show that FACT is associated with actively transcribed Pol II genes on
Drosophila
polytene chromosomes. FACT displays kinetics of recruitment and of chromosome tracking in vivo similar to Pol II and elongation factors Spt5 and Spt6. Interestingly, FACT does not colocalize with Pol III–transcribed genes, which are known to undergo nucleosome transfer rather than disassembly in vitro. Our observations are consistent with FACT being restricted to transcription that involves nucleosome disassembly mechanisms.
Antiretroviral Drugs for Tuberculosis Control in the Era of HIV/AIDS
Authors: Williams Brian G. , Dye Christopher
Published: August 2003

Human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) has dramatically increased the incidence of tuberculosis (TB) in subSaharan Africa, where up to 60% of TB patients are coinfected with HIV and each year 200,000 TB deaths are attributable to HIV coinfection. Now HIV threatens control of TB in Asia, Eastern Europe, and Latin America. Antiretroviral (ARV) drugs can prevent TB by preserving immunity, but cohort analysis shows that early therapy, plus high levels of coverage and compliance, will be needed to avert a significant fraction of TB cases. However, ARV drugs could enhance the treatment of TB, and TB programs provide an important entry point for the treatment of HIV/AIDS.
Stability of Retrieved Memory: Inverse Correlation with Trace Dominance
Authors: Eisenberg Mark , Kobilo Tali , Berman Diego E. , Dudai Yadin
Published: August 2003

In memory consolidation, the memory trace stabilizes and becomes resistant to certain amnesic agents. The textbook account is that for any memorized item, consolidation starts and ends just once. However, evidence has accumulated that upon activation in retrieval, the trace may reconsolidate. Whereas some authors reported transient renewed susceptibility of retrieved memories to consolidation blockers, others could not detect it. Here, we report that in both conditioned taste aversion in the rat and fear conditioning in the medaka fish, the stability of retrieved memory is inversely correlated with the control of behavior by that memory. This result may explain some conflicting findings on reconsolidation of activated memories.
Predominant Autoantibody Production by Early Human B Cell Precursors
Authors: Wardemann Hedda , Yurasov Sergey , Schaefer Anne , Young James W. , Meffre Eric , Nussenzweig Michel C.
Published: August 2003

During B lymphocyte development, antibodies are assembled by random gene segment reassortment to produce a vast number of specificities. A potential disadvantage of this process is that some of the antibodies produced are self-reactive. We determined the prevalence of self-reactive antibody formation and its regulation in human B cells. A majority (55 to 75%) of all antibodies expressed by early immature B cells displayed self-reactivity, including polyreactive and anti-nuclear specificities. Most of these autoantibodies were removed from the population at two discrete checkpoints during B cell development. Inefficient checkpoint regulation would lead to substantial increases in circulating autoantibodies.
Phonon Dispersions of fcc δ-Plutonium-Gallium by Inelastic X-ray Scattering
Authors: Wong Joe , Krisch Michael , Farber Daniel L. , Occelli Florent , Schwartz Adam J. , Chiang Tai-C. , Wall Mark , Boro Carl , Xu Ruqing
Published: August 2003

We report an experimental determination of the phonon dispersion curves in a face-centered cubic (fcc) δ-plutonium–0.6 weight % gallium alloy. Several unusual features, including a large elastic anisotropy, a small-shear elastic modulus C′, a Kohn-like anomaly in the T
1
[011] branch, and a pronounced softening of the [111] transverse modes, are found. These features can be related to the phase transitions of plutonium and to strong coupling between the lattice structure and the 5f valence instabilities. Our results also provide a critical test for theoretical treatments of highly correlated 5f electron systems as exemplified by recent dynamical mean field theory calculations for δ-plutonium.
Tidally Controlled Stick-Slip Discharge of a West Antarctic Ice
Authors: Bindschadler Robert A. , King Matt A. , Alley Richard B. , Anandakrishnan Sridhar , Padman Laurence
Published: August 2003

A major West Antarctic ice stream discharges by sudden and brief periods of very rapid motion paced by oceanic tidal oscillations of about 1 meter. Acceleration to speeds greater than 1 meter per hour and deceleration back to a stationary state occur in minutes or less. Slip propagates at approximately 88 meters per second, suggestive of a shear wave traveling within the subglacial till. A model of an episodically slipping friction-locked fault reproduces the observed quasi-periodic event timing, demonstrating an ice stream's ability to change speed rapidly and its extreme sensitivity to subglacial conditions and variations in sea level.
Transcription Elongation Factors Repress Transcription Initiation from Cryptic Sites
Authors: Kaplan Craig D. , Laprade Lisa , Winston Fred
Published: August 2003

Previous studies have suggested that transcription elongation results in changes in chromatin structure. Here we present studies of
Saccharomyces cerevisiae
Spt6, a conserved protein implicated in both transcription elongation and chromatin structure. Our results show that, surprisingly, an
spt6
mutant permits aberrant transcription initiation from within coding regions. Furthermore, transcribed chromatin in the
spt6
mutant is hypersensitive to micrococcal nuclease, and this hypersensitivity is suppressed by mutational inactivation of RNA polymerase II. These results suggest that Spt6 plays a critical role in maintaining normal chromatin structure during transcription elongation, thereby repressing transcription initiation from cryptic promoters. Other elongation and chromatin factors, including Spt16 and histone H3, appear to contribute to this control.
On Over-Weighting the Bottom Line
Authors: Baltimore David
Published: August 2003

Universities in the Marketplace
The Commercialization of Higher Education. Derek Bok. Princeton University Press, Princeton, NJ, 2003. 247 pp. $22.95, £15.95. ISBN 0-691-11412-9.

Bok discusses what he sees as the inherent dangers that arise when universities undertake money-making ventures with corporations.
Encoding Predictive Reward Value in Human Amygdala and Orbitofrontal Cortex
Authors: Gottfried Jay A. , O'Doherty John , Dolan Raymond J.
Published: August 2003

Adaptive behavior is optimized in organisms that maintain flexible representations of the value of sensory-predictive cues. To identify central representations of predictive reward value in humans, we used reinforcer devaluation while measuring neural activity with functional magnetic resonance imaging. We presented two arbitrary visual stimuli, both before and after olfactory devaluation, in a paradigm of appetitive conditioning. In amygdala and orbitofrontal cortex, responses evoked by a predictive target stimulus were decreased after devaluation, whereas responses to the nondevalued stimulus were maintained. Thus, differential activity in amygdala and orbitofrontal cortex encodes the current value of reward representations accessible to predictive cues.
A Polemic on Probability
Authors: Jaffe Andrew H.
Published: August 2003

Probability Theory
The Logic of Science. by E. T. Jaynes. G. Larry Bretthorst, Ed. Cambridge University Press, New York, 2003. 757 pp., $60, £45. ISBN 0-521-59271-2.

In a work intended as both a textbook and reference for researchers who must make inferences from incomplete data, Jaynes argues that the standard rules of probability are best interpreted as principles in logic.
Preparing Protein Microarrays by Soft-Landing of Mass-Selected Ions
Authors: Ouyang Zheng , Takáts Zoltán , Blake Thomas A. , Gologan Bogdan , Guymon Andy J. , Wiseman Justin M. , Oliver Justin C. , Davisson V. Jo , Cooks R. Graham
Published: August 2003

Intact, multiply protonated proteins of particular mass and charge were selected from ionized protein mixtures and gently landed at different positions on a surface to form a microarray. An array of cytochrome c, lysozyme, insulin, and apomyoglobin was generated, and the deposited proteins showed electrospray ionization mass spectra that matched those of the authentic compounds. Deposited lysozyme and trypsin retained their biological activity. Multiply charged ions of protein kinase A catalytic subunit and hexokinase were also soft-landed into glycerol-based liquid surfaces. These soft-landed kinases phosphorylated LRRASLG oligopeptide and D-fructose, respectively.
Sexual Cycle of
Cryptococcus neoformans
var.
grubii
and Virulence of Congenic
a
and α Isolates
Authors: Nielsen Kirsten , Cox Gary M. , Wang Ping , Toffaletti Dena L. , Perfect John R. , Heitman Joseph
Published: August 2003

Cryptococcus neoformans
is a human-pathogenic fungus that has evolved into three distinct varieties that infect most prominently the central nervous system. A sexual cycle involving haploid cells of a and α mating types has been reported for two varieties (
C. neoformans
var.
neoformans
, serotype D, and
C. neoformans
var.
gattii
, serotypes B and C), yet the vast majority of infections involve a distinct variety (
C. neoformans
var.
grubii
, serotype A) that has been thought to be clonal and restricted to the α mating type. We recently identified the first serotype A isolate of the a mating type which had been thought to be extinct (strain 125.91). Here we report that this unusual strain can mate with a subset of pathogenic serotype A strains to produce a filamentous dikaryon with fused clamp connections, basidia, and viable recombinant basidiospores. One meiotic segregant mated poorly with the serotype A reference strain H99 but robustly with a
crg1
mutant that lacks a regulator of G protein signaling and is hyperresponsive to mating pheromone. This meiotic segregant was used to create congenic a and α mating type serotype A strains. Virulence tests with rabbit and murine models of cryptococcal meningitis showed that the serotype A congenic a and α mating type strains had equivalent virulence in animal models, in contrast to previous studies linking the α mating type to increased virulence in congenic serotype D strains. Our studies highlight a role for sexual recombination in the evolution of a human fungal pathogen and provide a robust genetic platform to establish the molecular determinants of virulence.
Pathology ofPlasmodium chabaudi chabaudiInfection and Mortality in Interleukin-10-Deficient Mice Are Ameliorated by Anti-Tumor Necrosis Factor Alpha and Exacerbated by Anti-Transforming Growth Factor β Antibodies
Authors: Li Ching , Sanni Latifu A. , Omer Fakhreldin , Riley Eleanor , Langhorne Jean
Published: August 2003

Interleukin-10 (IL-10)-deficient (IL-10−/−) mice infected withPlasmodium chabaudi(AS) suffer a more severe disease and exhibit a higher rate of mortality than control C57BL/6 mice. Here, we show that a drop in body temperature to below 28°C and pronounced hypoglycemia of below 3 mM are reliable indicators of a lethal infection. Elevated inflammatory responses have been shown to accompany pathology in infected IL-10−/−mice. We show that neutralization of tumor necrosis factor alpha (TNF-α) in IL-10−/−mice abolishes mortality and ameliorates the hypothermia, weight loss, and anemia but does not affect the degree of hypoglycemia. These data suggest that TNF-α is involved in some of the pathology associated with aP. chabaudiinfection in IL-10−/−mice but other factors play a role. IL-10−/−mice that survive a primary infection have been shown to control gamma interferon (IFN-γ) and TNF-α production, indicating that other cytokines or mechanisms may be involved in their down-regulation. Significantly higher levels of transforming growth factor β (TGF-β), a cytokine with such properties, are present in the plasma of infected IL-10−/−mice at a time that coincides with the disappearance of IFN-γ and TNF-α from the blood. Neutralization of TGF-β in IL-10−/−mice resulted in higher circulating amounts of TNF-α and IFN-γ, and all treated IL-10−/−mice died within 12 days with increased pathology but with no obvious increase in parasitemia. Our data suggest that a tight regulation of the balance between regulatory cytokines such as IL-10 and TGF-β and inflammatory cytokines such as IFN-γ and TNF-α is critical for survival in a mouse malaria infection.
A DNA Vaccine Encoding Cu,Zn Superoxide Dismutase ofBrucella abortusInduces Protective Immunity in BALB/c Mice
Authors: Oñate Angel A. , Céspedes Sandra , Cabrera Alex , Rivers Rodolfo , González Andrés , Muñoz Carola , Folch Hugo , Andrews Edilia
Published: August 2003

This study was conducted to evaluate the immunogenicity and protective efficacy of a DNA vaccine encodingBrucella abortusCu,Zn superoxide dismutase (SOD). Intramuscular injection of plasmid DNA carrying the SOD gene (pcDNA-SOD) into BALB/c mice elicited both humoral and cellular immune responses. Animals injected with pcDNA-SOD developed SOD-specific antibodies which exhibited a dominance of immunoglobulin G2a (IgG2a) over IgG1. In addition, the DNA vaccine elicited a T-cell-proliferative response and also induced the production of gamma interferon, but not interleukin-10 (IL-10) or IL-4, upon restimulation with either recombinant SOD or crudeBrucellaprotein, suggesting the induction of a typical T-helper-1-dominated immune response in mice. The pcDNA-SOD (but not the control vector) induced a strong, significant level of protection in BALB/c mice against challenge withB. abortusvirulent strain 2308; the level of protection was similar to the one induced byB. abortusvaccine strain RB51. Altogether, these data suggest that pcDNA-SOD is a good candidate for use in future studies of vaccination against brucellosis.
Cryptococcus neoformansVirulence Is Enhanced after Growth in the Genetically Malleable HostDictyostelium discoideum
Authors: Steenbergen Judith N. , Nosanchuk Joshua D. , Malliaris Stephanie D. , Casadevall Arturo
Published: August 2003

Cryptococcus neoformansis an encapsulated, environmental fungus that can cause life-threatening meningitis. Pathogenicity ofC. neoformansfor macrophages and vertebrate hosts may be a mechanism selected in evolution for protection against environmental predators. In this study, we investigated whetherDictyostelium discoideumcould serve as an alternate host forC. neoformans. D. discoideumhas a defined genetic system which provides significant advantages for the study of fungus-amoeba interactions. Our results show thatD. discoideumis susceptible to infection withC. neoformansand that the interactions are similar to those described previously for this fungus with macrophages andAcanthamoeba castellanii. AcapsularC. neoformanscells did not replicate when coincubated withD. discoideum. However, incubation of acapsularC. neoformanswithD. discoideummutants defective in myosin VII synthesis resulted in infection, validating the concept that avirulent organisms can be virulent in impaired hosts even at the unicellular level. Phagocytosis ofC. neoformansbyD. discoideumcould be inhibited with capsule-specific antibodies and various sugars. Passage of an encapsulatedC. neoformansstrain throughD. discoideumcultures increased virulence and was accompanied by larger capsules and faster time to melanization. These results add to the evidence implicating soil ameboid predators as important factors for the maintenance ofC. neoformansvirulence in the environment and suggest thatD. discoideumpromises to be an extremely useful system for studying the interaction ofC. neoformanswith phagocytic cells.
Contribution of the Twin Arginine Translocation System to the Virulence of Enterohemorrhagic
Escherichia coli
O157:H7
Authors: Pradel Nathalie , Ye Changyun , Livrelli Valérie , Xu Jianguo , Joly Bernard , Wu Long-Fei
Published: August 2003

Shiga toxin-producing
Escherichia coli
O157:H7 is a major food-borne infectious pathogen. In order to analyze the contribution of the twin arginine translocation (TAT) system to the virulence of
E. coli
O157:H7, we deleted the
tatABC
genes of the O157:H7 EDL933 reference strain. The mutant displayed attenuated toxicity on Vero cells and completely lost motility on soft agar plates. Further analyses revealed that the Δ
tatABC
mutation impaired the secretion of the Shiga toxin 1 (Stx1) and abolished the synthesis of H7 flagellin, which are two major known virulence factors of enterohemorrhagic
E. coli
O157:H7. Expression of the EDL933
stxAB
1
genes in
E. coli
K-12 conferred verotoxicity on this nonpathogenic strain. Remarkably, cytotoxicity assay and immunoblot analysis showed, for the first time, an accumulation of the holotoxin complex in the periplasm of the wild-type strain and that a much smaller amount of StxA
1
and reduced verotoxicity were detected in the Δ
tatC
mutant cells. Together, these results establish that the TAT system of
E. coli
O157:H7 is an important virulence determinant of this enterohemorrhagic pathogen.
Mice Lacking Inducible Nitric Oxide Synthase Demonstrate Impaired Killing of
Porphyromonas gingivalis
Authors: Gyurko Robert , Boustany Gabriel , Huang Paul L. , Kantarci Alpdogan , Van Dyke Thomas E. , Genco Caroline A. , Gibson Frank C.
Published: August 2003

Porphyromonas gingivalis
is a primary etiological agent of generalized severe periodontitis, and emerging data suggest the importance of reactive oxygen and nitrogen species in periodontal tissue damage, as well as in microbial killing. Since nitric oxide (NO) released from inducible NO synthase (iNOS) has been shown to possess immunomodulatory, cytotoxic, and antibacterial effects in experimental models, we challenged iNOS-deficient (iNOS
−/−
) mice with
P. gingivalis
by using a subcutaneous chamber model to study the specific contribution of NO to host defense during
P. gingivalis
infection. iNOS
−/−
mice inoculated with
P. gingivalis
developed skin lesions and chamber rejection with higher frequency and to a greater degree than similarly challenged C57BL/6 wild-type (WT) mice. Chamber fluid from iNOS
−/−
mice possessed significantly more
P. gingivalis
than that of WT mice. The immunoglobulin G responses to
P. gingivalis
in serum was similar in WT and iNOS
−/−
mice, and the inductions of tumor necrosis factor alpha, interleukin-1β and interleukin-6, and prostaglandin E
2
were comparable between the two mouse strains. Although no differences in total leukocyte counts in chamber fluids were observed between iNOS
−/−
and WT mice, the percentage of dead polymorphonuclear leukocytes (PMNs) was significantly greater in iNOS
−/−
mouse chamber fluids than that of WT samples. Interestingly, casein-elicited PMNs from iNOS
−/−
mice released more superoxide than did WT PMNs when stimulated with
P. gingivalis
. These results indicate that modulation of superoxide levels is a mechanism by which NO influences PMN function and that NO is an important element of the host defense against
P. gingivalis
.
ZmpB, a Novel Virulence Factor ofStreptococcus pneumoniaeThat Induces Tumor Necrosis Factor Alpha Production in the Respiratory Tract
Authors: Blue C. E. , Paterson G. K. , Kerr A. R. , Bergé M. , Claverys J. P. , Mitchell T. J.
Published: August 2003

Inflammation is a prominent feature ofStreptococcus pneumoniaeinfection in both humans and animal models. Indeed, an intense host immune response to infection is thought to contribute significantly to the pathology of pneumococcal pneumonia and meningitis. Previously, induction of the inflammatory response following infection withS. pneumoniaehas been attributed to certain cell wall constituents and the toxin pneumolysin. Here we present data implicating a putative zinc metalloprotease, ZmpB, as having a role in inflammation. Null mutations were created in thezmpBgene of the virulent serotype 2 strain D39 and analyzed in a murine model of infection. Isogenic mutants were attenuated in pneumonia and septicemia models of infection, as determined by levels of bacteremia and murine survival. Mutants were not attenuated in colonization of murine airways or lung tissue. Examination of cytokine profiles within the lung tissue revealed significantly lower levels of the proinflammatory cytokine tumor necrosis factor alpha following challenge with theΔzmpBmutant (Δ739). These data identify ZmpB as a novel virulence factor capable of inducing inflammation in the lower respiratory tract. The possibility that ZmpB was involved in inhibition of complement activity was examined, but the data indicated that ZmpB does not have a significant effect on this important host defense. The regulation of ZmpB by a two-component system (TCS09) located immediately upstream of thezmpBgene was examined. TCS09 was not required for the expression ofzmpBduring exponential growth in vitro.
Bordetella pertussisAcquires Resistance to Complement-Mediated Killing In Vivo
Authors: Pishko Elizabeth J. , Betting David J. , Hutter Christina S. , Harvill Eric T.
Published: August 2003

In order to initially colonize a host, bacteria must avoid various components of the innate immune system, one of which is complement. The genusBordetellaincludes three closely related species that differ in their ability to resist complement-mediated killing.Bordetella parapertussisandBordetella bronchisepticaresist killing in naïve serum, a characteristic that may aid in efficient respiratory tract colonization and has been attributed to expression of O antigen.Bordetella pertussislacks O antigen and is sensitive to naïve serum in vitro, yet it also efficiently colonizes the respiratory tract. Based on these observations, we hypothesized thatB. pertussismay have an alternate mechanism to resist complement in vivo. While a number of reports on serum sensitivity of the bordetellae have been published, we show here that serum concentration and growth conditions can greatly alter the observed level of sensitivity to complement and that all but one strain ofB. pertussisobserved were sensitive to some level of naïve serum in vitro, particularly when there was excess complement. However,B. pertussisrapidly acquires increased resistance in vivo to naïve serum that is specific to the alternative pathway. Resistance is not efficiently acquired byB. parapertussisandB. bronchisepticamutants lacking O antigen. ThisB. pertussis-specific mechanism of complement resistance does not appear to be dependent on eitherbrkAor other genes expressed specifically in the Bvg+phase. This in vivo acquisition of alternative pathway resistance suggests that there is a novel O antigen-independent method by whichB. pertussisevades complement-mediated killing.