bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of a Semi-implicit Solver for Detailed Chemistry in Internal Combustion Engine Simulations
Authors: Liang Long , Kong Song-Charng , Jung Chulhwa , Reitz Rolf D.
Published: December 2006

An efficient semi-implicit numerical method is developed for solving the detailed chemical kinetic source terms in internal combustion (IC) engine simulations. The detailed chemistry system forms a group of coupled stiff ordinary differential equations (ODEs), which presents a very stringent time-step limitation when solved by standard explicit methods, and is computationally expensive when solved by iterative implicit methods. The present numerical solver uses a stiffly stable noniterative semi-implicit method. The formulation of numerical integration exploits the physical requirement that the species density and specific internal energy in the computational cells must be non-negative, so that the Lipschitz time-step constraint is not present and the computation time step can be orders of magnitude larger than that possible in standard explicit methods. The solver exploits the characteristics of the stiffness of the ODEs by using a sequential sort algorithm that ranks an approximation to the dominant eigenvalues of the system to achieve maximum accuracy. Subcycling within the chemistry solver routine is applied for each computational cell in engine simulations, where the subcycle time step is dynamically determined by monitoring the rate of change of concentration of key species, which have short characteristic time scales and are also important to the chemical heat release. The chemistry solver is applied in the KIVA-3V code to diesel engine simulations. Results are compared to those using the CHEMKIN package, which uses the VODE implicit solver. Good agreement was achieved for a wide range of engine operating conditions, and 40-70% CPU time savings were achieved by the present solver compared to the standard CHEMKIN.
A Bulk-Flow Model of Angled Injection Lomakin Bearings
Authors: Andrés Luis San , Soulas Thomas , Fayolle Patrice
Published: December 2006

This paper introduces a bulk-flow model for prediction of the static and dynamic force coefficients of angled injection Lomakin bearings. The analysis accounts for the flow interaction between the injection orifices, the supply circumferential groove, and the thin film lands. A one control-volume model in the groove is coupled to a bulk-flow model within the film lands of the bearing. Bernoulli-type relationships provide closure at the flow interfaces. Flow turbulence is accounted for with shear stress parameters and Moody’s friction factors. The flow equations are solved numerically using a robust computational method. Comparisons between predictions and experimental results for a tangential-against-rotation injection water Lomakin bearing show that novel model well predicts the leakage and direct stiffness and damping coefficients. Computed cross-coupled stiffness coefficients follow the experimental trends for increasing rotor speeds and supply pressures, but quantitative agreement remains poor. A parameter investigation shows evidence of the effects of the groove and land geometries on the Lomakin bearing flowrate and force coefficients. The orifice injection angle does not influence the bearing static performance, although it largely affects its stability characteristics through the evolution of the cross-coupled stiffnesses. The predictions confirm the promising stabilizing effect of the tangential-against-rotation injection configuration. Two design parameters, comprised of the feed orifices area and groove geometry, define the static and dynamic performance of Lomakin bearing. The analysis also shows that the film land clearance and length have a larger impact on the Lomakin bearing rotordynamic behavior than its groove depth and length.
Field Methods for Identification of Bearing Support Parameters—Part II: Identification From Rotor Dynamic Response due to Imbalances
Authors: De Santiago Oscar C. , San Andrés Luis
Published: December 2006

This paper describes a procedure suitable for field implementation that allows identification of synchronous bearing support parameters (force coefficients) from recorded rotor responses to imbalance. The experimental validation is conducted on a test rotor supported on two dissimilar bearing supports, both mechanically complex, each comprising a hydrodynamic film bearing in series with a squeeze film damper and elastic support structure. The identification procedure requires a minimum of two different imbalance distributions for identification of force coefficients from the two bearing supports. Presently, the test rotor responses show minimal cross-coupling effects, as also predicted by analysis, and the identification procedure disregards cross-coupled force coefficients thereby reducing its sensitivity to small variations in the measured response. The procedure renders satisfactory force coefficients in the speed range between 1500 and 3500rpm, enclosing the rotor-bearing system first critical speed. The identified direct force coefficients are in accordance with those derived from the impact load excitations presented in a companion paper.
Application of Controllable Electric Coolant Pump for Fuel Economy and Cooling Performance Improvement
Authors: Cho Hoon , Jung Dohoy , Filipi Zoran S. , Assanis Dennis N. , Vanderslice John , Bryzik Walter
Published: December 2006

The engine cooling system for a typical class 3 pickup truck with a medium duty diesel engine was modeled with a commercial code, GT-Cool, in order to explore the benefit of a controllable electric pump on the cooling performance and the pump operation. As the first step, the cooling system model with a conventional mechanical coolant pump was validated with experimental data. After the model validation, the mechanical pump submodel was replaced with the electric pump submodel, and then the potential benefit of the electric pump on fuel economy was investigated with the simulation. Based on coolant flow analysis, a modified thermostat hysteresis was proposed to reduce the recirculating flow and the electric pump effort. It was also demonstrated that the radiator size could be reduced without any cooling performance penalty by replacing the mechanical pump with the electric pump. The predicted results indicate that the cooling system with the electric pump can dramatically reduce the pump power consumption during the FTP 74 driving schedule and that the radiator can be downsized by more than 27% of the original size, under the grade load condition.
A Study of the Effects of Inlet Preswirl on the Dynamic Coefficients of a Straight-Bore Honeycomb Gas Damper Seal
Authors: Sprowl Tony B. , Childs Dara W.
Published: December 2006

Honeycomb seals are frequently used as replacements for labyrinth seals in high-pressure centrifugal compressors to enhance rotordynamic stability. A concern exists that this enhanced stability will be lost if the honeycomb cavities become clogged. Static and dynamic tests were conducted on a honeycomb and a smooth seal (representing the honeycomb seal with completely clogged cells) at the same constant clearances using air with a supply pressure of 70 bars. The test matrix included three speeds, three pressure ratios, and three inlet preswirl conditions. The results show increased leakage, decreased synchronous stiffness, and decreased dynamic stability for the smooth seal with preswirled flow. The results strongly support the use of swirl brakes at the entrance of a honeycomb seal if clogging is a concern. Comparisons between test results and predictions from a two-control-volume theory by Kleynhans and Childs showed excellent agreement in general.
Fuzzy Logic Estimation Applied to Newton Methods for Gas Turbines
Authors: Martis Dan
Published: December 2006

This method, based on fuzzy logic principles, is intended to find the most likely solution of an over-determined system, in specific conditions. The method addresses typical problems encountered in gas turbine performance analysis and, more specifically, to the alignment of a synthesis model with measured data. Generally speaking, the relatively low accuracy of measurements introduces a random noise around the true value of a performance parameter and distorts any deterministic solution of a square matrix-based linear system. The fuzzy logic estimator is able to get very close to the real solution by using additional (pseudo-redundant) parameters and by building the most likely solution based on each of the measurement accuracies. The accuracy—or “quality”—of a measurement is encapsulated within an extra dimension which is defined as fuzzy and which encompasses the whole range of values, between 0 (false) and 1 (true). The value of the method is shown in two examples. The first simulates compressor fouling, the other deals with actual engine test data following a hardware modification. Both examples experience noisy measurements. The method is stable and effective even at high level of noise. The results are within the close vicinity of the expected levels (within 0.2% accuracy) and the accuracy is about ten times lower than the noise level.
Operation of a Mesoscopic Gas Turbine Simulator at Speeds in Excess of 700,000rpm on Foil Bearings
Authors: Salehi Mohsen , Heshmat Hooshang , Walton James F. , Tomaszewski Michael
Published: December 2006

A small mesoscopic gas turbine engine (MGTE) simulator was tested at speeds over 700,000rpm. The MGTE was operated with specially designed miniature compliant foil journal and thrust air bearings. The operation of the simulator rotor and foil bearing system is a precursor to development of turbine powered micro-aerial vehicles and mesoscopic power generators. The foil bearings use a new fabrication technology in which each bearing is split. This feature permits the use of these bearings in highly advanced engines where single piece ceramic rotors may be required. The simulator weighed 56g (including the 9g rotor) and included two non-aerodynamic wheels to simulate the compressor and turbine wheels. Each compliant foil journal bearing had a diameter of 6mm and was located equidistant from each end of the rotor. Experimental work included operation of the simulator at speeds above 700,000rpm and at several different orientations including having the spin axis vertical. Results of the rotor bearing system dynamics are presented along with experimentally measured natural frequencies at many operating speeds. Good correlation between measurement and analysis is observed indicating the scalability of the analysis tools and hardware used. The rotor was very stable and well controlled throughout all testing conducted. Based on this successful testing it is expected that the goal of operating the rotor at speeds exceeding 1 million rpm will be achieved.
Gas Turbine Combustor Liner Life Assessment Using a Combined Fluid/Structural Approach
Authors: Tinga T. , van Kampen J. F. , de Jager B. , Kok J. B. W.
Published: December 2006

A life assessment was performed on a fighter jet engine annular combustor liner, using a combined fluid/structural approach. Computational fluid dynamics analyses were performed to obtain the thermal loading of the combustor liner and finite element analyses were done to calculate the temperature and stress/strain distribution in the liner during several operating conditions. A method was developed to analyze a complete flight with limited computational effort. Finally, the creep and fatigue life for a measured flight were calculated and the results were compared to field experience data. The absolute number of cycles to crack initiation appeared hard to predict, but the location and direction of cracking could be correlated well with field data.
Prediction of Engine Performance Under Compressor Inlet Flow Distortion Using Streamline Curvature
Authors: Pachidis Vassilios , Pilidis Pericles , Templalexis Ioannis , Korakianitis Theodosios , Kotsiopoulos Petros
Published: December 2006

Traditionally, engine performance has been simulated based on nondimensional maps for compressors and turbines. Component characteristic maps assume by default a given state of inlet conditions that cannot be easily altered in order to simulate two- or three-dimensional flow phenomena. Inlet flow distortion, for example, is usually simulated by applying empirical correction factors and modifiers to default component characteristics. Alternatively, the parallel compressor theory may be applied. The accuracy of the above methods has been rather questionable over the years since they are unable to capture in sufficient fidelity component-level, complex physical processes and analyze them in the context of the whole engine performance. The technique described in this paper integrates a zero-dimensional (nondimensional) gas turbine modelling and performance simulation system and a two-dimensional, streamline curvature compressor software. The two-dimensional compressor software can fully define the characteristics of any compressor at several operating conditions and is subsequently used in the zero-dimensional cycle analysis to provide a more accurate, physics-based estimate of compressor performance under clean and distorted inlet conditions, replacing the default compressor maps. The high-fidelity, two-dimensional compressor component communicates with the lower fidelity cycle via a fully automatic and iterative process for the determination of the correct operating point. This manuscript firstly gives a brief overview of the development, validation, and integration of the two-dimensional, streamline curvature compressor software with the low-fidelity cycle code. It also discusses the relative changes in the performance of a two-stage, experimental compressor with different types of radial pressure distortion obtained by running the two-dimensional streamline curvature compressor software independently. Moreover, the performance of a notional engine model, utilizing the coupled, two-dimensional compressor, under distorted conditions is discussed in detail and compared against the engine performance under clean conditions. In the cases examined, the analysis carried out by this study demonstrated relative changes in the simulated engine performance larger than 1%. This analysis proves the potential of the simulation strategy presented in this paper to investigate relevant physical processes occurring in an engine component in more detail, and to assess the effects of various isolated flow phenomena on overall engine performance in a timely and affordable manner. Moreover, in contrast to commercial computational fluid dynamics tools, this simulation strategy allows in-house empiricism and expertise to be incorporated in the flow-field calculations in the form of deviation and loss models.
Enhanced External Aerodynamic Performance of a Generic Combustor Using An Integrated OGV/Prediffuser Design Technique
Authors: Duncan Walker A. , Carrotte Jon F. , McGuirk James J.
Published: December 2006

In this paper we use experimental measurements to characterize the extent that improved the external aerodynamic performance (reduced total pressure loss, increased flow quality) of a gas-turbine combustion system may be achieved by adopting an integrated OGV/prediffuser technique. Two OGV/prediffuser combinations were tested. The first is a datum design corresponding to a conventional design approach, where the OGV and prediffuser are essentially designed in isolation. The second is an “integrated” design where the OGV blade shape has been modified, following recommendations of earlier CFD work (Final Report No. TT03R01, 2003), to produce a secondary flow/wake structure that allows the prediffuser to operate at a higher area ratio without boundary layer separation. This is demonstrated to increase static pressure recovery and reduce dump losses. Experimental measurements are presented on a fully annular rig. Several traverse planes are used to gather five-hole probe data that allow the flow structure through the OGV, at the inlet and exit of the prediffuser, and in the inner/outer annulus supply ducts to be examined. Both overall performance measures (loss coefficients) and measures of flow uniformity and quality are used to demonstrate that the integrated design is superior.
Stabilization of a Dynamic Walking Gait Simulation
Authors: Peasgood Mike , Kubica Eric , McPhee John
Published: December 2006

Forward dynamic simulations of human walking gait have typically simulated and analyzed a single step of the walking cycle, assuming symmetric and periodic gait. To enable simulations over many steps, a stabilizer is required to maintain the balance of the walking model, ideally mimicking the human balance control mechanism. This paper presents a feedback control system that stabilizes the torso orientation during a human walking gait dynamic simulation, enabling arbitrarily long simulations. The model is a two-dimensional mechanical simulation, in which the desired joint trajectories are defined as functions of time; the only external forces on the model are gravitational and ground reaction forces. Orientation or postural control is achieved by modulation of the rate at which lower limb joints move through angular trajectories. The controller design is based on a sequence of simple linear feedback controllers, each based on an intuitive control law. Controller parameters were determined iteratively using an optimization algorithm and repeated executions of the forward dynamics simulation to minimize control term errors. Results show the use of feedback control and joint speed modulation to be effective in maintaining balance for walking simulations of arbitrary length, allowing for analysis of steady-state walking.
A Fracture Mechanics Approach to the Prediction of Tool Wear in Dry High-Speed Machining of Aluminum Cast Alloys—Part 1: Model Development
Authors: Bardetsky Alexander , Attia Helmi , Elbestawi Mohamed
Published: January 2007

The utilization of cast aluminum alloys in automotive industry continues to rise because of consumer demand for a future generation of vehicles that will offer excellent fuel efficiency and emissions reduction, without compromising safety, performance, or comfort. Unlike wrought aluminum alloys, the cutting speed for cast aluminum alloys is considerably restricted due to the detrimental effect of the alloy’s silicon constituencies on tool life. In the present study, a new wear model is developed for tool-life management and enhancement, in a high-speed machining environment. The fracture-mechanics-based model requires normal and tangential stresses, acting on the flank of the cutting tool, as input data. Analysis of the subsurface crack propagation in the cobalt binder of cemented carbide cutting tool material is performed using a finite element (FE) model of the tool-workpiece sliding contact. The real microstructure of cemented carbide is incorporated into the FE model, and elastic-plastic properties of cobalt, defined by continuum theory of crystal plasticity are introduced. The estimation of the crack propagation rate is then used to predict the wear rate of the cutting tool. The model allows the microstructural characteristics of the cutting tool and workpiece material, as well as the tool’s loading conditions to be taken into consideration. Analysis of the results indicates that the interaction between the alloy’s hard silicon particles and the surface of the cutting tool is most detrimental to tool life. The fatigue wear of the cutting tool is shown to be directly proportional to the silicon content of the alloy, silicon grain size, and to the tool’s loading conditions.
Numerical Model of a Reciprocating Hydraulic Rod Seal
Authors: Salant Richard F. , Maser Nicholas , Yang Bo
Published: January 2007

A numerical model of an elastomeric reciprocating hydraulic rod seal has been constructed. The model consists of coupled fluid mechanics, deformation mechanics, and contact mechanics analyses, with an iterative computational procedure. The fluid mechanics analysis consists of the solution of the Reynolds equation, using flow factors to account for surface roughness. Deformation of the seal is computed through the use of influence coefficients, obtained from an off-line finite element analysis. The contact mechanics analysis uses the Greenwood and Williamson model. The seal model is used to predict leakage rate, friction force, fluid and contact pressure distributions, and film thickness distribution. Results for a typical seal show that the seal operates with mixed lubrication, and the seal roughness plays an important role in determining whether or not the seal leaks.
A Giant European Dinosaur and a New Sauropod Clade
Authors: Royo-Torres Rafael , Cobos Alberto , Alcalá Luis
Published: December 2006

Fossils of a giant sauropod dinosaur,
Turiasaurus riodevensis
, have been recovered from terrestrial deposits of the Villar del Arzobispo Formation (Jurassic-Cretaceous boundary) of Riodeva (Teruel Province, Spain). Its humerus length (1790 millimeters) and estimated mass (40 to 48 metric tons) indicate that it may have been the most massive terrestrial animal in Europe and one of the largest in the world. Phylogenetic analysis indicates that the fossil represents a member of a hitherto unrecognized group of primitive European eusauropods that evolved in the Jurassic.
Adjuvant-Enhanced Antibody Responses in the Absence of Toll-Like Receptor Signaling
Authors: Gavin Amanda L. , Hoebe Kasper , Duong Bao , Ota Takayuki , Martin Christopher , Beutler Bruce , Nemazee David
Published: December 2006

Innate immune signals mediated by Toll-like receptors (TLRs) have been thought to contribute considerably to the antibody-enhancing effects of vaccine adjuvants. However, we report here that mice deficient in the critical signaling components for TLR mount robust antibody responses to T cell–dependent antigen given in four typical adjuvants: alum, Freund's complete adjuvant, Freund's incomplete adjuvant, and monophosphoryl-lipid A/trehalose dicorynomycolate adjuvant. We conclude that TLR signaling does not account for the action of classical adjuvants and does not fully explain the action of a strong adjuvant containing a TLR ligand. This may have important implications in the use and development of vaccine adjuvants.
Master Class in Evolutionary Modeling
Authors: Frank Steven A.
Published: December 2006

Evolutionary Dynamics
. Exploring the Equations of Life.
By Martin A. Nowak
. Harvard University Press, Cambridge, MA, 2006. 377 pp. $35, £22.95, €32.30. ISBN 0-674-02338-2.

To further his case for studying living systems in the context of mathematical principles of evolutionary dynamics, the author presents a set of analytical tools and applies them to a range of illustrative problems.
Evaluation of a New Selective Chromogenic Agar Medium for Detection of Extended-Spectrum β-Lactamase-Producing
Enterobacteriaceae
Authors: Glupczynski Youri , Berhin Catherine , Bauraing Caroline , Bogaerts Pierre
Published: December 2006

A novel chromogenic agar medium (ESBL-Bx; bioMérieux, Marcy l'Etoile, France) was compared to MacConkey agar supplemented with 2 mg ceftazidime/liter (MCKC) for the selective isolation and presumptive identification of extended-spectrum β-lactamase (ESBL)-producing
Enterobacteriaceae
directly from clinical samples. Of a total of 644 clinical specimens (including 551 fecal samples), 496 yielded no growth and 148 yielded growth on one or both media. Overall, 44 ESBL-producing
Enterobacteriaceae
strains (
Escherichia coli
[
n
= 17],
Enterobacter aerogenes
[
n
= 17],
Klebsiella
spp. [
n
= 5], and
Citrobacter freundii
[
n
= 5]) were isolated from 37 specimens by a combination of both methods after 18 to 24 h of incubation. The sensitivities were 97.7 and 84.1% for ESBL-Bx and MCKC, respectively, with 43 ESBL-positive strains isolated as colored colonies from 36 specimens on ESBL-Bx versus 37 ESBL-positive organisms isolated from 32 specimens on MCKC. The specificities by specimens were 89 and 91% for ESBL-Bx and MCKC, respectively. On either one of the two media, natural AmpC-hyperproducing
Enterobacter
spp. (
n
= 25) and
Citrobacter
spp. (
n
= 14) were the most common false positives as well as non-ESBL-producing
Klebsiella oxytoca
(
n
= 18) on ESBL-Bx and
Morganella morganii
(
n
= 10) on MCKC. We conclude that ESBL-Bx is a sensitive and specific medium for the isolation of ESBL-producing
Enterobacteriaceae
from clinical samples. The main advantages of ESBL-Bx over MCKC reside in its chromogenic character and its sensitivity and selectivity, which enabled the recovery and presumptive identification of most ESBL-producing
Enterobacteriaceae
within 24 h and reduced by 27% the need for unnecessary identification and confirmation of ESBL testing when disregarding all colorless colonies growing on this medium.
Interaction of Rotavirus Polymerase VP1 with Nonstructural Protein NSP5 Is Stronger than That with NSP2
Authors: Arnoldi F. , Campagna M. , Eichwald C. , Desselberger U. , Burrone O. R.
Published: December 2006

Rotavirus morphogenesis starts in intracellular inclusion bodies called viroplasms. RNA replication and packaging are mediated by several viral proteins, of which VP1, the RNA-dependent RNA polymerase, and VP2, the core scaffolding protein, were shown to be sufficient to provide replicase activity in vitro. In vivo, however, viral replication complexes also contain the nonstructural proteins NSP2 and NSP5, which were shown to be essential for replication, to interact with each other, and to form viroplasm-like structures (VLS) when coexpressed in uninfected cells. In order to gain a better understanding of the intermediates formed during viral replication, this work focused on the interactions of NSP5 with VP1, VP2, and NSP2. We demonstrated a strong interaction of VP1 with NSP5 but only a weak one with NSP2 in cotransfected cells in the absence of other viral proteins or viral RNA. By contrast, we failed to coimmunoprecipitate VP2 with anti-NSP5 antibodies or NSP5 with anti-VP2 antibodies. We constructed a tagged form of VP1, which was found to colocalize in viroplasms and in VLS formed by NSP5 and NSP2. The tagged VP1 was able to replace VP1 structurally by being incorporated into progeny viral particles. When applying anti-tag-VP1 or anti-NSP5 antibodies, coimmunoprecipitation of tagged VP1 with NSP5 was found. Using deletion mutants of NSP5 or different fragments of NSP5 fused to enhanced green fluorescent protein, we identified the 48 C-terminal amino acids as the region essential for interaction with VP1.
Exceptional Flexibility in the Sequence Requirements for Coronavirus Small Envelope Protein Function
Authors: Kuo Lili , Hurst Kelley R. , Masters Paul S.
Published: December 2006

The small envelope protein (E) plays a role of central importance in the assembly of coronaviruses. This was initially established by studies demonstrating that cellular expression of only E protein and the membrane protein (M) was necessary and sufficient for the generation and release of virus-like particles. To investigate the role of E protein in the whole virus, we previously generated E gene mutants of mouse hepatitis virus (MHV) that were defective in viral growth and produced aberrantly assembled virions. Surprisingly, however, we were also able to isolate a viable MHV mutant (ΔE) in which the entire E gene, as well as the nonessential upstream genes 4 and 5a, were deleted. We have now constructed an E knockout mutant that confirms that the highly defective phenotype of the ΔE mutant is due to loss of the E gene. Additionally, we have created substitution mutants in which the MHV E gene was replaced by heterologous E genes from viruses spanning all three groups of the coronavirus family. Group 2 and 3 E proteins were readily exchangeable for that of MHV. However, the E protein of a group 1 coronavirus, transmissible gastroenteritis virus, became functional in MHV only after acquisition of particular mutations. Our results show that proteins encompassing a remarkably diverse range of primary amino acid sequences can provide E protein function in MHV. These findings suggest that E protein facilitates viral assembly in a manner that does not require E protein to make sequence-specific contacts with M protein.
Herpesvirus Saimiri STP-A Oncoprotein Utilizes Src Family Protein Tyrosine Kinase and Tumor Necrosis Factor Receptor-Associated Factors To Elicit Cellular Signal Transduction
Authors: Garcia Maria I. , Kaserman Joseph , Chung Young-Hwa , Jung Jae U. , Lee Sun-Hwa
Published: December 2006

The saimiri transforming protein oncogene, called STP-A, of herpesvirus saimiri (HVS) subgroup A is not required for viral replication but is required for lymphoid cell immortalization in culture and lymphoma induction in primates. Here we report that STP-A interacts with cellular tumor necrosis factor receptor-associated factors (TRAF2 and TRAF6) and Src family protein tyrosine kinases (SF-PTKs) in a genetically and functionally separable manner and that each interaction constitutively elicits independent cellular signal transduction. The amino-terminal and central proline-rich motifs of STP-A were responsible for TRAF6 and TRAF2 interactions, respectively, and STP-A and TRAF6 interaction contributed to the majority of NF-κB activation, whereas STP-A and TRAF2 interaction played a minor role in NF-κB activation. On the other hand, interaction of STP-A with SF-PTKs through its SH2 binding motif effectively elicited AP-1 and NF-AT transcription factor activity. One cellular gene targeted by STP-A is intercellular adhesion molecule 1 (ICAM-1), which participates in a wide range of inflammatory and immune responses. Both TRAF and SF-PTK signal transductions induced by STP-A were required for the marked increase of ICAM-1 expression. These results demonstrate that the viral oncogene STP-A independently targets two vital cellular signaling molecules and that these activities likely contribute to HVS-mediated lymphoid cell immortalization in culture and lymphoma induction in primates.
Changes in Paracrine Interleukin-2 Requirement, CCR7 Expression, Frequency, and Cytokine Secretion of Human Immunodeficiency Virus-Specific CD4+T Cells Are a Consequence of Antigen Load
Authors: Tilton John C. , Luskin Marlise R. , Johnson Alison J. , Manion Maura , Hallahan Claire W. , Metcalf Julia A. , McLaughlin Mary , Davey Richard T. , Connors Mark
Published: December 2006

Virus-specific CD4+T-cell responses are thought to be required for the induction and maintenance of many effective CD8+T-cell and B-cell immune responses in experimental animals and humans. Although the presence of human immunodeficiency virus (HIV)-specific CD4+T cells has been documented in patients at all stages of HIV infection, many fundamental questions regarding their frequency and function remain. A 10-color, 12-parameter flow cytometric panel was utilized to examine the frequency, memory phenotype (CD27, CCR7, and CD45RA), and cytokine production (interleukin-2 [IL-2], gamma interferon, and tumor necrosis factor alpha) of CD4+T cells specific for HIV antigens as well as for adenovirus, Epstein-Barr virus (EBV), influenza H1N1 virus, influenza H3N2 virus, cytomegalovirus, varicella-zoster virus (VZV), and tetanus toxoid in normal controls, long-term nonprogressors (LTNP), and HIV-infected patients with progressive disease on or off therapy. The HIV-specific CD4+T-cell responses in LTNP and patients on therapy were similar in frequency, phenotype, and cytokine production to responses directed against adenovirus, EBV, influenza virus, and VZV. HIV-specific CD4+T cells from patients off antiretroviral therapy demonstrated a shift towards a CCR7−CD45RA−phenotype and a reduced percentage of IL-2-producing cells. The alterations in cytokine production during HIV viremia were found to be intrinsic to the HIV-specific CD4+T cells and caused a requirement for IL-2 supplied exogenously for proliferation to occur. These observations suggest that many previously described changes in HIV-specific CD4+T-cell function and phenotype are a consequence of high levels of antigen in viremic patients. In addition, defects in function and phenotype of HIV-specific CD4+T cells are not readily discernible in the context of antiretroviral therapy but rather are similar to responses to other viruses.
CD8 T-Cell Recognition of Multiple Epitopes within Specific Gag Regions Is Associated with Maintenance of a Low Steady-State Viremia in Human Immunodeficiency Virus Type 1-Seropositive Patients
Authors: Geldmacher Christof , Currier Jeffrey R. , Herrmann Eva , Haule Antelmo , Kuta Ellen , McCutchan Francine , Njovu Lilian , Geis Steffen , Hoffmann Oliver , Maboko Leonard , Williamson Carolyn , Birx Deborah , Meyerhans Andreas , Cox Josephine , Hoelscher Michael
Published: December 2006

The importance of HLA class I-restricted CD8 T-cell responses in the control of human immunodeficiency virus (HIV) infection is generally accepted. While several studies have shown an association of certain HLA class I alleles with slower disease progression, it is not fully established whether this effect is mediated by HIV-specific CD8 T-cell responses restricted by these alleles. In order to study the influence of the HLA class I alleles on the HIV-specific CD8 T-cell response and on viral control, we have assessed HIV-specific epitope recognition, plasma viral load, and expression of HLA class I alleles in a cohort of HIV-seropositive bar workers. Possession of the HLA class I alleles B5801, B8101, and B0702 was associated with a low median viral load and simultaneously with a broader median recognition of Gag epitopes compared to all other HLA alleles (twofold increase) (P= 0.0035). We further found an inverse linear relationship between the number of Gag epitopes recognized and the plasma viral load (R= −0.36;P= 0.0016). Particularly, recognition of multiple epitopes within two regions of Gag (amino acids [aa] 1 to 75 and aa 248 to 500) was associated with the maintenance of a low steady-state viremia, even years after acute infection.
NS1 Proteins of Avian Influenza A Viruses Can Act as Antagonists of the Human Alpha/Beta Interferon Response
Authors: Hayman A. , Comely S. , Lackenby A. , Hartgroves L. C. S. , Goodbourn S. , McCauley J. W. , Barclay W. S.
Published: December 2006

Many viruses, including human influenza A virus, have developed strategies for counteracting the host type I interferon (IFN) response. We have explored whether avian influenza viruses were less capable of combating the type I IFN response in mammalian cells, as this might be a determinant of host range restriction. A panel of avian influenza viruses isolated between 1927 and 1997 was assembled. The selected viruses showed variation in their ability to activate the expression of a reporter gene under the control of the IFN-β promoter and in the levels of IFN induced in mammalian cells. Surprisingly, the avian NS1 proteins expressed alone or in the genetic background of a human influenza virus controlled IFN-β induction in a manner similar to the NS1 protein of human strains. There was no direct correlation between the IFN-β induction and replication of avian influenza viruses in human A549 cells. Nevertheless, human cells deficient in the type I IFN system showed enhanced replication of the avian viruses studied, implying that the human type I IFN response limits avian influenza viruses and can contribute to host range restriction.
Synergy of Small Molecular Inhibitors of Hepatitis C Virus Replication Directed at Multiple Viral Targets
Authors: Wyles David L. , Kaihara Kelly A. , Vaida Florin , Schooley Robert T.
Published: December 2006

Chronic hepatitis C virus (HCV) infection is a significant worldwide health problem with limited therapeutic options. A number of novel, small molecular inhibitors of HCV replication are now entering early clinical trials in humans. Resistance to small molecular inhibitors is likely to be a significant hurdle to their use in patients. A systematic assessment of combinations of interferon and/or novel anti-hepatitis C virus agents from several different mechanistic classes was performed in vitro. Combinations of inhibitors with different mechanisms of action consistently demonstrated more synergy than did compounds with similar mechanisms of action. These results suggest that combinations of inhibitors with different mechanisms of action should be prioritized for assessment in clinical trials for chronic hepatitis C virus infection.
Multiple Amino Acid Substitutions in Hemagglutinin Are Necessary for Wild-Type MeaslesVirus To Acquire the Ability To Use Receptor CD46 Efficiently
Authors: Tahara Maino , Takeda Makoto , Seki Fumio , Hashiguchi Takao , Yanagi Yusuke
Published: December 2006

Measles virus (MV) possesses two envelope glycoproteins, namely, the receptor-binding hemagglutinin (H) and fusion proteins. Wild-type MV strains isolated in B-lymphoid cell lines use signaling lymphocyte activation molecule (SLAM), but not CD46, as a cellular receptor, whereas MV vaccine strains of the Edmonston lineage use both SLAM and CD46 as receptors. Studies have shown that the residue at position 481 of the H protein is critical in determining the use of CD46 as a receptor. However, the wild-type IC-B strain with a single N481Y substitution in the H protein utilizes CD46 rather inefficiently. In this study, a number of chimeric and mutant H proteins, and recombinant viruses harboring them, were generated to determine which residues of the Edmonston H protein are responsible for its efficient use of CD46. Our results show that three substitutions (N390I and E492G plus N416D or T446S), in addition to N481Y, are necessary for the IC-B H protein to use CD46 efficiently as a receptor. The N390I, N416D, and T446S substitutions are present in the H proteins of all strains of the Edmonston lineage, whereas the E492G substitution is found only in the H protein of the Edmonston tag strain generated from cDNAs. The T484N substitution, found in some of the Edmonston-lineage strains, resulted in a similar effect on the use of CD46 to that caused by the E492G substitution. Thus, multiple residues in the H protein that have not previously been implicated have important roles in the interaction with CD46.
Non-operative breast pathology: lobular neoplasia
Authors: Reis-Filho Jorge S , Pinder Sarah E
Published: December 2006

Lobular neoplasia is a relatively uncommon lesion, which is frequently diagnosed in biopsy specimens taken for other reasons. Although the histological features of this lesion are well known, its biological significance as a “risk indicator” or “breast cancer precursor” has been a matter of debate. This review provides an update on recent clinicopathological and molecular data on lobular neoplasia and how these have changed the way these lesions are perceived and, most importantly, managed. Furthermore, the current recommendations for the management of lobular neoplasia diagnosed on core needle biopsies proposed in the National Health Service Breast Cancer Screening guidelines are discussed.
Group B streptococcus prevalence in pregnant women from North-Eastern Italy: advantages of a screening strategy based on direct plating plus broth enrichment
Authors: Busetti Marina , D’Agaro Pierlanfranco , Campello Cesare
Published: December 2006

Aims:

To assess the sensitivity of a combined selective broth enrichment technique plus selective plating for the detection of group B streptococcus (GBS) colonisation in a large cohort of pregnant women from North-Eastern Italy.

Methods:

During 2002–2005, 5020 pregnant women were screened between the 35th and the 37th week of gestation. A lower vaginal sample and a rectal sample were collected and inoculated onto LIM broth and a selective colistin aztreonam blood agar plate (CAP). Direct agar plates were examined after 18–24 hours and, if negative, after 48 hours. LIM broth was subcultured after 18–24 hours onto a Columbia blood agar plate. All colonies suggestive for GBS were submitted to phenotypic identification.

Results:

901 Women (17.9%) were positive for GBS. On 728 positive samples, corresponding to patients enrolled between 2003 and 2005, the results of selective direct plating and selective broth enrichment were compared. A total of 561 (77.1% of positive samples, corresponding to 13.9% of patients) were positive on direct selective agar; an additional 167 isolates (22.9% of samples, 4.1% of patients) were recovered from the LIM broth subculture.

Conclusions:

The prevalence of GBS carriage in this population-based study is a reliable estimate considering the sensitivity of the microbiological methods used, the rate of attendance of pregnant women to clinical and laboratory settings and the compliance to the protocol. Results confirm that the combination of selective enrichment broth and selective direct plating is a time-saving and sensitive method.
Selecting immunohistochemical cut-off scores for novel biomarkers of progression and survival in colorectal cancer
Authors: Zlobec Inti , Steele Russell , Terracciano Luigi , Jass Jeremy R , Lugli Alessandro
Published: December 2006

Background:

Cut-off scores for determining positivity of biomarkers detected by immunohistochemistry are often set arbitrarily and vary between reports.

Aims:

To evaluate the performance of receiver operating characteristic (ROC) curve analysis in determining clinically important cut-off scores for a novel tumour marker, the receptor for hyaluronic acid mediated motility (RHAMM), and show the reproducibility of the selected cut-off scores in 1197 mismatch-repair (MMR) proficient colorectal cancers (CRC).

Methods:

Immunohistochemistry for RHAMM was performed using a tissue microarray of 1197 MMR-proficient CRC. Immunoreactivity was scored using a semi-quantitative scoring method by evaluating the percentage of positive tumour cells. ROC curve analysis was performed for T stage, N stage, tumour grade, vascular invasion and survival. The score with the shortest distance from the curve to the point with both maximum sensitivity and specificity, i.e. the point (0.0, 1.0), was selected as the cut-off score leading to the greatest number of tumours correctly classified as having or not having the clinical outcome. In order to determine the reliability of the selected cut-off scores, 100 bootstrapped replications were performed to resample the data.

Results:

The cut-off score for T stage, N stage, tumour grade and vascular invasion was 100% and that for survival 90%. The most frequently selected cut-off score from the 100 resamples was also 100% for T stage, N stage, tumour grade, and vascular invasion and 90% for survival.

Conclusions:

ROC curve analysis can be used as an alternative method in the selection and validation of cut-off scores for determining the clinically relevant threshold for immunohistochemical tumour positivity.
Assessment of exposure to mercury from industrial emissions: comparing “distance as a proxy” and dispersion modelling approaches
Authors: Hodgson Susan , Nieuwenhuijsen Mark J , Colvile Roy , Jarup Lars
Published: December 2006

Background:The Runcorn area, north-west England, contains many pollution sources, the health effects of which have been under discussion for over 100 years. Preliminary investigations revealed an excess risk of mortality from kidney disease in people living nearest to several point sources of pollution, using distance as a proxy for exposure. Ongoing epidemiological investigations into the effect of ambient mercury exposure on dose and renal effect required a more refined assessment of exposure.

Methods:Atmospheric dispersion modelling was used to assess mercury dispersion from three mercury-emitting sources (including a large chlor alkali plant), based on knowledge of emissions, local meteorology and topography.

Results:The model was sensitive to various input parameters, with different dispersion patterns and ground-level concentrations, and therefore different exposed populations identified when different input parameters were defined. The different approaches to exposure assessment also had an impact on the epidemiological findings. The model output correlated well with weekly monitoring data collected in the local area, although the model underestimated concentrations in close proximity to the chlor alkali plant. The model identified that one point source did not contribute significantly to ground-level mercury concentrations, so that inclusion of this source when using the “distance as a proxy” approach led to significant exposure misclassification.

Conclusions:The model output indicates that assessment of ambient exposure should give consideration to the magnitude of emissions, point source characteristics, local meteorology and topography to ensure that the most appropriate exposure classification is reached. Even if dispersion modelling cannot be undertaken, these data can be used to inform and improve the distance as a proxy approach, and improve the interpretability of the epidemiological findings.
Causes of death among lead smelters in relation to the glucose-6-phosphate dehydrogenase polymorphism: Table 1
Authors: Cocco Pierluigi , Fadda Domenica , Atzeri Sergio , Avataneo Giuseppe , Meloni Michele , Flore Costantino
Published: December 2006

Objective:To assess, by updating a follow-up mortality study of a lead smelters cohort in Sardinia, Italy, the adverse health effects following occupational lead exposure in relation to the glucose-6-phosphate dehydrogenase (G6PD) polymorphism.

Method:The 1973–2003 mortality of 1017 male lead smelters were followed-up, divided into two subcohorts according to the G6PD phenotype: whether G6PD deficient (G6PD−) or wild-type (wtG6PD). Deaths observed in the overall cohort and the two subcohorts were compared with those expected, on the basis of the age-, sex- and calendar year-specific mortality in the general male population of the island. Directly standardised mortality rates (sr) in the two subcohorts were also compared.

Results:Cardiovascular mortality was strongly reduced among production and maintenance workers, which is most related to the healthy worker effect. However, the sr for cardiovascular diseases was substantially lower among the G6PD− subcohort (5.0×10−4) than among the wtG6PD subcohort (33.6×10−4; χ2 = 1.10; p = NS). Neoplasms of the haemopoietic system exceeded the expectation in the G6PD− subcohort (SMR = 388; 95% CI 111 to 1108). No other cancer sites showed any excess in the overall cohort or in the two subcohorts. No death from haemolytic anaemia occurred in the G6PD− subcohort.

Conclusion:With due consideration of the limited statistical power of our study, previous results suggesting that in workplaces where exposure is under careful control, expressing the G6PD− phenotype does not convey increased susceptibility to lead toxicity are confirmed. The observed excess risk of haematopoietic malignancies seems to have most likely resulted from chance.