bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural Evidence of Glycoprotein Assembly in Cellular Membrane Compartments prior to Alphavirus Budding
Authors: Soonsawad Pan , Xing Li , Milla Emerson , Espinoza Juan M. , Kawano Masaaki , Marko Michael , Hsieh Chyongere , Furukawa Hiromitsu , Kawasaki Masahiro , Weerachatyanukul Wattana , Srivastava Ranjana , Barnett Susan W. , Srivastava Indresh K. , Cheng R. Holland
Published: August 2010

Membrane glycoproteins of alphavirus play a critical role in the assembly and budding of progeny virions. However, knowledge regarding transport of viral glycoproteins to the plasma membrane is obscure. In this study, we investigated the role of cytopathic vacuole type II (CPV-II) through
in situ
electron tomography of alphavirus-infected cells. The results revealed that CPV-II contains viral glycoproteins arranged in helical tubular arrays resembling the basic organization of glycoprotein trimers on the envelope of the mature virions. The location of CPV-II adjacent to the site of viral budding suggests a model for the transport of structural components to the site of budding. Thus, the structural characteristics of CPV-II can be used in evaluating the design of a packaging cell line for replicon production.
In Vitro
Analysis of Virus Particle Subpopulations in Candidate Live-Attenuated Influenza Vaccines Distinguishes Effective from Ineffective Vaccines
Authors: Marcus Philip I. , Ngunjiri John M. , Sekellick Margaret J. , Wang Leyi , Lee Chang-Won
Published: August 2010

Two effective (
vac
+
) and two ineffective (
vac
−
) candidate live-attenuated influenza vaccines (LAIVs) derived from naturally selected genetically stable variants of A/TK/OR/71-delNS1[1-124] (H7N3) that differed only in the length and kind of amino acid residues at the C terminus of the nonstructural NS1 protein were analyzed for their content of particle subpopulations. These subpopulations included total physical particles (measured as hemagglutinating particles [HAPs]) with their subsumed biologically active particles of infectious virus (plaque-forming particles [PFPs]) and different classes of noninfectious virus, namely, interferon-inducing particles (IFPs), noninfectious cell-killing particles (niCKPs), and defective interfering particles (DIPs). The
vac
+
variants were distinguished from the
vac
−
variants on the basis of their content of viral subpopulations by (i) the capacity to induce higher quantum yields of interferon (IFN), (ii) the generation of an unusual type of IFN-induction dose-response curve, (iii) the presence of IFPs that induce IFN more efficiently, (iv) reduced sensitivity to IFN action, and (v) elevated rates of PFP replication that resulted in larger plaques and higher PFP and HAP titers. These
in vitro
analyses provide a benchmark for the screening of candidate LAIVs and their potential as effective vaccines. Vaccine design may be improved by enhancement of attributes that are dominant in the effective (
vac
+
) vaccines.
Open Reading Frame E3-10.9K of Subspecies B1 Human Adenoviruses Encodes a Family of Late Orthologous Proteins That Vary in Their Predicted Structural Features and Subcellular Localization
Authors: Frietze Kathryn M. , Campos Samuel K. , Kajon Adriana E.
Published: August 2010

Subspecies B1 human adenoviruses (HAdV-B1s) are important causative agents of acute respiratory disease, but the molecular bases of their distinct pathobiology are still poorly understood. Marked differences in genetic content between HAdV-B1s and the well-characterized HAdV-Cs that may contribute to distinct pathogenic properties map to the E3 region. Between the highly conserved E3-19K and E3-10.4K/RIDα open reading frames (ORFs), and in the same location as the HAdV-C ADP/E3-11.6K ORF, HAdV-B1s carry ORFs E3-20.1K and E3-20.5K and a polymorphic third ORF, designated E3-10.9K, that varies in the size of its predicted product among HAdV-B1 serotypes and genomic variants. As an initial effort to define the function of the E3-10.9K ORF, we carried out a biochemical characterization of E3-10.9K-encoded orthologous proteins and investigated their expression in infected cells. Sequence-based predictions suggested that E3-10.9K orthologs with a hydrophobic domain are integral membrane proteins. Ectopically expressed, C-terminally tagged (with enhanced green fluorescent protein [EGFP]) E3-10.9K and E3-9K localized primarily to the plasma membrane, while E3-7.7K localized primarily to a juxtanuclear compartment that could not be identified. EGFP fusion proteins with a hydrophobic domain were N and O glycosylated. EGFP-tagged E3-4.8K, which lacked the hydrophobic domain, displayed diffuse cellular localization similar to that of the EGFP control. E3-10.9K transcripts from the major late promoter were detected at late time points postinfection. A C-terminally hemagglutinin-tagged version of E3-9K was detected by immunoprecipitation at late times postinfection in the membrane fraction of mutant virus-infected cells. These data suggest a role for ORF E3-10.9K-encoded proteins at late stages of HAdV-B1 replication, with potentially important functional implications for the documented ORF polymorphism.
Partial Functional Rescue of
Helicoverpa armigera
Single Nucleocapsid Nucleopolyhedrovirus Infectivity by Replacement of F Protein with GP64 from
Autographa californica
Multicapsid Nucleopolyhedrovirus
Authors: Wang Manli , Yin Feifei , Shen Shu , Tan Ying , Deng Fei , Vlak Just M. , Hu Zhihong , Wang Hualin
Published: August 2010

Two distinct envelope fusion proteins (EFPs) (GP64 and F) have been identified in members of the
Baculoviridae
family of viruses. F proteins are found in group II nucleopolyhedroviruses (NPVs) of alphabaculoviruses and in beta- and deltabaculoviruses, while GP64 occurs only in group I NPVs of alphabaculoviruses. It was proposed that an ancestral baculovirus acquired the
gp64
gene that conferred a selective advantage and allowed it to evolve into group I NPVs. The F protein is a functional analogue of GP64, as evidenced from the rescue of
gp64
-null
Autographa californica
multicapsid nucleopolyhedrovirus (MNPV) (AcMNPV) by F proteins from group II NPVs or from betabaculoviruses. However, GP64 failed to rescue an F-null
Spodoptera exigua
MNPV (SeMNPV) (group II NPV). Here, we report the successful generation of an infectious
gp64
-rescued group II NPV of
Helicoverpa armigera
(vHaBacΔF-gp64). Viral growth curve assays and quantitative real-time PCR (Q-PCR), however, showed substantially decreased infectivity of vHaBacΔF-gp64 compared to the HaF rescue control virus vHaBacΔF-HaF. Electron microscopy further showed that most vHaBacΔF-gp64 budded viruses (BV) in the cell culture supernatant lacked envelope components and contained morphologically aberrant nucleocapsids, suggesting the improper BV envelopment or budding of vHaBacΔF-gp64. Bioassays using pseudotyped viruses with a reintroduced
polyhedrin
gene showed that GP64-pseudotyped
Helicoverpa armigera
single nucleocapsid nucleopolyhedrovirus (HearNPV) significantly delayed the mortality of infected
H. armigera
larvae.
The Carboxy-Terminal Segment of the Human Cytomegalovirus DNA Polymerase Accessory Subunit UL44 Is Crucial for Viral Replication
Authors: Silva Laurie A. , Loregian Arianna , Pari Gregory S. , Strang Blair L. , Coen Donald M.
Published: August 2010

The amino-terminal 290 residues of UL44, the presumed processivity factor of human cytomegalovirus DNA polymerase, possess all of the established biochemical activities of the full-length protein, while the carboxy-terminal 143 residues contain a nuclear localization signal (NLS). We found that although the amino-terminal domain was sufficient for origin-dependent synthesis in a transient-transfection assay, the carboxy-terminal segment was crucial for virus replication and for the formation of DNA replication compartments in infected cells, even when this segment was replaced with a simian virus 40 NLS that ensured nuclear localization. Our results suggest a role for this segment in viral DNA synthesis.
HLA-Cw*03-Restricted CD8+T-Cell Responses Targeting the HIV-1 Gag Major Homology Region Drive Virus Immune Escape and Fitness Constraints Compensated for by Intracodon Variation
Authors: Honeyborne Isobella , Codoñer Francisco M. , Leslie Alasdair , Tudor-Williams Gareth , Luzzi Graz , Ndung'u Thumbi , Walker Bruce D. , Goulder Philip J. , Prado Julia G.
Published: August 2010

The potential importance of HLA-C-restricted CD8+cytotoxic T lymphocytes (CTL) in HIV infection remains undetermined. We studied the dominant HLA-Cw*03-restricted CTL response to YVDRFFKTL296-304(YL9), within the conserved major homology region (MHR) of the Gag protein, in 80 HLA-Cw*03-positive individuals with chronic HIV infection to better define the efficacy of the YL9 HLA-C-restricted response. The HLA-Cw*03 allele is strongly associated with HIV sequence changes from Thr-303 to Val, Ile, or Ala at position 8 within the YL9 epitope (P= 1.62 × 10−10).In vitrostudies revealed that introduction of the changes T303I and T303A into the YL9 epitope both significantly reduced CTL recognition and substantially reduced the viral replicative capacity. However, subsequent selection of the Val-303 variant, via intracodon variation from Ile-303 (I303V) or Ala-303 (A303V), restored both viral fitness and CTL recognition, as supported by ourin vivodata. These results illustrate that HLA-C-restricted CTL responses are capable of driving viral immune escape within Gag, but in contrast to what was previously described for HLA-B-restricted Gag escape mutants, the common Cw*03-Gag-303V variant selected resulted in no detectable benefit to the host.
Novel Nipah Virus Immune-Antagonism Strategy Revealed by Experimental and Computational Study
Authors: Seto Jeremy , Qiao Liang , Guenzel Carolin A. , Xiao Sa , Shaw Megan L. , Hayot Fernand , Sealfon Stuart C.
Published: August 2010

Nipah virus is an emerging pathogen that causes severe disease in humans. It expresses several antagonist proteins that subvert the immune response and that may contribute to its pathogenicity. Studies of its biology are difficult due to its high pathogenicity and requirement for biosafety level 4 containment. We integrated experimental and computational methods to elucidate the effects of Nipah virus immune antagonists. Individual Nipah virus immune antagonists (phosphoprotein and V and W proteins) were expressed from recombinant Newcastle disease viruses, and the responses of infected human monocyte-derived dendritic cells were determined. We developed an ordinary differential equation model of the infectious process that that produced results with a high degree of correlation with these experimental results. In order to simulate the effects of wild-type virus, the model was extended to incorporate published experimental data on the time trajectories of immune-antagonist production. These data showed that the RNA-editing mechanism utilized by the wild-type Nipah virus to produce immune antagonists leads to a delay in the production of the most effective immune antagonists, V and W. Model simulations indicated that this delay caused a disconnection between attenuation of the antiviral response and suppression of inflammation. While the antiviral cytokines were efficiently suppressed at early time points, some early inflammatory cytokine production occurred, which would be expected to increase vascular permeability and promote virus spread and pathogenesis. These results suggest that Nipah virus has evolved a unique immune-antagonist strategy that benefits from controlled expression of multiple antagonist proteins with various potencies.
Pathogenesis and Immune Response of Crimean-Congo Hemorrhagic Fever Virus in a STAT-1 Knockout Mouse Model
Authors: Bente Dennis A. , Alimonti Judie B. , Shieh Wun-Ju , Camus Gaëlle , Ströher Ute , Zaki Sherif , Jones Steven M.
Published: August 2010

Tick-borne Crimean-Congo hemorrhagic fever virus (CCHFV) causes a severe hemorrhagic syndrome in humans but not in its vertebrate animal hosts. The pathogenesis of the disease is largely not understood due to the lack of an animal model. Laboratory animals typically show no overt signs of disease. Here, we describe a new small-animal model to study CCHFV pathogenesis that manifests clinical disease, similar to that seen in humans, without adaptation of the virus to the host. Our studies revealed that mice deficient in the STAT-1 signaling molecule were highly susceptible to infection, succumbing within 3 to 5 days. After CCHFV challenge, mice exhibited fever, leukopenia, thrombocytopenia, and highly elevated liver enzymes. Rapid viremic dissemination and extensive replication in visceral organs, mainly in liver and spleen, were associated with prominent histopathologic changes in these organs. Dramatically elevated proinflammatory cytokine levels were detected in the blood of the animals, suggestive of a cytokine storm. Immunologic analysis revealed delayed immune cell activation and intensive lymphocyte depletion. Furthermore, this study also demonstrated that ribavirin, a suggested treatment in human cases, protects mice from lethal CCHFV challenge. In conclusion, our data demonstrate that the interferon response is crucial in controlling CCHFV replication in this model, and this is the first study that offers an in-depth
in vivo
analysis of CCHFV pathophysiology. This new mouse model exhibits key features of fatal human CCHF, proves useful for the testing of therapeutic strategies, and can be used to study virus attenuation.
CD8
+
T Cell Recognition of Cryptic Epitopes Is a Ubiquitous Feature of AIDS Virus Infection
Authors: Maness Nicholas J. , Walsh Andrew D. , Piaskowski Shari M. , Furlott Jessica , Kolar Holly L. , Bean Alexander T. , Wilson Nancy A. , Watkins David I.
Published: August 2010

Vaccines designed to elicit AIDS virus-specific CD8
+
T cells should engender broad responses. Emerging data indicate that alternate reading frames (ARFs) of both human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) encode CD8
+
T cell epitopes, termed cryptic epitopes. Here, we show that SIV-specific CD8
+
T cells from SIV-infected rhesus macaques target 14 epitopes in eight ARFs during SIV infection. Animals recognized up to five epitopes, totaling nearly one-quarter of the anti-SIV responses. The epitopes were targeted by high-frequency responses as early as 2 weeks postinfection and in the chronic phase. Hence, previously overlooked ARF-encoded epitopes could be important components of AIDS vaccines.
Lambda Interferon Is the Predominant Interferon Induced by Influenza A Virus Infection
In Vivo
Authors: Jewell Nancy A. , Cline Troy , Mertz Sara E. , Smirnov Sergey V. , Flaño Emilio , Schindler Christian , Grieves Jessica L. , Durbin Russell K. , Kotenko Sergei V. , Durbin Joan E.
Published: August 2010

The type I alpha/beta interferons (IFN-α/β) are known to play an important role in host defense against influenza A virus infection, but we have now discovered that the recently identified type III IFNs (IFN-λ) constitute the major response to intranasal infection with this virus. Type III IFNs were present at much higher levels than type I IFNs in the lungs of infected mice, and the enhanced susceptibility of STAT2
−/−
animals demonstrated that only signaling through the IFN-α/β or IFN-λ pathways was sufficient to mediate protection. This finding offers a possible explanation for the similar levels of antiviral protection found in wild-type (WT) mice and in animals lacking a functional type I IFN receptor (IFNAR
−/−
) but also argues that our current understanding of type III IFN induction is incomplete. While murine IFN-λ production is thought to depend on signaling through the type I IFN receptor, we demonstrate that intranasal influenza A virus infection leads to the robust type III IFN induction in the lungs of both WT and IFNAR
−/−
mice. This is consistent with previous studies showing that IFNAR-mediated protection is redundant for mucosal influenza virus infection and with data showing that the type III IFN receptor is expressed primarily by epithelial cells. However, the overlapping effects of these two cytokine families are limited by their differential receptor expression, with a requirement for IFN-α/β signaling in combating systemic disease.
Cerebral revascularization for ischemic disease in the 21st century
Authors: Bambakidis Nicholas C , Chowdhry Shakeel A
Published: August 2010

Shortly after the first extracranial to intracranial (EC–IC) carotid artery bypass was performed by Yasargil in 1967 for internal carotid artery occlusion, cerebral revascularization became widely accepted in the neurosurgical field, and the procedures became increasingly used as practitioners began to master the technical aspects of the surgery. The procedures were performed for intracranial arterial stenosis and occlusion and used as an adjunct in the treatment of large aneurysms and skull base tumors. The results of the EC–IC bypass group trial in 1985 were surprising to many and sobering to all; EC–IC bypass for stenosis or occlusion of the high internal carotid artery or middle cerebral artery did not decrease the risk of subsequent stroke compared with medical management. Rather, the incidence of stroke increased, and the events were noted to occur sooner than with medical therapy alone. Despite the known limitations of this landmark study, the number of EC–IC bypass procedures fell precipitously over the ensuing decades. Despite this significant setback, cerebral revascularization is not obsolete. This article revisits the sequence of events leading to the rise of revascularization surgery and recaps the impact of the EC–IC bypass trial. The limitations of the trial are discussed, as are current studies evaluating the efficacy of cerebrovascular bypass procedures for symptomatic carotid occlusive disease. The authors review the accepted indications for bypass surgery in the early 21st century.
Trends in blood lead levels in UK workers, 1995–2007
Authors: Morton Jackie , Cotton Richard , Cocker John , Warren Nicholas D
Published: August 2010

Objectives

This study evaluated blood lead data (including zinc protoporphyrin (ZPP) and haemoglobin levels) collected at the UK's Health and Safety Laboratory (HSL) in order to determine temporal changes in occupational exposure to lead between 1995 and 2007.

Methods

A total of 20 889 blood lead measurements and accompanying ZPP and haemoglobin results from 8810 workers at 972 companies from routine samples received by HSL over the period 1995–2007 were analysed. Time trends in blood lead levels for each industry sector were estimated using Bayesian mixed effects modelling.

Results

Reductions in median blood levels over the period 1995–2007 were seen in every sector except for those samples forwarded by occupational health providers, and range from 1.6% per year for workers in the smelting industry to 12% per year for workers in pottery and glazing industries. An overall reduction of 3.1% per year across all industries was determined. The percentage of results above the current UK suspension limit of 60 μg/dl fell from 4.8% in 1995 to 0.6% in 2007. ZPP and blood lead exhibited a strong association, but no significant correlation was found between blood lead and haemoglobin.

Conclusions

Occupational exposure to lead has fallen across UK industries in recent years, although it remains substantially above background levels. There is evidence that many workers are exposed to elevated lead levels over a long period of time and this deserves renewed consideration now that inorganic lead has been reclassified as a probable human carcinogen.
Cytogenotoxicity in uroepithelial cells of women exposed to mercury in a mining area
Authors: Soto-Ríos M Lourdes , Rothenberg Stephen , Gonsebatt M Eugenia , Talavera-Mendoza Oscar
Published: August 2010

Objective

To investigate biomarkers of cytogenotoxicity in women exposed to mercury in a mining area. Mercury has been associated with cytogenotoxicity in human and animal models but has not been considered carcinogenic in humans, even though genotoxic effects following exposure to inorganic mercury compounds have been observed.

Methods

A cross-sectional study and micronucleus assay in uroepithelial cells were performed in 104 women (12–84 years of age). First urine void samples were taken to determine creatinine-adjusted mercury levels in urine (HgUCr), to isolate cells and to quantify cytogenetic damage.

Results

The geometric average level for HgUCr was 4.9 μg/g (range, 0.4–85). In the generalised linear model, after controlling for other co-variables, we observed that for each 10 μg/g increase in HgUCr, the OR of developing a genotoxic effect was 2.37 (95% CI 1.79 to 2.84), while for cytotoxic damage in uroepithelial cells the OR was 1.34 (95% CI 1.10 to 1.79). These results suggest a possible association between cytogenotoxicity and HgUCr.

Conclusion

Living in a mining area with exposure to inorganic mercury and having higher mercury levels in urine increased the risk of developing uroepithelial cytogenotoxicity.
ANISOTROPIC CONSOLIDATION OF LEDA CLAY
Authors: Walker L. K. , Raymond G. P.
Published: August 2010

Under field loading conditions, the consolidation of a clay layer is likely to take place under effective principal stress ratios (σ1′/σ3′), which vary from point to point throughout the soil mass. From a consideration of idealized stress paths, an estimate is made of the effect of stress ratio on rates of volumetric strain and excess pore water pressure dissipation. These predictions are partly supported by data obtained from anisotropic consolidation tests on Leda clay, the major disagreements being due to the significant influence of structural cementation on the rate process.The experimentally observed rates of shear strain have been analyzed in terms of stress-dilatancy concepts. The plastic strain-increment ratio was shown to be a unique function of effective stress ratio, thus confirming the validity of previous work on remoulded clays. A theoretical prediction of this relationship postulated by Burland (1965) did not approximate to the experimental data, due probably to the influence of secondary deformations. The data did, however, show a relationship similar in form to that derived by Walker (1969) for the secondary deformation of remoulded kaolin.
NEW PILE FORCE GAUGE FOR ACCURATE MEASUREMENTS OF PILE BEHAVIOR DURING AND FOLLOWING DRIVING: RESEARCH NOTE
Authors: Fellenius Bengt H. , Haagen Thomas
Published: August 2010

The paper reports a new pile-force gauge based upon the principle of the vibrating wire. The gauge is intended to be driven down with a precast concrete pile and can be placed at an arbitrarily chosen depth in the pile. The impacts from the pile driving will not impair the gauge. The gauge registers the static loads and bending moments in a pile with an error not exceeding 2% of the linear measuring range. This maximum error includes the drifting of zero point and change of sensitivity with time.The design of the gauge and laboratory and full-scale tests are reported, and suitable use of the gauge is suggested.
A FLUID SETTLEMENT GAUGE: RESEARCH NOTE
Authors: Bozozuk M.
Published: August 2010

The paper describes an apparatus for determining vertical settlements by measuring the hydrostatic pressures in a flexible fluid-filled hose positioned horizontally beneath an engineering structure. The pressures are measured with a torpedo containing a pressure transducer which is pulled through the hose, enabling settlements to be measured continuously along its length. As it is withdrawn after each survey, it can be used for any number of installations.
FARADAY AND COTTON–MOUTON ROTATIONS IN RELATIVISTIC MEDIUM
Authors: ROJAS H. P. , QUERTS E. R.
Published: August 2010

The rotation of the polarization vector for light propagating in an external constant magnetic field B in relativistic media is discussed in the two main cases: Faraday and Cotton–Mouton effects. Faraday rotation is circular and arises whenever the medium is not invariant under charge conjugation, whereas Cotton–Mouton rotation arises due to the breaking of the space symmetry in any transparent medium, and describes a sort of ellipse whose axes vary periodically in time from zero to two maximum values. The discussion starts from the expressions for the photon energy eigenvalues in vacuum as well as in a relativistic electron–positron gas, which remain valid in the low energy, low density limits. Values for the rotation frequencies are estimated in some specific cases. Our studies might be of interest both in experimental studies about light propagation in ultrahigh vacuum, as well as in astrophysics.
FROM CRUST TO CORE: A BRIEF REVIEW OF QUARK MATTER IN NEUTRON STARS
Authors: WEBER F. , HAMIL O. , MIMURA K. , NEGREIROS R.
Published: August 2010

This paper provides a short overview of the multifaceted, possible role of quark matter for compact stars (neutron stars and strange quark matter stars). We began with a variational investigation of the maximum possible energy densities in the cores of neutron stars. This is followed by a brief discussion of the possible existence of quark matter in the cores of neutron stars and how such matter could manifest itself in neutron star observables. The possible presence of color superconducting strange quark matter nuggets in the crusts of neutron stars is reviewed next, and their impact on the pycnonuclear reaction rates in the crusts of neutron stars is discussed. The second part of the paper discusses the impact of ultra-strong electric fields on the bulk properties of strange quark matter stars and presents results of a preliminary study that models the thermal evolution of radio-quiet, X-ray bright, central compact objects (CCOs).
THE MILNE SPACETIME AND THE HADRONIC RINDLER HORIZON
Authors: CULETU H.
Published: August 2010

A direct relation between the time-dependent Milne geometry and the Rindler spacetime is shown. Milne's metric corresponds to the region beyond Rindler's event horizon (in the wedge t ≻ |x|). We point out that inside a Schwarzschild black hole and near its horizon, the metric may be Milne's flat metric.

It was found that the shear tensor associated to a congruence of fluid particles of the RHIC expanding fireball has the same structure as that corresponding to the anisotropic fluid from the black hole interior, even though the latter geometry is curved.
ON PHOTON PARAMAGNETISM AND VACUUM DECAY IN A MAGNETIC FIELD
Authors: PÉREZ ROJAS H. , RODRÍGUEZ QUERTS E.
Published: August 2010

Previous results from the authors2 concerning the rising of a tiny photon anomalous paramagnetic moment μγ, that is due to its interaction with a magnetized virtual electron–positron background, are complemented and discussed. It is shown that in the region beyond the first threshold, where photons may decay into electron–positron pairs, for magnetic fields large enough, the vacuum becomes unstable and decays also into electron–positron pairs.
POSSIBLE LOW ENERGY MANIFESTATIONS OF STRINGS AND GRAVITY
Authors: ANTONIADIS I.
Published: August 2010

Lowering the string scale in the TeV region provides a theoretical framework for solving the mass hierarchy problem and unifying all interactions. The apparent weakness of gravity can then be accounted by the existence of large internal dimensions, in the submillimeter region, and transverse to a braneworld where our universe must be confined. The author reviews the main properties of this scenario and its implications for observations at both particle colliders, and in non-accelerator gravity experiments.
THE INTERACTION OF ρ AND K+ MESONS WITH MATTER
Authors: AICHELIN J. , HARTNACK C. , LEIFELS Y. , OESCHLER H. , VOGEL S.
Published: August 2010

We review in this contribution the information we can obtain from heavy-ion experiments about the interaction of mesons with matter. We demonstrate that the vector mesons seen in experiments come predominantly from low densities. Kaons offer a better opportunity but most of the presently available experimental observables do not allow to analyze separately the three essential unknown quantities: the kaon production cross-section in the medium, the K+N potential interaction at finite densities and temperatures and the kaon (elastic or charge exchange) rescattering cross-section in the medium. We propose a measurement which almost exclusively tests the K+N potential.
CHARGE INFLUENCE ON MINI BLACK HOLE'S CROSS SECTION
Authors: CARAÇA R. S. , MALHEIRO M.
Published: August 2010

In this work we study the electric charge effect on the cross section production of charged mini black holes (MBH) in accelerators. We analyze the charged MBH solution using the fat brane approximation in the context of the ADD model. The maximum charge–mass ratio condition for the existence of a horizon radius is discussed. We show that the electric charge causes a decrease in this radius and, consequently, in the cross section. This reduction is negligible for protons and light-ions but can be important for heavy-ions.
HOT AND COMPACT STELLAR OBJECTS AND THEIR ADIABATIC INDEX
Authors: CASALI R. H. , MENEZES D. P.
Published: August 2010

The adiabatic index of pulsars formed by hadronic or quarkionic matter, with and without trapped neutrinos, is calculated for two values of the entropy per baryon S = 0, 2 kB/baryon. The nonlinear Walecka model1 is used to describe hadronic stars, and the MIT bag model2 to describe quark stars. Particle fractions for each case are obtained and the appearance of particles are shown to coincide with drops in the adiabatic index.
SPECTRUM OF SCREENING MASSES FOR SU(2) GAUGE THEORY: UNIVERSALITY CLASS
Authors: COSTA R. S. , DUARTE S. B. , CHIAPPARINI M. , MENDES T.
Published: August 2010

In this work we study the spectrum of the lowest screening masses for Yang–Mills theories on the lattice. We used the SU(2) gauge group in (3 + 1) dmensions. We adopted the multiple exponential method and the so-called "variational" method, in order to detect possible excited states. The calculations were done near the critical temperature of the confinement-deconfinement phase transition. We obtained values for the ratios of the screening masses consistent with predictions from universality arguments. A Monte Carlo evolution of the screening masses in the gauge theory confirms the validity of the predictions.
NONPERTURBATIVE HQET AT ORDER 1/m
Authors: BLOSSIER B. , VON HIPPEL G. , GARRON N. , MENDES T.
Published: August 2010

We summarize the first results for masses and decay constants of bottom-strange (pseudo-scalar and vector) mesons from nonperturbatively renormalized heavy-quark effective theory (HQET), using lattice-QCD simulations in the quenched approximation.
HEAVY-ION AND ASTROPHYSICS CONSTRAINTS IN THE PARAMETRIC COUPLING MODEL
Authors: GROHMANN M. , VASCONCELLOS C. A. Z. , MARRANGHELLO G. F. , FERNÁNDEZ F.
Published: August 2010

The relativistic parametric coupling model is used here to describe global static properties of nuclear matter and neutron stars. Using recent observational data related to neutron star properties and experimental results of heavy-ion collisions, we review some properties of the effective model and we impose this way new constraints on its coupling constants. Then we analyze the consequences on already known parameters of nuclear matter, i.e., the compression modulus, the effective nucleon mass and the maximum neutron star mass predicted by integrating the Tolman–Oppenheimer–Volkoff equations. We make use of recent data on flow analysis to constrain the parameters of the theory and to achieve this goal, and have explored the parametric coupling model in a wide range of parameters. Our predictions for the compression modulus of nuclear matter and for the maximum mass of neutron stars are in good agreement with the observational data.
NATURALNESS, ISOSPIN BREAKING IN NUCLEAR MATTER AND THE OKAMOTO–NOLEN–SCHIFFER ANOMALY
Authors: RAZEIRA M. , MESQUITA A. , VASCONCELLOS C. A. Z. , FERNÁNDEZ F.
Published: August 2010

A recently developed relativistic theory for nuclear matter, which shows consistency with the concept of naturalness and conservation of chiral symmetry, is applied to the description of the Okamoto–Nolen–Schiffer anomaly. The results of our study show significant improvements in the description of the anomaly when compared to the corresponding results of other authors. In particular, our predictions for the Okamoto–Nolen–Schiffer anomaly include the known anomalous growth, namely that the anomaly not necessarily grow with the nuclear mass, since the anomaly is lower, for instance, for the nuclei 39 C and 39 K when compared to the 17 F and 17 O nuclei. As far as we know, this trend was not described by any other model found in the literature.
EFFECTS OF THE EXISTENCE OF A MIXED PHASE IN HYBRID NEUTRON STARS
Authors: PAOLI M. G. , MENEZES D. P.
Published: August 2010

In this work we investigate the structure of hybrid stars composed of a hadron phase described by the nonlinear Walecka model and a quark phase described by the Nambu–Jona–Lasinio model. Two constructions are studied: the first one considers the existence of a mixed phase at intermediate stellar densities, between the density where matter is composed of hadrons and the density where matter is composed of quarks. The second construction implies the inexistence of this mixed phase. In this case, the hadron and the quark phases are in direct contact.
DYNAMIC OPTIMAL BUDGET ALLOCATION FOR INTEGRATED MARKETING CONSIDERING PERSISTENCE
Authors: AI SHIZHONG , DU RONG , HU QIYING
Published: August 2010

Aiming at forming dynamic optimal integrated marketing policies, we build a budget allocation model considering both current effects and sustained ones. The model includes multiple time periods and multiple marketing tools which interact through a common resource pool as well as through delayed cross influences on each other's sales, reflecting the nature of "integrated marketing" and its dynamics. In our study, marginal analysis is used to illuminate the structure of optimal policy. We derive some analytical results which have managerial implications and give strong supports to empirical actions in marketing. Our results are consistent with those in some resource allocations problems, but different from those in the others. We illustrate the application of our model by demonstrating a case of a beauty salon in Xi'an, China. We show how to optimally allocate budgets between different sales promotion components so as to maximize the profits of beauty product and service companies.
Abl activation regulates the dissociation of CAS from cytoskeletal vimentin by modulating CAS phosphorylation in smooth muscle
Authors: Jia Li , Tang Dale D.
Published: August 2010

Abl is a nonreceptor tyrosine kinase that is required for smooth muscle contraction. However, the mechanism by which Abl regulates smooth muscle contraction is not completely understood. In the present study, Abl underwent phosphorylation at Tyr412 (an index of Abl activation) in smooth muscle in response to contractile activation. Treatment with a cell-permeable decoy peptide, but not the control peptide, attenuated Abl phosphorylation during contractile stimulation. Treatment with the decoy peptide did not affect the association of Abl with the cytoskeletal protein vinculin and the spatial location of vinculin in smooth muscle. Inhibition of Abl phosphorylation by the decoy peptide attenuated the agonist-induced phosphorylation of Crk-associated substrate (CAS), an adapter protein participating in the signaling processes that regulate force development in smooth muscle. Additionally, previous studies have shown that contractile stimulation triggers the dissociation of CAS from the vimentin network, which is important for cytoskeletal signaling and contraction in smooth muscle. In this report, the decrease in the amount of CAS in cytoskeletal vimentin in response to contractile activation was reversed by the Abl inhibition with the decoy peptide. Moreover, force development and the enhancement of F-actin-to-G-actin ratios (an indication of actin polymerization) upon contractile activation were also attenuated by the Abl inhibition. However, myosin phosphorylation induced by contractile activation was not affected by the inhibition of Abl. These results suggest that Abl regulates the dissociation of CAS from the vimentin network, actin polymerization, and contraction by modulating CAS phosphorylation in smooth muscle.
Impact of viral-mediated IGF-I gene transfer on skeletal muscle following cast immobilization
Authors: Stevens-Lapsley Jennifer E. , Ye Fan , Liu Min , Borst Stephen E. , Conover Christine , Yarasheski Kevin E. , Walter Glenn A. , Sweeney H. Lee , Vandenborne Krista
Published: August 2010

Insulin-like growth factor I (IGF-I) is a potent myogenic factor that plays a critical role in muscle regeneration and muscle hypertrophy. The purpose of this study was to evaluate the effect of IGF-I overexpression on the recovery of muscle size and function during reloading/reambulation after a period of cast immobilization in predominantly fast twitch muscles. In addition, we investigated concomitant molecular responses in IGF-I receptor and binding proteins (BPs). Recombinant adeno-associated virus vector for IGF-I (rAAV-IGF-IA) was injected into the anterior compartment of one of the hindlimbs of young (3 wk) C57BL6 female mice. At 20 wk of age, both hindlimbs were cast immobilized in a shortened position for 2 wk to unload the tibialis anterior (TA) and extensor longus digitorum (EDL) muscles. The TA and EDL muscles were removed bilaterally after 2 wk of cast immobilization and after 1 and 3 wk of free cage reambulation. Increases in IGF-I mRNA and protein levels with IGF-I overexpression were associated with significant increases in muscle wet weight, fiber size, and tetanic force, although overexpression did not protect against cast immobilization-induced muscle atrophy. After 1 wk of reambulation, evidence of enhanced muscle regeneration was noted in IGF-I-overexpressing muscles with an increased prevalence of central nuclei, embryonic myosin, and Pax7 positive fibers. We also observed larger relative gains in muscle size (wet weight and fiber area), but not force, during the 3-wk reambulation period in hindlimb muscles overexpressing IGF-I compared with contralateral control legs. Changes in IGFBP-5 mRNA expression during cast immobilization and reambulation paralleled those of IGF-I, whereas IGFBP-3 expression changed inversely to IGFBP-5.
Allogenic fetal membrane-derived mesenchymal stem cells contribute to renal repair in experimental glomerulonephritis
Authors: Tsuda Hidetoshi , Yamahara Kenichi , Ishikane Shin , Otani Kentaro , Nakamura Atsuhiro , Sawai Kazutomo , Ichimaru Naotsugu , Sada Masaharu , Taguchi Akihiko , Hosoda Hiroshi , Tsuji Masahiro , Kawachi Hiroshi , Horio Masaru , Isaka Yoshitaka , Kangawa Kenji , Takahara Shiro , Ikeda Tomoaki
Published: August 2010

Mesenchymal stem cells (MSC) have been reported to be an attractive therapeutic cell source for the treatment of renal diseases. Recently, we reported that transplantation of allogenic fetal membrane-derived MSC (FM-MSC), which are available noninvasively in large amounts, had a therapeutic effect on a hindlimb ischemia model (Ishikane S, Ohnishi S, Yamahara K, Sada M, Harada K, Mishima K, Iwasaki K, Fujiwara M, Kitamura S, Nagaya N, Ikeda T. Stem Cells 26: 2625–2633, 2008). Here, we investigated whether allogenic FM-MSC administration could ameliorate renal injury in experimental glomerulonephritis. Lewis rats with anti-Thy1 nephritis intravenously received FM-MSC obtained from major histocompatibility complex-mismatched ACI rats (FM-MSC group) or a PBS (PBS group). Nephritic rats exhibited an increased urinary protein excretion in the PBS group, whereas the FM-MSC group rats had a significantly lower level of increase ( P < 0.05 vs. PBS group). FM-MSC transplantation significantly reduced activated mesangial cell (MC) proliferation, glomerular monocyte/macrophage infiltration, mesangial matrix accumulation, as well as the glomerular expression of inflammatory or extracellular matrix-related genes including TNF-α, monocyte chemoattractant protein 1 (MCP-1), type I collagen, TGF-β, type 1 plasminogen activator inhibitor (PAI-1) ( P < 0.05 vs. PBS group). In vitro, FM-MSC-derived conditioned medium significantly attenuated the expression of TNF-α and MCP-1 in rat MC through a prostaglandin E2-dependent mechanism. These data suggest that transplanted FM-MSC contributed to the healing process in injured kidney tissue by producing paracrine factors. Our results indicate that allogenic FM-MSC transplantation is a potent therapeutic strategy for the treatment of acute glomerulonephritis.
Intrarenal suppression of angiotensin II type 1 receptor binding molecule in angiotensin II-infused mice
Authors: Wakui Hiromichi , Tamura Kouichi , Matsuda Miyuki , Bai Yunzhe , Dejima Toru , Shigenaga Atsu-ichiro , Masuda Shin-ichiro , Azuma Koichi , Maeda Akinobu , Hirose Tomonori , Ishigami Tomoaki , Toya Yoshiyuki , Yabana Machiko , Minamisawa Susumu , Umemura Satoshi
Published: August 2010

ATRAP [ANG II type 1 receptor (AT1R)-associated protein] is a molecule which directly interacts with AT1R and inhibits AT1R signaling. The aim of this study was to examine the effects of continuous ANG II infusion on the intrarenal expression and distribution of ATRAP and to determine the role of AT1R signaling in mediating these effects. C57BL/6 male mice were subjected to vehicle or ANG II infusions at doses of 200, 1,000, or 2,500 ng·kg−1·min−1for 14 days. ANG II infusion caused significant suppression of ATRAP expression in the kidney but did not affect ATRAP expression in the testis or liver. Although only the highest ANG II dose (2,500 ng·kg−1·min−1) provoked renal pathological responses, such as an increase in the mRNA expression of angiotensinogen and the α-subunit of the epithelial sodium channel, ANG II-induced decreases in ATRAP were observed even at the lowest dose (200 ng·kg−1·min−1), particularly in the outer medulla of the kidney, based on immunohistochemical staining and Western blot analysis. The decrease in renal ATRAP expression by ANG II infusion was prevented by treatment with the AT1R-specific blocker olmesartan. In addition, the ANG II-mediated decrease in renal ATRAP expression through AT1R signaling occurred without an ANG II-induced decrease in plasma membrane AT1R expression in the kidney. On the other hand, a transgenic model increase in renal ATRAP expression beyond baseline was accompanied by a constitutive reduction of renal plasma membrane AT1R expression and by the promotion of renal AT1R internalization as well as the decreased induction of angiotensinogen gene expression in response to ANG II. These results suggest that the plasma membrane AT1R level in the kidney is modulated by intrarenal ATRAP expression under physiological and pathophysiological conditions in vivo.
Modulation of Firing Rate by Background Synaptic Noise Statistics in Rat Visual Cortical Neurons
Authors: Sceniak Michael P. , Sabo Shasta L.
Published: August 2010

It has been shown previously that background synaptic noise modulates the response gain of neocortical neurons. However, the role of the statistical properties of the noise in modulating firing rate is not known. Here, the dependence of firing rate on the statistical properties of the excitatory to inhibitory balance (EI) in cortical pyramidal neurons was studied. Excitatory glutamatergic and inhibitory GABAergic synaptic conductances were simulated as two stochastic processes and injected into individual neurons in vitro through use of the dynamic-clamp system. Response gain was significantly modulated as a function of the statistical interactions between excitatory and inhibitory synaptic conductances. Firing rates were compared for noisy synaptic conductance steps by varying either the EI correlation or the relative delay between correlated E and I. When inhibitory synaptic conductances exhibited a short temporal delay (5 ms) relative to correlated excitatory synaptic conductances, the response gain was increased compared with noise with no temporal delay but with an equivalent degree of correlation. The dependence of neuronal firing rate on the EI delay of the noisy background synaptic conductance suggests that individual excitatory pyramidal neurons are sensitive to the EI balance of the synaptic conductance. Therefore the statistical EI interactions encoded within the synaptic subthreshold membrane fluctuations are able to modulate neuronal firing properties.
Supplementary Eye Field Encodes Option and Action Value for Saccades With Variable Reward
Authors: So Na-Young , Stuphorn Veit
Published: August 2010

We recorded neuronal activity in the supplementary eye field (SEF) while monkeys made saccades to targets that yielded rewards of variable amount and uncertainty of delivery. Some SEF cells (29%) represented the anticipated value of the saccade target. These neurons encoded the value of the reward option but did not reflect the action necessary to obtain the reward. A plurality of cells (45%) represented both saccade direction and value. These neurons reflect action value, i.e., the value that is expected to follow from a specific saccade. Other cells (13%) represented only saccade direction. The SEF neurons matched the monkey's risk-seeking behavior by responding more strongly to the uncertain reward options than would be expected based on their response to the sure options and the cued outcome probability. Thus SEF neurons represented subjective, not expected, value. Across the SEF population, option-value signals developed early, ∼120 ms prior to saccade execution. Action-value and saccade direction signals developed ∼60 ms later. These results suggest that the SEF is involved in transforming option-value signals into action-value signals. However, in contrast to other oculomotor neurons, SEF neurons did not reach a constant level of activity before saccade onset. Instead the activity level of many (52%) SEF neurons still reflected value at the time just before saccade initiation. This suggests that SEF neurons guide the selection of a saccade based on value information but do not participate in the initiation of that saccade.
Auditory Nerve Fibers Excite Targets Through Synapses That Vary in Convergence, Strength, and Short-Term Plasticity
Authors: Cao Xiao-Jie , Oertel Donata
Published: August 2010

Auditory nerve fibers are the major source of excitation to the three groups of principal cells of the ventral cochlear nucleus (VCN), bushy, T stellate, and octopus cells. Shock-evoked excitatory postsynaptic currents (eEPSCs) in slices from mice showed systematic differences between groups of principal cells, indicating that target cells contribute to determining pre- and postsynaptic properties of synapses from spiral ganglion cells. Bushy cells likely to be small spherical bushy cells receive no more than three, most often two, excitatory inputs; those likely to be globular bushy cells receive at least four, most likely five, inputs. T stellate cells receive 6.5 inputs. Octopus cells receive >60 inputs. The N-methyl-d-aspartate (NMDA) components of eEPSCs were largest in T stellate, smaller in bushy, and smallest in octopus cells, and they were larger in neurons from younger than older mice. The average AMPA conductance of a unitary input is 22 ± 15 nS in both groups of bushy cells, <1.5 nS in octopus cells, and 4.6 ± 3 nS in T stellate cells. Sensitivity to philanthotoxin (PhTX) and rectification in the intracellular presence of spermine indicate that AMPA receptors that mediate eEPSCs in T stellate cells contain more GluR2 subunits than those in bushy and octopus cells. The AMPA components of eEPSCs were briefer in bushy (0.5 ms half-width) than in T stellate and octopus cells (0.8–0.9 ms half-width). Widening of eEPSCs in the presence of cyclothiazide (CTZ) indicates that desensitization shortens eEPSCs. CTZ-insensitive synaptic depression of the AMPA components was greater in bushy and octopus than in T stellate cells.