bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of New PDC Bits for Drilling of Geothermal Wells—Part 1: Laboratory Testing
Authors: Karasawa H. , Misawa S.
Published: April 2008

Rock cutting, drilling and durability tests were conducted in order to obtain data to design polycrystalline diamond compact (PDC) bits for geothermal well drilling. Both conventional and new PDC bits with different rake angles were tested. The rock cutting tests revealed that cutting forces were minimized at −10 deg rake angle independent of rock type. In drilling and durability tests, a bit with backrake and siderake angles of −10 or −15 deg showed better performance concerning the penetration rate and the cutter strength. The new PDC bit exhibited better performance as compared to the conventional one, especially in hard rock drilling. Furthermore, a new PDC core bit (98.4 mm o. d., 66 mm i. d.) with eight cutters could be successfully applied to granite drilling equally as well as a bit with twelve cutters.
Scale Model Study of Pile Foundations Under Earthquake Excitation
Authors: Boyce L. , Kana D. D.
Published: April 2008

Similitude theory is used to develop scale models for determining the earthquake response of pile foundations embedded in overconsolidated clay. The model is compared with full-scale foundations embedded in natural soil, for which dynamic response measurements had been made in previous work. Correlation of the model and prototype earthquake response constitutes a major difference in this work over previous efforts using scale models. Gravity effects are included in the models by scaling pile and soil material properties. The model pile material is selected to provide the correctly scaled stiffness and mass properties. The required model soil properties are achieved by developing a mixture of bentonite, aerosil, and veegum. Elastic properties of the model soil are compared with those of the prototype by standard momotonic stress and cyclic stress soil tests. It is found that scaling considerations must also apply to supporting static soil tests for determining soil properties, as well as to the model piles for measurement of dynamic responses. Soil property nonlinearities are shown to be distorted by geometric effects. However, a method is developed to account for the distortion as long as excitation waveforms are similar. The successful correlation of pile data extends the relationship between frequency parameter and relative soil strain to much higher strain levels than those obtained in the prototype tests. Therefore, the potential for a significant savings in future investigative work is demonstrated with scale model testing.
Experimental Investigation of Capillary-Induced Rewetting in a Flat Porous Wicking Structure
Authors: Peterson G. P. , Peng X. F.
Published: April 2008

An experimental program was conducted to investigate the rewetting characteristics of liquid flowing through multiple layers of screen mesh covering a heated vertical plate. Data obtained for acetone and R-11 were analyzed and compared with previously developed theoretical expressions for the rewetting velocity, the maximum liquid rise height, and the maximum heat flux for which rewetting could occur. The experimental results indicate that the thickness of the screen mesh layer and the liquid thermophysical properties are the most important factors affecting the rewetting behavior. As predicted by the theoretical model, small increases in the thickness of the screen layer initially caused the maximum permissible rewetting heat flux to increase. Once the layer thickness had reached a critical value, continued increases resulted in a decrease in the maximum permissible rewetting heat flux.
An Experimental Investigation of the Blowout Limits of a Jet Diffusion Flame in Co-Flowing Streams of Different Velocity and Composition
Authors: Wierzba I. , Kar K. , Karim G. A.
Published: April 2008

The blowout limits of a methane diffusion flame in a co-flowing air-fuel or air-diluent stream were determined for a range of surrounding co-flow stream velocities, both laminar and turbulent, up to ~ 1.50 m/s. Methane, ethylene, propane and hydrogen were used as the fuels in the surrounding co-flow stream while nitrogen and carbon dioxide were used as diluents. The experimental results show that the velocity of the surrounding stream affects the blowout phenomena significantly. An increase in the stream velocity has a detrimental effect on the blowout limits at very low velocities up to 0.30 m/s (essentially laminar flow) and at velocities higher than 1.50 m/s (turbulent flow). The addition of a fuel to the air stream in most cases enhances the blowout limit of a methane diffusion flame. However, different trends in the variation of the blowout limits with the surrounding fuel concentration were observed, depending on the type of fuel used and on whether the surrounding coflow stream was laminar or turbulent. The addition of nitrogen or carbon dioxide to the air stream results in decreasing the blowout limits. The effect is more severe at the higher velocities.
Multiphase Flow Measurement Techniques—A Review
Authors: Rajan V. S. V. , Ridley R. K. , Rafa K. G.
Published: April 2008

This paper is a review of current techniques available for measuring the velocity and composition in multiphase streams, to obtain the mass flow rate of the individual phases. An extensive literature search was conducted on the topic and related areas of interest. The major difficulty in measuring both the velocity and composition of multiphase streams is in dealing with the wide variety of flow regimes which are possible in multiphase flow in pipes. A device which is suitable for accurate velocity measurement in multiphase flows is not commercially available. However, if the flow is well mixed, it should be possible to calibrate a simple device, such as a nozzle or a venturi, to provide accurate total volumetric flow rates. Several commercial in-line static mixing devices are suitable for low gas concentrations (≤ 10 percent) and with superficial gas velocities higher than 10 m/s. For lower gas velocities and high gas concentrations, the suitability of these in-line mixers will have to be further assessed experimentally. Other techniques such as cross-correlation are known for two-phase flow velocity measurements, and the results of these applications look promising. A multiphase compositional meter to monitor the concentration of oil, water, and gas phases flowing in a pipeline, used in combination with a suitable homogenizer and a velocity meter, would facilitate measurement of the mass flow rates of the individual phases. Further work must be done to develop this concept.
Entropy Generation Rate in a Chemically Reacting
System
Authors: Gyftopoulos E. P. , Beretta G. P.
Published: April 2008

For a nonchemical-equilibrium state of an isolated system A that has r constituents with initial amounts na = {n1a, n2a, …, nra}, and that is subject to τ chemical reaction mechanisms, temperature, pressure, and chemical potentials cannot be defined. As time evolves, the values of the amounts of constitutents vary according to the stoichiometric relations ni(t) = nia + Σj=1τ νi(j) εj(t), where νi(j) is the stoichiometric coefficient of the ith constituent in the j-reaction mechanism and εj(t) the reaction coordinate of the jth reaction at time t. For such a state, we approximate the values of all the properties at time t with the corresponding properties of the stable equilibrium state of a surrogate system B consisting of the same constituents as A with amounts equal to ni(t) for i = 1, 2, …, r, but experiencing no chemical reactions. Under this approximation, the rate of entropy generation is given by the expression S˙irr = ε˙ · Y, where ε˙ is the row vector of the τ rates of change of the reaction coordinates, ε˙ = { ε˙1, …, ε˙τ }, Y the column vector of the τ ratios aj/Toff for j = 1, 2, …, τ, aj = −Σi=1r νi(j) μi,off, that is, the jth affinity of the stable equilibrium state of the surrogate system B, and μi,off, and Toff are the chemical potential of the ith constituent and the temperature of the stable equilibrium state of the surrogate system. Under the same approximation, by further assuming that ε˙ can be represented as a function of Y only that is, ε˙(Y), with ε˙(0) = 0 for chemical equilibrium, we show that ε˙ = L·Y + (higher order terms in Y), where L is a τ × τ matrix that must be non-negative definite and symmetric, that is, such that the matrix elements Lij satisfy the Onsager reciprocal relations, Lij = Lji. It is noteworthy that, for the first time, the Onsager relations are proven without reference to microscopic reversibility. In our view, if a process is irreversible, microscopic reversibility does not exist.
Optimum Efficiencies and Phase Change Temperatures in Latent Heat Storage Systems
Authors: Aceves-Saborio S. , Nakamura H. , Reistad G. M.
Published: April 2008

This paper presents an analysis of a class of latent heat storage systems (LHSS). The analysis is based on a lumped model (the basic model) that allows a broad class of LHSSs to be completely specified, with only two parameters and a set of operating temperatures, while still retaining the main thermodynamic aspects associated with its operation. Characterization of the performance in this manner permits the broad base application potential of such systems to be viewed. This modeling is in contrast to most studies to date, which employ many parameters to include details of specific systems, and therefore obscure, to a great extent, this broad-based application potential. The basic model is later modified in three ways to analyze operating conditions that either occur in practical units or are desirable for an improved operation of the units. The modifications include, first, the consideration of the LHSS as being formed by many independent phase-change material (PCM) capsules. Second, the possibility of having PCMs with different phase change temperatures filling the capsules. Third, the case when the PCM melts over a temperature range. The results indicate that the efficiency of the basic model represents a higher bound for the efficient operation of LHSSs with negligible sensible storage capacity, and a single PCM. Using multiple PCMs within a LHSS results in higher efficiencies. These efficiencies set higher bounds for efficiency of any sensible or latent heat storage system, and also represent the only possibility for reversible operation of LHSS.
Minimum-Cost Well Drilling Strategy Using Dynamic Programming
Authors: Wojtanowicz A. K. , Kuru E.
Published: April 2008

This paper presents an advanced concept in drilling optimization—the dynamic drilling strategy. The dynamic drilling strategy is a new methodology of drilling process planning and control; it combines theory of single-bit control with an optimal multi-bit drilling program for a well. In the simulation study, the dynamic drilling strategy was compared to conventional drilling optimization and typical field practices; the considerable cost-saving potential of 25 and 60 percent, respectively, was estimated. The method also appeared to be the most cost-effective for expensive and long-lasting PDC bits through better utilization of their performance and reduction in the number of bits needed for the hole.
An Experimental Verification of a Conceptual Heat-Pipe Radiator
Authors: Ravigururajan T. S. , Goryca M. L.
Published: April 2008

The radiator and its vulnerability to damage is one of the main criteria in automotive design. This study employed heat pipes in simulated radiators to transfer waste heat to the surrounding environment. A small-scale heat-pipe radiator module was designed using a computer program. Experimental tests were performed on this module to validate the design methodology and to study the vulnerability characteristics. The tests were conducted for a wide range of operating parameters such as air velocity, coolant flow rates, and the number of heat pipes damaged. The study indicated that a heat-pipe radiator may provide the necessary “limp home” capability to a vehicle, even with 50 percent of the pipes damaged. Also, with the radiators operating at less than peak load (slower vehicle speed), the undamaged heat pipes substantially compensated for the damaged heat pipes, adding to the reliability of the system.
Analytical and Experimental Investigation of Entrainment in Capillary Pumped Wicking Structures
Authors: Kim B. H. , Peterson G. P. , Kihm K. D.
Published: April 2008

Analytical and experimental investigations were conducted to identify and better understand the parameters that govern the entrainment of liquid droplets in high-velocity gas streams flowing over capillary wicking structures. Using a flow visualization technique, two modes of entrainment were identified and described for high-velocity gas flows over an intermittently interrupted liquid surface. These two modes, roll-wave entrainment and stripping entrainment, were found to correspond to the lower and upper critical gas velocities, respectively. Measurements of the critical gas velocities and the droplet size distribution (Sauter mean diameter) of the entrained sprays were made as a function of the capillary pore size for three different mesh sizes and were compared with several analytical models developed in previous investigations. The flow visualization results indicate that the upper critical velocity is insensitive to variations in the capillary pumping rate provided the capillary pores are properly primed. The experimental results also indicate that the critical velocity for a given mesh is strongly influenced by the mesh dimensions, but that the previously developed criteria for estimating the critical velocity results in an underestimation of the upper critical velocity for all but very small pore sizes. Finally, to resolve this problem a new analytical model for predicting the critical velocity was developed and shown to be accurate for a wide range of capillary pore sizes.
A Correlation for the Heat Conduction Effects in Counterflow Rotary Regenerative Heat Exchangers
Authors: Shen C. M. , Worek W. M.
Published: April 2008

Equations that predict the dependence of regenerator effectiveness on heat conduction in the matrix both parallel to and perpendicular to the fluid flow are derived from numerical simulations. The equations developed use Biot numbers parallel to the direction of fluid flow (Bix) and perpendicular to the fluid flow direction (Biy), the ratio of heat capacity rates (C*), the heat capacity rate ratio (C*Γ), and the overall number of transfer units (NTUo) to characterize the regenerator performance. Comparison of numerical predictions with those obtained using the equations developed in this paper show excellent agreement. These equations enable designers to accurately account for two-dimensional conduction effects when regenerators are designed.
A Kinetic Investigation of the Oxidation of Low Heating Value Fuel Mixtures of Methane and Diluents
Authors: Karim G. A. , Hanati A. S. , Zhou G.
Published: April 2008

The thermodynamics and chemical kinetics of the combustion in air of methane when containing varying concentrations of the common diluents CO2, N2, and H2O are considered over a wide range of composition, temperature and pressure. Some approaches are then suggested towards enhancing the combustion rate of such mixtures in air.
Design of Laminated Composite Plates for Maximum Shear Buckling Loads
Authors: Chang R. R. , Chu K. H. , Kam T. Y.
Published: April 2008

The optimal lamination arrangements of laminated composite plates with maximum shear buckling loads are studied via a multi-start global optimization technique. A previously proposed shear deformable finite element is used to evaluate the positive and negative shear buckling loads of laminated composite plates in the optimal design process. Optimal lay-ups of thin as well as moderately thick composite plates with global maximum positive or negative shear buckling loads are determined utilizing the multi-start global optimal design technique. A number of examples of the optimal shear buckling design of symmetrically and antisymmetrically laminated composite plates with various material properties, length-to-thickness ratios, aspect ratios and different numbers of layer gorups are given to illustrate the trends of optimal layer orientations of the plates. Since the existence of in-plane axial forces is possible, the effects of axial compressive load on the optimal layer orientations for maximum shear buckling load are also investigated.
Tribological Performance Evaluation of Oil Mist Lubrication
Authors: Shamim A. , Kettleborough C. F.
Published: April 2008

In this research work, the tribological performance of oil mist lubrication (pure mist), as applied to rolling element bearings, was investigated. In the first part of this research, tests were conducted to compare the performances of oil mist and conventional oil sump lubrication in terms of operating temperature and friction with variation of load and speed. In the second part, the two methods of lubrication were compared directly under endurance test conditions. The oil mist lubricated high-precision angular contact test bearings ran cooler by about 10°C. Also, the oil mist lubricated bearings had about 25 percent less friction. In the third part, endurance tests were conducted to investigate the influence of oil mist lubrication on the life of rolling element bearings. Weibull and maximum likelihood analysis of the endurance test data indicated that, in addition to savings in energy, oil mist lubrication provides better wear and fatigue protection to the test bearings compared to conventional sump lubrication.
3-D Stress Analysis of Cross-Ply Laminated Composites
Authors: Chao C. C. , Tung T. P. , Li H. H.
Published: April 2008

A consistent higher-order theory is presented for static deformation and stress analysis of cross-ply thick laminates. Emphasis is placed on consistence with the 3-D boundary conditions and interlaminar stress continuity, exterior and interior, respectively, to the simply supported rectangular plate. All edges and lateral surfaces are considered stress-free, while surface traction and applied load equilibrium is maintained in the loading area. Individual layer displacement fields are expressed in terms of in-plane double Fourier series and cubic polynomials in thickness coordinates with continuity of interlaminar displacements and transverse stresses observed. A system of equations is derived with all these necessary conditions satisfied by means of the higher-order terms of the displacement fields in the extended Rayleigh-Ritz procedure. 3-D displacement and stress components, as compared well with exact solution cases available, can be found throughout the plate for 3-D analysis of localized damage. Thickness shrinking is noted with no mid-surface symmetry of stress distribution.
Toward a lateral carbon nanotube based field emission triode
Authors: Monica A. H. , Paranjape M. , Coles G. L. , Papadakis S. J. , Osiander R.
Published: April 2008

In this study, a method of fabricating lateral carbon nanotube (CNT)-based field emission triodes is discussed. The device, tested here in a diode configuration, consists of CNT emitters grown laterally from an etched quartz sidewall using thermal chemical vapor deposition. The lateral CNT growth is facilitated by a novel two-step angled evaporation technique. This method allows a Ni catalyst to be selectively deposited along the cathodic sidewall while burying all other regions of exposed Ni in a thick Ti layer thus preventing unwanted CNT growth. The lateral CNT emitters demonstrated turn-on fields as low as ∼1.2 V∕μm for a total anode current of ∼10 nA. The CNT emitters, with an estimated emitting area of 3.8×10−6 cm2, achieved a current of ∼3.0 μA at an applied field of ∼2.0 V∕μm corresponding to a current density of approximately 800 mA∕cm2. The temperature dependence of the emission is also investigated.
Modification of the field enhancement factor for a field emitter with a surrounding electrode stabilized using a field effect transistor
Authors: Neo Yoichiro , Matsumoto Takahiro , Shimawaki Hidetaka , Mimura Hidenori , Yokoo Kuniyoshi
Published: April 2008

One of the useful methods for stabilizing field emission current in field emitter arrays (FEAs) is to control them using field effect transistors (FETs) connected in series. However, one cannot use conventional FETs, because the electron extraction voltage (typically hundreds of volts) of FEAs is much higher than the permitted source-drain voltage of FETs. The authors conducted a detailed investigation of the mechanism for current stabilization of the field emission current while controlling the field emitter tip wtih a FET. The electron source consists of the FET controlled tip and surrounding electrode, which is kept at a constant potential. In this paper the authors discuss how the field enhancement factor (β) is modified by the potential distribution, which is determined by the potentials of the tip and the surrounding electrode, Making use of this effect, the authors could control a FEA that has a high electron extraction voltage with a FET with a lower source-drain voltage.
Fitting nonlinear Fowler-Nordheim plots of field emission strips with a self-consistent parallel plane model
Authors: Lin Ming-Chieh , Liao Yi-Huan
Published: April 2008

The saturation behavior of field emission strips is investigated by using a finite-difference time-domain (FDTD) particle-in-cell (PIC) simulation. The field-emission process is described quantum mechanically by the Fowler-Nordheim (FN) equation. Space charge effects are automatically included in the FDTD PIC simulations. The simulation results have confirmed that the saturation is caused by the space charge effects. A self-consistent parallel plane (SCPP) model has been developed for fitting the nonlinear FN plots of field emission strips. Within the framework of an effective work function approximation and energy conservation, the FN and Poisson’s equations are solved self-consistently in the SCPP model. It is demonstrated that the nonlinear FN plots of the field emission strips can be fitted by the SCPP model very well. The electric properties of the field emission strips can be characterized by the effective work function and the effective emission area. In addition, the field emission of Spindt-type cathodes may be possibly fitted with the SCPP model as well as the field emission strips.
Ta nanotubes grown by glancing angle deposition
Authors: Kesapragada S. V. , Sotherland P. R. , Gall D.
Published: April 2008

Regular arrays of vertical 200-nm-diameter hollow Ta tubes were grown by glancing angle deposition (GLAD) onto Cr nanoring patterns that were fabricated by positive-resist e-beam lithography followed by nondirectional Cr deposition and a lift-off process. During GLAD, nanorods nucleate around the edges of the patterned rings, broaden, and merge to form tubes with 50-nm-thick walls. The nanotubes remain open during continued growth, with a slight (13%) decrease in the effective inner diameter for an increasing tube height from 200 to 600 nm. These results demonstrate that complex patterned two-dimensional shapes can be extended into the third dimension using the GLAD process.
Electrical properties of conductive and resistive ZnSe layers
Authors: Oh D. C. , Im I. H. , Park S. H. , Hanada T. , Yao T. , Song J. S. , Chang J. H. , Makino H. , Han C. S. , Koo K. H.
Published: April 2008

The authors have investigated the electrical properties for one typical set of Al-doped ZnSe layers: one is conductive (type I) and the other is resistive (type II). The two types of ZnSe:Al layers are grown on different substrates by molecular-beam epitaxy under the same conditions: type I is on a 15° tilted (001) GaAs substrate and type II is on an exact (001) substrate. In capacitance-voltage curves, it is found that the measured capacitance in type II is 20 times smaller than that of type I. Moreover, it is estimated that the net-doping density of type II (∼1015cm−3) is two orders of magnitude lower than that of type I (∼1017cm−3). Frequency-dependence measurements of capacitance indicate that type II suffers from deep levels more seriously than type I. In photoluminescence spectra, it is shown that strong deep-level emission peaks exist at the energies of 2.03 and 2.24eV, but their emission features are almost the same in types I and II. In photocapacitance spectra, it is found that electron-trap centers exist in the midgap region, located at 1.1, 1.2, and 1.3eV below the conduction-band minimum, and the photocapacitance generated in the midgap of type II is seven times larger than that of type I. Moreover, it is estimated that the total density of the three trap centers in type II (∼1017cm−3) is similar to the net-doping density of type I. Consequently, it is suggested that the midgap trap centers contribute to the carrier compensation in ZnSe:Al layers and induce the different electrical properties in types I and II.
Deep-UV exposure of poly(methyl methacrylate) at 254 nm using low-pressure mercury vapor lamps
Authors: Johnstone Robert W. , Foulds Ian G. , Parameswaran M.
Published: April 2008

Poly(methyl methacrylate) (PMMA) is a transparent thermoplastic with important applications as a positive resist for various radiation sources. When used as a photoresist, PMMA is typically used with wavelengths shorter than 240 nm, as that is the commonly accepted upper limit of effectiveness. However, the authors have shown patterning of nonamplified PMMA films at 254 nm, which is significant because 254 nm radiation can be produced using inexpensive low-pressure mercury vapor lamps. Data for the etch depth as a function of exposure dose (0–12 h), developer temperature (20–35 °C), and etch time were collected. Dissolution rates of up to many microns a minute are possible, and the dissolution rate ratio of exposed over unexposed PMMA can reach over 3000. This demonstrates the feasibility of PMMA exposure using deep-UV at 254 nm.
Optimization of electrical characteristics of gadolinium (Gd2O3) incorporated HfO2 GaAs n-type metal-oxide semiconductor capacitors with silicon-interface-passivation layer
Authors: Park Sung Il , Ok Injo , Kim Hyoung-Sub , Zhu Feng , Zhang Manhong , Yum Jung Hwan , Han Zhao , Lee Jack C.
Published: April 2008

The electrical characteristics of Gd2O3-incorporated HfO2 multimetal dielectric n-type doped gallium arsenide (GaAs) metal-oxide semiconductor capacitors with different Gd2O3 and HfO2 thicknesses are investigated. A top Gd2O3 with bottom HfO2 bilayer dielectric shows excellent capacitance-voltage (C-V) characteristics and the lowest hysteresis. Scaling down of this Gd2O3∕HfO2 dielectric results in substantial reduction in hysteresis compared to HfO2 without significant change in equivalent oxide thickness. A qualitative explanation of reduced hysteresis with an electric field model is presented.
Electron optics of microlenses with inclined beams
Authors: Zhang Y. , Barth J. E. , Kruit P.
Published: April 2008

For multielectron beam systems with a single electron source, the outside beams need to be collimated before entering the individual microcolumns. As an alternative of the traditional multibeam source design where the broad beam from the source is collimated by a single lens, the broad beam can be first split in subbeams that are focused by a microlens array and subsequently collimated by a deflector array. This configuration avoids the large angular error due to spherical and chromatic aberration of the collimator lens. The electron optics of the microlenses that are focusing skewed beams is investigated for different lens types and geometries. A two-electrode immersion microlens array with offset apertures is a good candidate due to its small off-axial aberrations. A 100-beam source unit, comprising a Schottky emitter, an immersion microlens array, and a deflector array, is capable of generating 100 parallel beamlets with beamlet current of 2nA.
Wnt5a Control of Cell Polarity and Directional Movement by Polarized Redistribution of Adhesion Receptors
Authors: Witze Eric S. , Litman Elizabeth S. , Argast Gretchen M. , Moon Randall T. , Ahn Natalie G.
Published: April 2008

Mechanisms by which Wnt pathways integrate the organization of receptors, organelles, and cytoskeletal proteins to confer cell polarity and directional cell movement are incompletely understood. We show that acute responses to Wnt5a involve recruitment of actin, myosin IIB, Frizzled 3, and melanoma cell adhesion molecule into an intracellular structure in a melanoma cell line. In the presence of a chemokine gradient, this Wnt-mediated receptor–actin–myosin polarity (W-RAMP) structure accumulates asymmetrically at the cell periphery, where it triggers membrane contractility and nuclear movement in the direction of membrane retraction. The process requires endosome trafficking, is associated with multivesicular bodies, and is regulated by Wnt5a through the small guanosine triphosphatases Rab4 and RhoB. Thus, cell-autonomous mechanisms allow Wnt5a to control cell orientation, polarity, and directional movement in response to positional cues from chemokine gradients.
The Global Circulation of Seasonal Influenza A (H3N2) Viruses
Authors: Russell Colin A. , Jones Terry C. , Barr Ian G. , Cox Nancy J. , Garten Rebecca J. , Gregory Vicky , Gust Ian D. , Hampson Alan W. , Hay Alan J. , Hurt Aeron C. , de Jong Jan C. , Kelso Anne , Klimov Alexander I. , Kageyama Tsutomu , Komadina Naomi , Lapedes Alan S. , Lin Yi P. , Mosterin Ana , Obuchi Masatsugu , Odagiri Takato , Osterhaus Albert D. M. E. , Rimmelzwaan Guus F. , Shaw Michael W. , Skepner Eugene , Stohr Klaus , Tashiro Masato , Fouchier Ron A. M. , Smith Derek J.
Published: April 2008

Antigenic and genetic analysis of the hemagglutinin of â¼13,000 human influenza A (H3N2) viruses from six continents during 2002â2007 revealed that there was continuous circulation in east and Southeast Asia (E-SE Asia) via a region-wide network of temporally overlapping epidemics and that epidemics in the temperate regions were seeded from this network each year. Seed strains generally first reached Oceania, North America, and Europe, and later South America. This evidence suggests that once A (H3N2) viruses leave E-SE Asia, they are unlikely to contribute to long-term viral evolution. If the trends observed during this period are an accurate representation of overall patterns of spread, then the antigenic characteristics of A (H3N2) viruses outside E-SE Asia may be forecast each year based on surveillance within E-SE Asia, with consequent improvements to vaccine strain selection.
Recapitulation of IVIG Anti-Inflammatory Activity with a Recombinant IgG Fc
Authors: Anthony Robert M. , Nimmerjahn Falk , Ashline David J. , Reinhold Vernon N. , Paulson James C. , Ravetch Jeffrey V.
Published: April 2008

It is well established that high doses of monomeric immunoglobulin G (IgG) purified from pooled human plasma [intravenous immunoglobulin (IVIG)] confer anti-inflammatory activity in a variety of autoimmune settings. However, exactly how those effects are mediated is not clear because of the heterogeneity of IVIG. Recent studies have demonstrated that the anti-inflammatory activity of IgG is completely dependent on sialylation of the N-linked glycan of the IgG Fc fragment. Here we determine the precise glycan requirements for this anti-inflammatory activity, allowing us to engineer an appropriate IgG1 Fc fragment, and thus generate a fully recombinant, sialylated IgG1 Fc with greatly enhanced potency. This therapeutic molecule precisely defines the biologically active component of IVIG and helps guide development of an IVIG replacement with improved activity and availability.
Significantly Improved Accuracy of Diagnosis of Early Lyme Disease by Peptide Enzyme-Linked Immunosorbent Assay Based on the Borreliacidal Antibody Epitope of
Borrelia burgdorferi
OspC
Authors: Jobe Dean A. , Lovrich Steven D. , Asp Krista E. , Mathiason Michelle A. , Albrecht Stephanie E. , Schell Ronald F. , Callister Steven M.
Published: April 2008

Highly specific borreliacidal antibodies are induced by infection with
Borrelia burgdorferi
, and the immunodominant response during early Lyme disease is specific for an epitope within the 7 amino acids nearest the C terminus of OspC. We evaluated the ability of an enzyme-linked immunosorbent assay (ELISA) based on a synthetic peptide (OspC7) that matched the region to detect the response and compared the sensitivity during early Lyme disease to that for an FDA-approved Western blot. When the optical density value was adjusted to 98% specificity based on the results from testing normal or uncharacterized sera (
n
= 236) or sera from patients with blood factors or illnesses that commonly produce antibodies that cross-react with
B. burgdorferi
antigens (
n
= 77), 115 (73%) of 157 sera from patients likely to have early Lyme disease were positive for immunoglobulin M (IgM) antibodies and 17 (11%) also had IgG antibodies. In addition, the IgM ELISA reactivities and the titers of antibodies detected by a flow cytometric borreliacidal antibody test correlated closely (
r
= 0.646). Moreover, the IgM ELISA was significantly more sensitive (
P
< 0.001) than the Western blot procedure. The findings therefore confirmed that the peptide IgM ELISA detected OspC borreliacidal antibodies and provided strong evidence that the test can eliminate the necessity for confirming early Lyme disease by a supplementary test such as Western blotting.
Sequence Type and
emm
Type Diversity in
Streptococcus pyogenes
Isolates Causing Invasive Disease in Norway between 1988 and 2003
Authors: Meisal Roger , Høiby E. Arne , Aaberge Ingeborg S. , Caugant Dominique A.
Published: April 2008

The incidence of invasive group A streptococcal disease has increased in Norway since the 1980s. Analysis of 100 isolates recovered from 1988 to 2003 showed an increased genotypic diversity over time, while the prevalence of the strain that dominated in 1988, sequence type (ST)-28/
emm
-1, decreased. Necrotizing fasciitis was often associated with ST-15/
emm
-3.
Norovirus Excretion in an Aged-Care Setting
Authors: Tu Elise T.-V. , Bull Rowena A. , Kim Mi-Jurng , McIver Christopher J. , Heron Leon , Rawlinson William D. , White Peter A.
Published: April 2008

Norovirus genogroup II excretion during an outbreak of gastroenteritis was investigated in an aged-care facility. Viral shedding peaked in the acute stage of illness and continued for an average of 28.7 days. The viral decay rate was 0.76 per day, which corresponds to a viral half-life of 2.5 days.
RUNX1 Permits E4orf6-Directed Nuclear Localization of the Adenovirus E1B-55K Protein and Associates with Centers of Viral DNA and RNA Synthesis
Authors: Marshall Leslie J. , Moore Amy C. , Ohki Misao , Kitabayashi Issay , Patterson David , Ornelles David A.
Published: April 2008

The localization of the adenovirus E1B-55K-E4orf6 protein complex is critical for its function. Prior studies demonstrated that E4orf6 directs the nuclear localization of E1B-55K in human cells and in rodent cells that contain part of human chromosome 21. We show here that the relevant activity on chromosome 21 maps to
RUNX1
. RUNX1 proteins are transcription factors that serve as scaffolds for the assembly of proteins that regulate transcription and RNA processing. After transfection, the RUNX1a, RUNX1b, and RUNX1-ΔN variants allowed E4orf6-directed E1B-55K nuclear localization. The failure of RUNX1c to allow nuclear colocalization was relieved by the deletion of amino-terminal residues of this protein. In the adenovirus-infected mouse cell, RUNX1 proteins were localized to discrete structures about the periphery of viral replication centers. These sites are enriched in viral RNA and RNA-processing factors. RUNX1b and RUNX1a proteins displaced E4orf6 from these sites. The association of E1B-55K at viral replication centers was enhanced by the RUNX1a and RUNX1b proteins, but only in the absence of E4orf6. In the presence of E4orf6, E1B-55K occurred in a perinuclear cytoplasmic body resembling the aggresome and was excluded from the nucleus of the infected mouse cell. We interpret these findings to mean that a dynamic relationship exists between the E4orf6, E1B-55K, and RUNX1 proteins. In cooperation with E4orf6, RUNX1 proteins are able to modulate the localization of E1B-55K and even remodel virus-specific structures that form at late times of infection. Subsequent studies will need to determine a functional consequence of the interaction between E4orf6, E1B-55K, and RUNX1.
Porcine Rotavirus Bearing an Aberrant Gene Stemming from an Intergenic Recombination of the NSP2 and NSP5 Genes Is Defective and Interfering
Authors: Cao Dianjun , Barro Mario , Hoshino Yasutaka
Published: April 2008

Serial undiluted passage of a porcine rotavirus in MA104 cells yielded three distinct virus populations, each of which bore different rearranged genes. Sequencing revealed that each of two populations bore a distinct intragenic recombinant NSP3 gene consisting of a partial duplication in a head-to-tail orientation without altering the NSP3 open reading frame and the third population carried both an intragenic recombinant NSP3 gene and an intergenic recombinant gene (1,647 nucleotides in length) which contained a truncated NSP2 gene inserted into the NSP5 gene at residue 332. The former two populations were viable, whereas the latter population was defective and interfering.
Antibody Is Critical for the Clearance of Murine Norovirus Infection
Authors: Chachu Karen A. , Strong David W. , LoBue Anna D. , Wobus Christiane E. , Baric Ralph S. , Virgin Herbert W.
Published: April 2008

Human noroviruses cause more than 90% of epidemic nonbacterial gastroenteritis. However, the role of B cells and antibody in the immune response to noroviruses is unclear. Previous studies have demonstrated that human norovirus specific antibody levels increase upon infection, but they may not be protective against infection. In this report, we used murine norovirus (MNV), an enteric norovirus, as a model to determine the importance of norovirus specific B cells and immune antibody in clearance of norovirus infection. We show here that mice genetically deficient in B cells failed to clear primary MNV infection as effectively as wild-type mice. In addition, adoptively transferred immune splenocytes derived from B-cell-deficient mice or antibody production-deficient mice were unable to efficiently clear persistent MNV infection in RAG1
−/−
mice. Further, adoptive transfer of either polyclonal anti-MNV serum or neutralizing anti-MNV monoclonal antibodies was sufficient to reduce the level of MNV infection both systemically and in the intestine. Together, these data demonstrate that antibody plays an important role in the clearance of MNV and that immunoglobulin G anti-norovirus antibody can play an important role in clearing mucosal infection.
A Single
Banana Streak Virus
Integration Event in the Banana Genome as the Origin of Infectious Endogenous Pararetrovirus
Authors: Gayral Philippe , Noa-Carrazana Juan-Carlos , Lescot Magali , Lheureux Fabrice , Lockhart Benham E. L. , Matsumoto Takashi , Piffanelli Pietro , Iskra-Caruana Marie-Line
Published: April 2008

Sequencing of plant nuclear genomes reveals the widespread presence of integrated viral sequences known as endogenous pararetroviruses (EPRVs). Banana is one of the three plant species known to harbor infectious EPRVs.
Musa balbisiana
carries integrated copies of
Banana streak virus
(BSV), which are infectious by releasing virions in interspecific hybrids. Here, we analyze the organization of the EPRV of BSV Goldfinger (BSGfV) present in the wild diploid
M. balbisiana
cv. Pisang Klutuk Wulung (PKW) revealed by the study of
Musa
bacterial artificial chromosome resources and interspecific genetic cross. cv. PKW contains two similar EPRVs of BSGfV. Genotyping of these integrants and studies of their segregation pattern show an allelic insertion. Despite the fact that integrated BSGfV has undergone extensive rearrangement, both EPRVs contain the full-length viral genome. The high degree of sequence conservation between the integrated and episomal form of the virus indicates a recent integration event; however, only one allele is infectious. Analysis of BSGfV EPRV segregation among an F1 population from an interspecific genetic cross revealed that these EPRV sequences correspond to two alleles originating from a single integration event. We describe here for the first time the full genomic and genetic organization of the two EPRVs of BSGfV present in cv. PKW in response to the challenge facing both scientists and breeders to identify and generate genetic resources free from BSV. We discuss the consequences of this unique host-pathogen interaction in terms of genetic and genomic plant defenses versus strategies of infectious BSGfV EPRVs.
Identification of a Critical Motif for the Human Immunodeficiency Virus Type 1 (HIV-1) gp41 Core Structure: Implications for Designing Novel Anti-HIV Fusion Inhibitors
Authors: He Yuxian , Cheng Jianwei , Li Jingjing , Qi Zhi , Lu Hong , Dong Mingxin , Jiang Shibo , Dai Qiuyun
Published: April 2008

Human immunodeficiency virus type 1 (HIV-1) entry into the host cell involves a cascade of events and currently represents one of most attractive targets in the search for new antiviral drugs. The fusion-active gp41 core structure is a stable six-helix bundle (6-HB) folded by its trimeric N-terminal heptad repeat (NHR) and C-terminal heptad repeat (CHR). Peptides derived from the CHR region of HIV-1 gp41 are potent fusion inhibitors that target the NHR to block viral and cellular membrane fusion in a dominant negative fashion. However, all CHR peptides reported to date are derived primarily from residues 628 to 673 of gp41; little attention has been paid to the upstream sequence of the pocket binding domain (PBD) in the CHR. Here, we have identified a motif (621QIWNNMT627) located at the upstream region of the gp41 CHR, immediately adjacent to the PBD (628WMEWEREI635). Biophysical characterization demonstrated that this motif is critical for the stabilization of the gp41 6-HB core. The peptide CP621-652, containing the621QIWNNMT627motif, was able to interact with T21, a counterpart peptide derived from the NHR, to form a typical 6-HB structure with a high thermostability (thermal unfolding transition [Tm] value of 82°C). In contrast, the 6-HB formed by the peptides N36 and C34, which has been considered to be a core structure of the fusion-active gp41, had aTmof 64°C. Different from T-20 (brand name Fuseon), which is the first and only HIV-1 fusion inhibitor approved for clinical use, CP621-652 could efficiently block 6-HB formation in a dose-dependent manner. Significantly, CP621-652 had potent inhibitory activity against HIV-1-mediated cell-cell fusion and infection, especially against T-20- and C34-resistant virus. Therefore, our works provide important information for understanding the core structure of the fusion-active gp41 and for designing novel anti-HIV peptides.
Henipavirus
V Protein Association with Polo-Like Kinase Reveals Functional Overlap with STAT1 Binding and Interferon Evasion
Authors: Ludlow Louise E. , Lo Michael K. , Rodriguez Jason J. , Rota Paul A. , Horvath Curt M.
Published: April 2008

Emerging viruses in the paramyxovirus genus
Henipavirus
evade host antiviral responses via protein interactions between the viral V and W proteins and cellular STAT1 and STAT2 and the cytosolic RNA sensor MDA5. Polo-like kinase (PLK1) is identified as being an additional cellular partner that can bind to Nipah virus P, V, and W proteins. For both Nipah virus and Hendra virus, contact between the V protein and the PLK1 polo box domain is required for V protein phosphorylation. Results indicate that PLK1 is engaged by Nipah virus V protein amino acids 100 to 160, previously identified as being the STAT1 binding domain responsible for host interferon (IFN) signaling evasion, via a Thr-Ser-Ser-Pro motif surrounding residue 130. A distinct Ser-Thr-Pro motif surrounding residue 199 mediates the PLK1 interaction with Hendra virus V protein. Select mutations in the motif surrounding residue 130 also influenced STAT1 binding and innate immune interference, and data indicate that the V:PLK1 and V:STAT complexes are V mediated yet independent of one another. The effects of STAT1/PLK1 binding motif mutations on the function the Nipah virus P protein in directing RNA synthesis were tested. Remarkably, mutations that selectively disrupt the STAT or PLK1 interaction site have no effects on Nipah virus P protein-mediated viral RNA synthesis. Therefore, mutations targeting V protein-mediated IFN evasion will not alter the RNA synthetic capacity of the virus, supporting an attenuation strategy based on disrupting host protein interactions.
Rotavirus Infection Accelerates Type 1 Diabetes in Mice with Established Insulitis
Authors: Graham Kate L. , Sanders Natalie , Tan Yan , Allison Janette , Kay Thomas W. H. , Coulson Barbara S.
Published: April 2008

Infection modulates type 1 diabetes, a common autoimmune disease characterized by the destruction of insulin-producing islet β cells in the pancreas. Childhood rotavirus infections have been associated with exacerbations in islet autoimmunity. Nonobese diabetic (NOD) mice develop lymphocytic islet infiltration (insulitis) and then clinical diabetes, whereas NOD8.3 TCR mice, transgenic for a T-cell receptor (TCR) specific for an important islet autoantigen, show more rapid diabetes onset. Oral infection of infant NOD mice with the monkey rotavirus strain RRV delays diabetes development. Here, the effect of RRV infection on diabetes development once insulitis is established was determined. NOD and NOD8.3 TCR mice were inoculated with RRV aged ≥12 and 5 weeks, respectively. Diabetes onset was significantly accelerated in both models (P< 0.024), although RRV infection was asymptomatic and confined to the intestine. The degree of diabetes acceleration was related to the serum antibody titer to RRV. RRV-infected NOD mice showed a possible trend toward increased insulitis development. Infected males showed increased CD8+T-cell proportions in islets. Levels of β-cell major histocompatibility complex class I expression and islet tumor necrosis factor alpha mRNA were elevated in at least one model. NOD mouse exposure to mouse rotavirus in a natural experiment also accelerated diabetes. Thus, rotavirus infection after β-cell autoimmunity is established affects insulitis and exacerbates diabetes. A possible mechanism involves increased exposure of β cells to immune recognition and activation of autoreactive T cells by proinflammatory cytokines. The timing of infection relative to mouse age and degree of insulitis determines whether diabetes onset is delayed, unaltered, or accelerated.