bluuebunny/crossref_metadata_2025 huggingface dataset:
Free-energy conservation in local gyrofluid models
Authors: Scott Bruce D.
Published: October 2005

The details of fluctuation free-energy conservation in gyrofluid models are examined. The polarization equation relates E×B flow and eddy energy to combinations of the potential and the density and perpendicular temperature. These determine the combinations which must appear under derivatives in the moment equations so that not only thermal free energy but also its combination with the E×B energy is properly conserved by the parallel and perpendicular compressional effects. The resulting system exhibits the same qualitative energy-transfer properties as corresponding Braginskii or Landau fluid models. One clear result is that the numerical model built on these equations is well behaved for arbitrarily large perpendicular wave number, allowing exploration of two scale phenomena linking dynamics at the ion and electron gyroradii. When the numerical formulation is done in the globally consistent flux tube model, the results with adiabatic electrons are consistent with the “Cyclone base case” results of gyrokinetic models.
Low-temperature supersonic boundary layer control using repetitively pulsed magnetohydrodynamic forcing
Authors: Nishihara Munetake , Jiang Naibo , Rich J. William , Lempert Walter R. , Adamovich Igor V. , Gogineni Sivaram
Published: October 2005

The paper presents results of magnetohydrodynamic (MHD) supersonic boundary layer control experiments using repetitively pulsed, short-pulse duration, high-voltage discharges in M=3 flows of nitrogen and air in the presence of a magnetic field of B=1.5T. We also have conducted boundary layer flow visualization experiments using laser sheet scattering. Flow visualization results show that as the Reynolds number increases, the boundary layer flow becomes much more chaotic, with the spatial scale of temperature fluctuations decreasing. Combined with density fluctuation spectra measurements using laser differential interferometry (LDI) diagnostics, this behavior suggests that boundary layer transition occurs at stagnation pressures of P0∼200–250Torr. A crossed discharge (pulser+dc sustainer) in M=3 flows of air and nitrogen produced a stable, diffuse, and uniform plasma, with the time-average dc current up to 1.0A in nitrogen and up to 0.8A in air. The electrical conductivity and the Hall parameter in these flows are inferred from the current voltage characteristics of the sustainer discharge. LDI measurements detected the MHD effect on the ionized boundary layer density fluctuations at these conditions. Retarding Lorentz force applied to M=3 nitrogen, air, and N2–He flows produces an increase of the density fluctuation intensity by up to 2dB (about 25%), compared to the accelerating force of the same magnitude. The effect is demonstrated for two possible combinations of the magnetic field and current directions producing the same Lorentz force direction (both for accelerating and retarding force).
Comparison of microinstability properties for stellarator magnetic geometries
Authors: Rewoldt G. , Ku L.-P. , Tang W. M.
Published: October 2005

The microinstability properties of nine distinct magnetic geometries corresponding to different operating and planned stellarators with differing symmetry properties are compared. Specifically, the kinetic stability properties (linear growth rates and real frequencies) of toroidal microinstabilities (driven by ion temperature gradients and trapped-electron dynamics) are compared, as parameters are varied. The familiar ballooning representation is used to enable efficient treatment of the spatial variations along the equilibrium magnetic field lines. These studies provide useful insights for understanding the differences in the relative strengths of the instabilities caused by the differing localizations of good and bad magnetic curvature and of the presence of trapped particles. The associated differences in growth rates due to magnetic geometry are large for small values of the temperature gradient parameter η≡dlnT∕dlnn, whereas for large values of η, the mode is strongly unstable for all of the different magnetic geometries.
Low-frequency electromagnetic fluctuations in thermal-equilibrium, multi-ion-species plasmas
Authors: Toida Mieko , Yoshiya Takashi , Ohsawa Yukiharu
Published: October 2005

Low-frequency electromagnetic thermal fluctuations propagating perpendicular to a magnetic field are theoretically studied with attention to the effect of multiple ion species. In the frequency regime lower than the lower hybrid frequency, there exist three types of modes; magnetosonic mode with ω≃kvA, ion cyclotron modes with ω≃nΩi, and heavy-ion cutoff modes with frequencies slightly higher than the ion-ion hybrid resonance frequencies. The power spectra of magnetic fluctuations due to these modes are obtained analytically and numerically. In a single-ion-species plasma, the magnetosonic mode is an overwhelmingly dominant mode. The autocorrelation function Ck(τ) is thus given by a cosine function with a constant amplitude. In a multi-ion-species plasma, however, the amplitudes of the heavy-ion cutoff modes can be comparable to that of the magnetosonic mode. Therefore, Ck(τ) is initially damped, and its recurrence time is extremely long.
Dynamics and stability of a thin liquid film on a heated rotating disk film with variable viscosity
Authors: Usha R. , Ravindran R. , Uma B.
Published: October 2005

A theoretical analysis of the thermal effects on the dynamics of a thin nonuniform film of a nonvolatile incompressible viscous fluid on a heated rotating disk has been considered and the effects of temperature-dependent viscosity and surface tension have been analyzed. A nonlinear evolution equation describing the shape of the film interface has been derived as a function of space and time and its stability characteristics have been examined using linear theory. It has been observed that the infinitesimal disturbances decay for small wave numbers and are transiently stable for large wave numbers, for both zero and nonzero values of Biot number.
Numerical upper bounds on convective heat transport in a layer of fluid of finite Prandtl number: Confirmation of Howard’s analytical asymptotic single-wave-number bound
Authors: Vitanov Nikolay K.
Published: October 2005

By means of the Howard-Busse method of the optimum theory of turbulence we investigate numerically the upper bounds on the Nusselt number in a heated-from-below horizontal layer of fluid of finite Prandtl number for the case of rigid boundaries. The bounds are obtained by the solutions of the Euler-Lagrange equations of a variational problem possessing up to three wave numbers. The obtained results are compared to the numerical results for the case of fluid layer with stress-free boundaries [N. K. Vitanov and F. H. Busse, “Upper bounds on heat transport in a horizontal fluid layer with stress-free boundaries,” ZAMP 48, 310 (1997)] as well as to the numerical and analytical asymptotic results obtained by Howard [“Heat transport by turbulent convection,” J. Fluid Mech. 17, 405 (1963)], Busse [“On Howard’s upper bound for heat transport by turbulent convection,” J. Fluid Mech. 37, 457 (1969)], and Strauss [“On the upper bounding approach to thermal convection at moderate Rayleigh numbers, II. Rigid boundaries,” Dyn. Atm. Oceans 1, 77 (1976)]. We show that for low and intermediate Rayleigh numbers the numerical bounds are positioned below the analytical asymptotic bounds obtained by Howard and Busse. For large Rayleigh numbers the numerical bounds tend to approach the analytical asymptotic bounds. We confirm numerically the bound obtained by Howard for the case of one-wave-number solution of the Euler-Lagrange equations. As the region of validity of the results of the analytical asymptotic theory for solutions of the Euler-Lagrange equations with two and three wave numbers lies in the area of very high Rayleigh numbers the values of the second and third wave numbers are different from their analytical asymptotic values for the values of the Rayleigh number reached by the numerical computation.
Poloidal flow damping with potato orbits in tokamaks
Authors: Shaing K. C.
Published: October 2005

The poloidal flow damping rate in the vicinity of the magnetic axis in tokamaks is calculated using the time-dependent plasma viscosity. It is found that the damping rate is of the order of νii∕ft2, where νii is the ion-ion collision frequency, and ft is the fraction of the trapped potatoes. The corresponding neoclassical polarization or inertia enhancement factor is [1+(σpq2∕ft)], where σp is a numerical number of the order of unity, and q is the safety factor.
Unidirectional flow of a thin rivulet on a vertical substrate subject to a prescribed uniform shear stress at its free surface
Authors: Wilson S. K. , Duffy B. R.
Published: October 2005

We use the lubrication approximation to analyze the steady unidirectional flow of a thin rivulet on a vertical substrate subject to a prescribed uniform longitudinal shear stress at its free surface. In particular, we determine the quasisteady stability of a rivulet of prescribed flux, and calculate when it is energetically favorable for a rivulet to split into two narrower rivulets.
Decomposition in as-grown (Ga,In)(N,As) quantum wells
Authors: Kong X. , Trampert A. , Tournié E. , Ploog K. H.
Published: October 2005

We report on the investigation of the local element distribution in as-grown (Ga,In)(N,As) quantum wells with high In and N contents by using low-loss electron energy-loss spectroscopy combined with dark-field transmission electron microscopy. The (Ga,In)(N,As) quantum wells were grown on GaAs(001) substrates at different growth temperatures by molecular-beam epitaxy. Lateral modulations on the nanometer scale were detected with reversal In and N distributions pointing to the existence of regions with a more favorable Ga–N and In–As bond configurations, respectively. These composition fluctuations are the driving force for the morphological instabilities at the interfaces. Lowering the growth temperature of the quantum well results in a more homogeneous element distribution of the quaternary compound. This result is discussed with regard to the influence of the epitaxial strain and cohesive bond energy on the alloy formation during epitaxial growth.
Exciton hopping and nonradiative decay in AlGaN epilayers
Authors: Kazlauskas K. , Žukauskas A. , Tamulaitis G. , Mickevičius J. , Shur M. S. , Fareed R. S. Qhalid , Zhang J. P. , Gaska R.
Published: October 2005

Monte Carlo simulation of phonon-assisted localized exciton hopping has been employed to describe the photoluminescence linewidth variation with temperature and to reveal band potential profile of ternary AlGaN epilayers with different carrier lifetimes. The lifetimes of 30 and 190 ps were experimentally determined in the layers with AlN buffers grown by conventional metal-organic chemical vapor deposition (MOCVD) and by migration-enhanced MOCVD (MEMOCVD™), respectively. The potential profile in AlGaN is shown to consist of double-scaled fluctuations. Exciton hopping in Al0.26Ga0.74N occurs within the random potential fluctuations (on the scale σ≈19meV) in isolated low-potential regions with the average localization energy dispersed on the scale Γ≈19meV. Such a pattern of band potential profile was found to be independent on the growth technique used for the deposition of their AlN buffer layers. This implies that the large difference in carrier lifetimes estimated in the AlGaN epilayers with the same Al content is caused by different densities of nonradiative recombination centers rather than by carrier localization in the potential fluctuations.
Dielectric mismatch effects on the electronic and optical properties of GaN∕HfO2 quantum wells
Authors: Pereira T. A. S. , de Sousa J. S. , Farias G. A. , Freire J. A. K. , Degani M. H. , Freire V. N.
Published: October 2005

In this work, we demonstrate that the image charges effect induced by the dielectric mismatch strongly modifies the electronic structure of GaN∕HfO2 quantum wells (QWs) in such a way that the ideal QW confinement model is no longer suitable for the description of these systems. Particularly, two different confinement regimes were observed for narrow and wide QWs. In the former, electrons, light and heavy holes are spatially localized in the same region. In wide QWs, heavy holes are confined in the interfacial regions due to the strong attraction of the image charges, which does not occur for electrons and light holes. As a consequence, optical transitions involving electrons and heavy holes become less efficient in wide QWs.
Ultraslow light (<200m∕s) propagation in a semiconductor nanostructure
Authors: Palinginis Phedon , Crankshaw Shanna , Sedgwick Forrest , Kim Eui-Tae , Moewe Michael , Chang-Hasnain Connie J. , Wang Hailin , Chuang Shun-Lien
Published: October 2005

We report time-domain measurements of ultraslow light propagation in a semiconductor quantum-well structure using coherent population oscillation. Delays greater than 1 ns are achieved for an amplitude-modulated optical beam propagating through a 195-nm-long active region, corresponding to group velocities less than 200m∕s. Delays can be easily varied by adjusting the intensity of the control laser. The bandwidth is suitable to delay sub-GHz modulated optical signals.
Patterning of sub-10-nm Ge islands on Si(100) by directed self-assembly
Authors: Guise Olivier , Yates John T. , Levy Jeremy , Ahner Joachim , Vaithyanathan Venugopalan , Schlom Darrell G.
Published: October 2005

A process is reported for creating arbitrary patterns of sub-10-nm Ge islands on a Si(100) substrate by directed self-assembly. Carbon-based templates are created on Si substrates by electron-beam-induced deposition using high-resolution electron beam lithography. Ozone etching, followed by annealing in ultra-high vacuum, yields small (<4nm) SiC nucleation sites for subsequently deposited Ge. Quantitative analysis of atomic force microscope images reveals templated Ge islands with mean diameter d∼8nm, averaging 2000±500 atoms per island, with controlled spacings as small as 35 nm, and 2 nm absolute positional accuracy. The Ge∕Si nanostructures reported here may find use in end-of-scaling classical computing and single-electron devices and spin-based quantum computing architectures.
Thermally induced second-order nonlinearity in silica-based glasses
Authors: Fokine Michael , Saito Kazuya , Ikushima Akira J.
Published: October 2005

This letter presents the observation of second-harmonic generation in pure silica and germanium-doped glass samples after heat treatment at elevated temperatures followed by rapid quenching to room temperature. No applied voltage has been used and the samples do not contain crystals. The induced nonlinearity is located near the surfaces of the sample. The possible origin of the second-order nonlinearity is discussed.
A paracrine peptide sex pheromone also acts as an autocrine signal to induce plasmid transfer and virulence factor expressionin vivo
Authors: Chandler Josephine R. , Hirt Helmut , Dunny Gary M.
Published: October 2005

The peptide pheromone cCF10 ofEnterococcus faecalisis an intercellular signal for induction of conjugative transfer of plasmid pCF10 from donor cells to recipient cells. When a donor cell is exposed to recipient-produced cCF10, expression of the pCF10-encoded aggregation substance of pCF10 (Asc10) and other conjugation gene products is activated. Asc10 also increases enterococcal virulence in several models, and when donor cells are grown in animals or in plasma, Asc10 expression is induced by means of the cCF10-sensing machinery. Plasmid pCF10 carries two genes that function to prevent self-induction by endogenous cCF10 in donor cells. The membrane protein PrgY reduces endogenous pheromone activity in donor cells, and the inhibitor peptide iCF10 neutralizes the residual endogenous cCF10 that escapes PrgY. In the current study, we found thatE. faecalisstrains with allelic replacements abolishing active cCF10 production showed reduced ability to acquire pCF10 by conjugation;prgY-null mutations had no phenotype in the cCF10-negative strains. We observed that expression of the mRNA for iCF10 was reduced in this background and that these mutations also blocked plasma induction of Asc10 expression. These findings support a model in which plasma induction in wild-type donors results from iCF10 inactivation by a plasma component, causing disruption of a precisely maintained balance of iCF10 to cCF10 activity and allowing subsequent induction by endogenous cCF10. Although cCF10 has traditionally been viewed as an intercellular signal, these results show that pCF10 has also adapted cCF10 as an autocrine signal that activates expression of virulence and conjugation functions.
Friend spleen focus-forming virus transforms rodent fibroblasts in cooperation with a short form of the receptor tyrosine kinase Stk
Authors: Nishigaki Kazuo , Hanson Charlotte , Jelacic Tanya , Thompson Delores , Ruscetti Sandra
Published: October 2005

Friend spleen focus-forming virus (SFFV) causes rapid erythroleukemia in mice due to expression of its unique envelope glycoprotein, gp55. Erythroid cells expressing SFFV gp55 proliferate in the absence of their normal regulator erythropoietin (Epo) because of constitutive activation of Epo signal transduction pathways. Although SFFV infects many cell types, deregulation of cell growth occurs only when SFFV infects erythroid cells, suggesting that these cells express unique proteins that the virus requires to mediate its biological effects. Not only do erythroid cells express the Epo receptor (EpoR), but those from mice susceptible to SFFV-induced erythroleukemia also express a short form of the receptor tyrosine kinase Stk (sf-Stk). In erythroid cells, SFFV gp55 interacts with the EpoR complex and sf-Stk, leading to activation of the kinase and constitutive activation of signal transducing molecules. In this study, we demonstrate that SFFV gp55 can also deregulate the growth of nonerythroid cells when it is coexpressed with sf-Stk. Expression of SFFV gp55 in rodent fibroblasts engineered to express sf-Stk induced their transformation, as demonstrated by focus formation and anchorage-independent growth
in vitro
. This transformation by SFFV gp55 requires the kinase activity of sf-Stk and the presence of its extracellular domain but not expression of the EpoR or the tyrosine kinase Jak2, which is required for activation of signal transduction pathways through the EpoR. Thus, expression of SFFV gp55 in nonerythroid cells coexpressing sf-Stk results in their uncontrolled growth, demonstrating a previously unrecognized mechanism for retrovirus transformation of rodent fibroblasts and providing insight into SFFV-induced disease.
Structure and properties of α-synuclein and other amyloids determined at the amino acid level
Authors: Del Mar Charyl , Greenbaum Eric A. , Mayne Leland , Englander S. Walter , Woods Virgil L.
Published: October 2005

The structure of α-synuclein (α-syn) amyloid was studied by hydrogen-deuterium exchange by using a fragment separation–MS analysis. The conditions used made it possible to distinguish the exchange of unprotected and protected amide hydrogens and to define the order/disorder boundaries at close to amino acid resolution. The soluble α-syn monomer exchanges its amide hydrogens with water hydrogens at random coil rates, consistent with its natively unstructured condition. In assembled amyloid, long N-terminal and C-terminal segments remain unprotected (residues 1–≈38 and 102–140), although the N-terminal segment shows some heterogeneity. A continuous middle segment (residues ≈39–101) is strongly protected by systematically H-bonded cross-β structure. This segment is much too long to fit the amyloid ribbon width, but non-H-bonded amides expected for direction-changing loops are not apparent. These results and other known constraints specify that α-syn amyloid adopts a chain fold like that suggested before for amyloid-β [Petkova
et al.
(2002)
Proc. Natl. Acad Sci. USA
99, 16742–16747] but with a short, H-bonded interlamina turn. More generally, we suggest that the prevalence of accidental amyloid formation derives mainly from the exceptional ability of the main chain in a structurally relaxed β-conformation to adapt to and energy-minimize side-chain mismatching. Seeding specificity, strain variability, and species barriers then arise because newly added parallel in-register chains must faithfully reproduce the same set of adaptations.
Comparative gene expression analysis of blood and brain provides concurrent validation of
SELENBP1
up-regulation in schizophrenia
Authors: Glatt Stephen J. , Everall Ian P. , Kremen William S. , Corbeil Jacques , Šášik Roman , Khanlou Negar , Han Mark , Liew Choong-Chin , Tsuang Ming T.
Published: October 2005

Microarray techniques hold great promise for identifying risk factors for schizophrenia (SZ) but have not yet generated widely reproducible results due to methodological differences between studies and the high risk of type I inferential errors. Here we established a protocol for conservative analysis and interpretation of gene expression data from the dorsolateral prefrontal cortex of SZ patients using statistical and bioinformatic methods that limit false positives. We also compared brain gene expression profiles with those from peripheral blood cells of a separate sample of SZ patients to identify disease-associated genes that generalize across tissues and populations and further substantiate the use of gene expression profiling of blood for detecting valid SZ biomarkers. Implementing this systematic approach, we: (
i
) discovered 177 putative SZ risk genes in brain, 28 of which map to linked chromosomal loci; (
ii
) delineated six biological processes and 12 molecular functions that may be particularly disrupted in the illness; (
iii
) identified 123 putative SZ biomarkers in blood, 6 of which (
BTG1
,
GSK3A
,
HLA-DRB1
,
HNRPA3
,
SELENBP1
, and
SFRS1
) had corresponding differential expression in brain; (
iv
) verified the differential expression of the strongest candidate SZ biomarker (
SELENBP1
) in blood; and (
v
) demonstrated neuronal and glial expression of
SELENBP1
protein in brain. The continued application of this approach in other brain regions and populations should facilitate the discovery of highly reliable and reproducible candidate risk genes and biomarkers for SZ. The identification of valid peripheral biomarkers for SZ may ultimately facilitate early identification, intervention, and prevention efforts as well.
Group A
Streptococcus
produce pilus-like structures containing protective antigens and Lancefield T antigens
Authors: Mora Marirosa , Bensi Giuliano , Capo Sabrina , Falugi Fabiana , Zingaretti Chiara , Manetti Andrea G. O. , Maggi Tiziana , Taddei Anna Rita , Grandi Guido , Telford John L.
Published: October 2005

Although pili have long been recognized in Gram-negative pathogens as important virulence factors involved in adhesion and invasion, very little is known about extended surface organelles in Gram-positive pathogens. Here we report that Group A
Streptococcus
(GAS), a Gram-positive human-specific pathogen that causes pharyngitis, impetigo, invasive disease, necrotizing fasciitis, and autoimmune sequelae has long, surface-exposed, pilus-like structures composed of members of a family of extracellular matrix-binding proteins. We describe four variant pili and show that each is recognized by a specific serum of the Lancefield T-typing system, which has been used for over five decades to characterize GAS isolates. Furthermore, we show that immunization of mice with a combination of recombinant pilus proteins confers protection against mucosal challenge with virulent GAS bacteria. The data indicate that induction of a protective immune response against these structures may be a useful strategy for development of a vaccine against disease caused by GAS infection.
Suffix-tree analyser (STAN): looking for nucleotidic and peptidic patterns in chromosomes
Authors: Nicolas Jacques , Durand Patrick , Ranchy Grégory , Tempel Sébastien , Valin Anne-Sophie
Published: October 2005

Summary: We have developed STAN (suffix-tree analyser), a tool to search for nucleotidic and peptidic patterns within whole chromosomes. Pattern syntax uses a string variable grammar-like formalism which allows the description of complex patterns including ambiguities, insertions/deletions, gaps, repeats and palindromes. STAN is based on a reduction to multipart matching on a suffix-tree data structure and can handle large DNA sequences, whether assembled or not.

Availability: STAN is accessible online at

Contact: stan@irisa.fr
Athena: a resource for rapid visualization and systematic analysis of Arabidopsis promoter sequences
Authors: O'Connor Timothy R. , Dyreson Curtis , Wyrick John J.
Published: October 2005

Summary: To better understand the regulatory networks that control plant gene expression, tools are needed to systematically analyze and visualize promoter regulatory sequences in Arabidopsis thaliana. We have developed the Athena database, which contains 30 067 predicted Arabidopsis promoter sequences and consensus sequences for 105 previously characterized transcription factor (TF) binding sites. Athena provides four novel tools to facilitate the analysis of promoter sequences: a promoter visualization tool to enable the rapid inspection of key regulatory sequences in multiple promoters; a TF binding site enrichment tool to identify statistically over-represented TF sites occurring in a user-selected subset of promoters; a data-mining tool to rapidly select promoter sequences containing the specified combination of TF binding sites; and a tool to display the distribution of TF binding site positions in a selected set of promoter sequences.

Availability:  

Contact:  jwyrick@wsu.edu
Evolution of a rare vaccine-derived multirecombinant poliovirus
Authors: Karakasiliotis Ioannis , Paximadi Eleni , Markoulatos Panayotis
Published: October 2005

Recombination is one of the mechanisms by which viral genomes evolve. A vaccine-derived multirecombinant poliovirus strain was isolated from a 5-month-old child with vaccine-associated paralytic poliomyelitis after oral poliovirus vaccine administration. The isolate had an S2/S1/S2/S1 primary genomic structure as revealed by restriction fragment length polymorphism and sequencing analysis. Recombination of the middle S1/S2 region is extremely rare and one of the few characterized types of recombination with Sabin type 1 as a 5′ partner. An attempt was made to perform evolutionary analysis of the contributing sequences using the identified mutations in comparison with the original Sabin sequences. A hypothesis is proposed for the order in which the identified recombination events occurred.
Hantavirus Gc glycoprotein: evidence for a class II fusion protein
Authors: Tischler Nicole D. , Gonzalez Angel , Perez-Acle Tomas , Rosemblatt Mario , Valenzuela Pablo D. T.
Published: October 2005

Hantavirus cell entry is promoted by its envelope glycoproteins, Gn and Gc, through cell attachment and by fusion between viral and endosomal membranes at low pH. However, the role of Gn and Gc in receptor binding and cell fusion has not yet been defined. In this work, a sequence presenting characteristics similar to those of class II fusion peptides (FPs) of alphavirus E1 and flavivirus E proteins is identified within the hantavirus Gc glycoprotein. A three-dimensional comparative molecular model based on crystallographic data of tick-borne encephalitis virus E protein is proposed for the Andes virus (ANDV) Gc ectodomain, which supports a feasible class II fusion-protein fold. In vitro experimental evidence is provided for the binding activity of the ANDV FP candidate to artificial membranes, as demonstrated by fluorescence anisotropy assays. Taken together, these results support the hypothesis that the Gc glycoprotein of hantaviruses and of other members of the family Bunyaviridae directs the viral fusion activity and that it may be classified as a class II viral fusion protein.
Alpha interferon inhibits translation mediated by the internal ribosome entry site of six different hepatitis C virus genotypes
Authors: Hazari Sidhartha , Patil Asha , Joshi Virendra , Sullivan Deborah E. , Fermin Cesar D. , Garry Robert F. , Elliott Richard M. , Dash Srikanta
Published: October 2005

Certain genotypes ofhepatitis C virus(HCV) respond less often than others to treatment with interferon (IFN). The mechanisms for this differential response are not known. In this report antiviral effects of IFN-α2b on translation were examined in a hepatic cell line using chimeric clones of internal ribosome entry site (IRES) sequences from six different HCV genotypes and the green fluorescence protein (GFP) gene. As a control, IFN action at the level of the IRES was examined in the presence of different cytokines. It was determined that IFN-α2b specifically inhibited the translation of GFP mediated by IRES sequences from six major HCV genotypes in a concentration-dependent manner. Other cytokines including tumour necrosis factor alpha, transforming growth factor beta 1, interleukin 1 and interleukin 6 have no inhibitory effect. The inhibition of translation in these experiments was not due to extensive intracellular degradation of IRES-GFP mRNA. These results suggest that the antiviral action of IFN-α2b blocks IRES-mediated translation and this effect is the same among HCVs of other genotypes.
A genetic-algorithm approach to simulating human immunodeficiency virus evolution reveals the strong impact of multiply infected cells and recombination
Authors: Bocharov Gennady , Ford Neville J. , Edwards John , Breinig Tanja , Wain-Hobson Simon , Meyerhans Andreas
Published: October 2005

It has been previously shown that the majority of human immunodeficiency virus type 1 (HIV-1)-infected splenocytes can harbour multiple, divergent proviruses with a copy number ranging from one to eight. This implies that, besides point mutations, recombination should be considered as an important mechanism in the evolution of HIV within an infected host. To explore in detail the possible contributions of multi-infection and recombination to HIV evolution, the effects of major microscopic parameters of HIV replication (i.e. the point-mutation rate, the crossover number, the recombination rate and the provirus copy number) on macroscopic characteristics (such as the Hamming distance and the abundance of n-point mutants) have been simulated in silico. Simulations predict that multiple provirus copies per infected cell and recombination act in synergy to speed up the development of sequence diversity. Point mutations can be fixed for some time without fitness selection. The time needed for the selection of multiple mutations with increased fitness is highly variable, supporting the view that stochastic processes may contribute substantially to the kinetics of HIV variation in vivo.
Epstein–Barr virus-induced B-cell transformation: quantitating events from virus binding to cell outgrowth
Authors: Shannon-Lowe Claire , Baldwin Gouri , Feederle Regina , Bell Andrew , Rickinson Alan , Delecluse Henri-Jacques
Published: October 2005

Epstein–Barr virus (EBV) infection and growth activation of human B cells is central to virus biology and disease pathogenesis, but is poorly understood in quantitative terms. Here, using virus at defined m.o.i., the different stages of this process at the single-cell level are followedin vitro. Virus binding to the B-cell surface, assayed by quantitative PCR, is highly efficient, particularly at the low m.o.i. values that most likely reflect physiologic eventsin vivo. However, only 10–15 % of bound virus genomes reach the cell nucleus, as visualized by sensitive fluorescencein situhybridization (FISH) assay; viral genomes acquired per cell nucleus range from 1 to >10, depending on the m.o.i. Thereafter, despite differences in initial genome load, almost all nuclear genome-positive cells then go on to express the virus-encoded nuclear antigen EBNA2, upregulate the cell activation antigen CD23 and transit the cell cycle. EBNA2-positive cells in the first cycle post-infection then grow out to lymphoblastoid cell lines (LCLs) just as efficiently as do cells limiting-diluted from already established LCLs. This study therefore identifies EBV genome delivery to the nucleus as a key rate-limiting step in B-cell transformation, and highlights the remarkable efficiency with which a single virus genome, having reached the nucleus, then drives the transformation programme.
Antiviral activity of morpholino oligomers designed to block various aspects of Equine arteritis virus amplification in cell culture
Authors: van den Born Erwin , Stein David A. , Iversen Patrick L. , Snijder Eric J.
Published: October 2005

The antiviral efficacy of ten antisense phosphorodiamidate morpholino oligomers (PMOs) directed against Equine arteritis virus (EAV), a nidovirus belonging to the family Arteriviridae, was evaluated in mammalian (Vero-E6) cells. Peptide-conjugated PMOs (P-PMOs) supplied in cell culture medium at micromolar concentrations were efficiently taken up by Vero-E6 cells and were minimally cytotoxic. The P-PMOs were designed to base pair to RNA sequences involved in different aspects of EAV amplification: genome replication, subgenomic mRNA synthesis, and translation of genome and subgenomic mRNAs. A novel recombinant EAV, expressing green fluorescent protein as part of its replicase polyproteins, was used to facilitate drug screening. A moderate reduction of EAV amplification was observed with relatively high concentrations of P-PMOs designed to anneal to the 3′-terminal regions of the viral genome or antigenome. To determine if the synthesis of subgenomic mRNAs could be specifically reduced, transcription-regulating sequences essential for their production, but not for the production of genomic RNA, were targeted, but these P-PMOs were found to be ineffective at transcription interference. In contrast, all four P-PMOs designed to base pair with targets in the genomic 5′ untranslated region markedly reduced virus amplification in a sequence-specific and dose-responsive manner. At concentrations in the low micromolar range, some of the P-PMOs tested completely inhibited virus amplification. In vitro translation assays showed that these P-PMOs were potent inhibitors of translation. The data suggest that these compounds could be useful as reagents for exploring the molecular mechanics of nidovirus translation and have anti-EAV potential at relatively low concentrations.
Cysteine residues of the porcine reproductive and respiratory syndrome virus small envelope protein are non-essential for virus infectivity
Authors: Lee Changhee , Yoo Dongwan
Published: October 2005

Porcine reproductive and respiratory syndrome virus (PRRSV) open reading frame (ORF) 2a contains a small internal ORF (2b) capable of encoding a protein of 73 aa, termed E protein. The function of E protein is currently unknown. The E protein possesses two cysteines at positions 49 and 54 that are highly conserved among North American isolates. In the present study, it was shown that E protein did not homodimerize with itself nor did it heterodimerize with the nucleocapsid (N) protein. However, E protein was interactive non-covalently with itself or with the N protein as shown by pull-down assays. The significance of the E protein cysteine residues on virus replication was determined using an infectious clone. Each cysteine was substituted by serine and the mutations were introduced into a full-length clone of PRRSV. When transfected into Marc-145 cells, all cysteine mutant clones induced PRRSV-specific cytopathic effects and produced infectious progeny virus. The data indicate that cysteine residues in the E protein are not essential for replication of North American genotype PRRSV.
High genetic variability and evidence for plant-to-plant transfer of Banana mild mosaic virus
Authors: Teycheney Pierre-Yves , Laboureau Nathalie , Iskra-Caruana Marie-Line , Candresse Thierry
Published: October 2005

A total of 154 partial nucleotide sequences within theBanana mild mosaic virus(BanMMV) ORF1, which encodes the viral RNA-dependent RNA polymerase (RdRp), was obtained from 68 distinct infected banana accessions originating from various locations worldwide. The 310 nt sequences displayed a high level of variability with a mean pairwise nucleotide sequence divergence level of 20·4 %. This situation resulted essentially from a high rate of synonymous mutations. A similar analysis was performed for a limited selection of 10 banana accessions (30 sequences) on the region comprising approximately the last 310 nt of the BanMMV genome. This region corresponds to the 3′ end of ORF5, which encodes the coat protein (234 nt), and to the 3′ non-coding region. This analysis confirmed the high level of diversity observed in the RdRp dataset, characterized by a high level of synonymous mutations. Analysis of intra-host diversity indicated the existence of two distinct situations, with some plants containing only closely related sequence variants, whereas others contained widely divergent isolates. Analyses indicated that BanMMV genetic diversity is not structured by the geographical origin of the infectedMusaaccessions or by their genotype. This situation may be, in part, explained by the exchange of banana germplasm between different parts of the world and also by plant-to-plant transfer of virus isolates, the evidence for which is, for the first time, provided by this study.
Antigenic and genetic characterization of rabies viruses isolated from domestic and wild animals of Brazil identifies the hoary fox as a rabies reservoir
Authors: Bernardi F. , Nadin-Davis S. A. , Wandeler A. I. , Armstrong J. , Gomes A. A. B. , Lima F. S. , Nogueira F. R. B. , Ito F. H.
Published: October 2005

Fifty Brazilian rabies viruses, collected from many different animal species and several regions of the country, were characterized by partial sequencing of the central, variable region of the P gene, a locus useful for sensitive molecular epidemiological studies. Phylogenetic analysis of the sequences, which included comparison with other rabies strains recovered from throughout the Americas, identified three main groups of Brazilian viruses, arbitrarily designated BRL-1 to BRL-3. BRL-1 was found in terrestrial carnivores and clusters with other American strains of the cosmopolitan lineage. BRL-2 comprised two distinct isolates, recovered from two species of non-haematophagous bats, that had evolutionary links to insectivorous-bat-derived strains of North America. BRL-3 consisted of isolates from vampire bats and from livestock species probably infected via contact with vampire bats. The terrestrial group was further subdivided into three subtypes: BRL-1a was associated exclusively with dogs and cats, while BRL-1b and BRL-1c were found exclusively in hoary foxes. These observations strongly support the role of the Brazilian hoary fox as a rabies reservoir. Screening of representative Brazilian rabies viruses against a collection of anti-rabies monoclonal antibodies (mAbs) identified a small panel of mAbs that could be used to discriminate between all Brazilian subgroups as defined by genetic classification in this study.
A novel subgroup of rhadinoviruses in ruminants
Authors: Li Hong , Gailbreath Katherine , Flach Edmund J. , Taus Naomi S. , Cooley Jim , Keller Janice , Russell George C. , Knowles Donald P. , Haig David M. , Oaks J. Lindsay , Traul Donald L. , Crawford Timothy B.
Published: October 2005

In the course of investigating the malignant catarrhal fever (MCF) subgroup of rhadinoviruses, seven novel rhadinoviruses were identified in a variety of ruminants, including domestic sheep, bighorn sheep, bison, black-tailed deer, mule deer, fallow deer, elk and addax. Based on the DNA polymerase gene sequences, these newly recognized viruses clustered into a second distinct subgroup in ruminants with three members identified previously in cattle, goats and oryx. Phylogenetic analysis revealed that the currently known ruminant rhadinoviruses appear to comprise three distinct genetic lineages: (i) the MCF subgroup, defined by sequence identity and the presence of the 15A antigenic epitope; (ii) a second distinct subgroup, devoid of the 15A epitope, which contains the previously reported bovine lymphotropic herpesvirus and related viruses; and (iii) a third distinct subgroup represented by Bovine herpesvirus 4. Comparison of phylogenetic trees between the rhadinoviruses and their corresponding hosts further supports the gammaherpesvirus and host co-evolution theory.
Herpes simplex virus type 1 immediate-early protein ICP0 diffuses out of infected rabbit corneas
Authors: Naito Julie , Mott Kevin R. , Osorio Nelson , Jin Ling , Perng Guey-Chuen
Published: October 2005

Herpes stromal keratitis (HSK) results from infection of herpes simplex virus (HSV) in the cornea. Recurrent HSV infection is a leading cause of corneal scarring and visual loss. Although it is generally thought that HSK is the result of an immune response to one or more viral proteins, no viral proteins have been detected in HSK corneas. Thus, the viral proteins involved in HSK, if any, remain undetermined. In contrast, it is reported here that when HSK corneal buttons from latently infected rabbits were fixed using standard procedures, the important immediate-early HSV-1 protein ICP0 was readily detected in the fixative by Western blotting. Similarly, when HSK corneal buttons were soaked in buffer (rather than fixative), ICP0 was readily detected in the soaking buffer. Other HSV-1 proteins were not detected either in the fixative or in the soaking buffer. It is also reported here that ICP0 was consistently detected in virus-free tears from the eyes of rabbits acutely infected with HSV-1. These results suggest that ICP0 rapidly diffuses out of the cornea and may explain why ICP0 was detected in the fixative of HSK corneas and in the soaking buffer of acutely infected corneas.
Prevalence of antibodies to Vaccinia virus after smallpox vaccination in Italy
Authors: Pütz Mike M. , Alberini Isabella , Midgley Claire M. , Manini Ilaria , Montomoli Emanuele , Smith Geoffrey L.
Published: October 2005

Decades after smallpox was eradicated and vaccination discontinued, the level of residual immunity in today's population is largely unknown. This study describes an epidemiological assessment in Italians of antibodies against the intracellular mature virus (IMV) and extracellular envelope virus (EEV) forms of Vaccinia virus. Serum samples (n=642) were taken in 1993 and 2003 from people between 11 and 102 years old. Most citizens >27 years old were positive for antibodies to IMV and EEV. These antibodies were long-lasting and similar titres were present in citizens between 30 and 100 years old. Serum samples from 1993 and 2003 displayed very similar EEV- and IMV-specific antibody titres. By using these data and demographic considerations, it was predicted that, in 2003, 46 % of the Italian population were positive for both IMV and EEV, 42 % were negative for both and 12 % were positive for one antigen.
Hepatitis C virus infection of primary tupaia hepatocytes leads to selection of quasispecies variants, induction of interferon-stimulated genes and NF-κB nuclear translocation
Authors: Guitart Anunciata , Riezu-Boj José-Ignacio , Elizalde Edurne , Larrea Esther , Berasain Carmen , Aldabe Rafael , Civeira Maria Pilar , Prieto Jesús
Published: October 2005

Systems forin vitroculture ofHepatitis C virus(HCV) are essential tools to analyse virus–cell interactions and to investigate relevant pathophysiological aspects of HCV infection. Although the HCV replicon methodology has increased our understanding of HCV biology, this system does not reproduce the natural infection. Recently, tupaia (Tupaia belangeri chinensis) hepatocytes have been utilized forin vitroculture of HCV. In the present work, primary tupaia hepatocytes infectedin vitrowith HCV were used to analyse the evolution of HCV quasispecies in infected cells and the ability of the virus to influence antiviral and proinflammatory responses in cells sustaining virus replication. The results confirmed the potential of tupaia hepatocytes as a model for HCV infection, although this system is limited by rapid loss of differentiated cell phenotype in culture. These findings revealed an extraordinary plasticity of HCV quasispecies, which underwent rapid evolution to tupaia-tropic variants as early as 24 h after infection. It was also shown that HCV could activate interferon-sensitive genes, albeit modestly in comparison with other viruses such asSemliki Forest virus. Importantly, HCV activated NF-κB in primary hepatocytes and upregulated NF-κB-responsive genes including the chemokines MCP-1 and CXCL2 (MIP-2). This effect may play a role in induction of the hepatic inflammatory reactionin vivo. In summary, HCV quasispecies adapt rapidly to the specific biology of the host and HCV stimulates a blunted interferon response while inducing a proinflammatory phenotype in the infected cell.
Complete coding sequences of the rabbitpox virus genome
Authors: Li G. , Chen N. , Roper R. L. , Feng Z. , Hunter A. , Danila M. , Lefkowitz E. J. , Buller R. M. L. , Upton C.
Published: October 2005

Rabbitpox virus (RPXV) is highly virulent for rabbits and it has long been suspected to be a close relative of vaccinia virus. To explore these questions, the complete coding region of the rabbitpox virus genome was sequenced to permit comparison with sequenced strains of vaccinia virus and other orthopoxviruses. The genome of RPXV strain Utrecht (RPXV-UTR) is 197 731 nucleotides long, excluding the terminal hairpin structures at each end of the genome. The RPXV-UTR genome has 66·5 % A+T content, 184 putative functional genes and 12 fragmented ORF regions that are intact in other orthopoxviruses. The sequence of the RPXV-UTR genome reveals that two RPXV-UTR genes have orthologues in variola virus (VARV; the causative agent of smallpox), but not in vaccinia virus (VACV) strains. These genes are a zinc RING finger protein gene (RPXV-UTR-008) and an ankyrin repeat family protein gene (RPXV-UTR-180). A third gene, encoding a chemokine-binding protein (RPXV-UTR-001/184), is complete in VARV but functional only in some VACV strains. Examination of the evolutionary relationship between RPXV and other orthopoxviruses was carried out using the central 143 kb DNA sequence conserved among all completely sequenced orthopoxviruses and also the protein sequences of 49 gene products present in all completely sequenced chordopoxviruses. The results of these analyses both confirm that RPXV-UTR is most closely related to VACV and suggest that RPXV has not evolved directly from any of the sequenced VACV strains, since RPXV contains a 719 bp region not previously identified in any VACV.
A Review of Eating Disorders and Suicide Risk in Adolescence
Authors: Dancyger Ida F. , Fornari Victor M.
Published: October 2005

This review examines the literature during the past 10 years about suicide risk and suicide during adolescence and young adulthood of individuals with eating disorders. Epidemiological surveys are summarized, including suicide rates, parasuicidal behaviors, associated risk factors, and comorbid psychopathology. Critical implications for the comprehensive assessment and treatment planning, including safety considerations, are discussed. Two clinical cases of women with long-standing eating disorders are described to highlight both the pragmatic considerations and the complex clinical challenges of working with patients with eating disorders who become suicidal. The potentially life-threatening issues of safety have not received sufficient attention, neither in the medical literature nor by the treating clinicians. All health care professionals who are treating patients with an eating disorder must be keenly aware of the serious risks of suicidal behavior and of suicide in this population.