bluuebunny/crossref_metadata_2025 huggingface dataset:
Activation of the Interferon Response by Human Cytomegalovirus Occurs via Cytoplasmic Double-Stranded DNA but Not Glycoprotein B
Authors: DeFilippis Victor R. , Sali Tina , Alvarado David , White Laura , Bresnahan Wade , Früh Klaus J.
Published: June 2010

In vitro
infection of cells with the betaherpesvirus human cytomegalovirus (HCMV) stimulates an innate immune response characterized by phosphorylation of the transcription factor interferon regulatory factor 3 (IRF3) and subsequent expression of IRF3-dependent genes. While previous work suggests that HCMV envelope glycoprotein B is responsible for initiating this reaction, the signaling pathways stimulated by virus infection that lead to IRF3 phosphorylation have largely been uncharacterized. Recently, we identified Z DNA binding protein 1 (ZBP1), a sensor of cytoplasmic DNA, as an essential protein for this response. We now describe a human fibroblast cell line exhibiting a recessive defect that results in the absence of activation of IRF3 following treatment with HCMV but not Sendai virus or double-stranded RNA. In addition, we show that while exposure of these cells to soluble HCMV glycoprotein B is capable of triggering IRF3-dependent gene transcription, transfection of the cells with double-stranded DNA is not. Furthermore, we show that overexpression of ZBP1 in these cells reestablishes their ability to secrete interferon in response to HCMV and that multiple ZBP1 transcriptional variants exist in both wild-type and mutant cells. These results have two major implications for the understanding of innate immune stimulation by HCMV. First, they demonstrate that HCMV glycoprotein B is not the essential molecular pattern that induces an IRF3-dependent innate immune response. Second, IRF3-terminal signaling triggered by HCMV particles closely resembles that which is activated by cytoplasmic double-stranded DNA.
Elevated Cyclic AMP Levels in T Lymphocytes Transformed by Human T-Cell Lymphotropic Virus Type 1
Authors: Kress Andrea K. , Schneider Grit , Pichler Klemens , Kalmer Martina , Fleckenstein Bernhard , Grassmann Ralph
Published: June 2010

Human T-cell lymphotropic virus type 1 (HTLV-1), the cause of adult T-cell leukemia/lymphoma (ATLL), transforms CD4+T cells to permanent growth through its transactivator Tax. HTLV-1-transformed cells share phenotypic properties with memory and regulatory T cells (T-reg). Murine T-reg-mediated suppression employs elevated cyclic AMP (cAMP) levels as a key regulator. This led us to determine cAMP levels in HTLV-1-transformed cells. We found elevated cAMP concentrations as a consistent feature of all HTLV-1-transformed cell lines, includingin vitro-HTLV-1-transformed, Tax-transformed, and patient-derived cells. In transformed cells with conditional Tax expression, high cAMP levels coincided with the presence of Tax but were lost without it. However, transient ectopic expression of Tax alone was not sufficient to induce cAMP. We found specific downregulation of the cAMP-degrading phosphodiesterase 3B (PDE3B) in HTLV-1-transformed cells, which was independent of Tax in transient expression experiments. This is in line with the notion that PDE3B transcripts and cAMP levels are inversely correlated. Overexpression of PDE3B led to a decrease of cAMP in HTLV-1-transformed cells. Decreased expression of PDE3B was associated with inhibitory histone modifications at the PDE3B promoter and the PDE3B locus. In summary, Tax transformation and its continuous expression contribute to elevated cAMP levels, which may be regulated through PDE3B suppression. This shows that HTLV-1-transformed cells assume biological features of long-lived T-cell populations that potentially contribute to viral persistence.
Replacement of the Replication Factors of Porcine Circovirus (PCV) Type 2 with Those of PCV Type 1 Greatly Enhances Viral Replication
I
n
V
itro
Authors: Beach N. M. , Juhan N. M. , Cordoba L. , Meng X. J.
Published: June 2010

Porcine circovirus type 1 (PCV1), originally isolated as a contaminant of PK-15 cells, is nonpathogenic, whereas porcine circovirus type 2 (PCV2) causes an economically important disease in pigs. To determine the factors affecting virus replication, we constructed chimeric viruses by swapping open reading frame 1 (ORF1) (
rep
) or the origin of replication (Ori) between PCV1 and PCV2 and compared the replication efficiencies of the chimeric viruses in PK-15 cells. The results showed that the replication factors of PCV1 and PCV2 are fully exchangeable and, most importantly, that both the Ori and
rep
of PCV1 enhance the virus replication efficiencies of the chimeric viruses with the PCV2 backbone.
Modeling Adenovirus Latency in Human Lymphocyte Cell Lines
Authors: Zhang Yange , Huang Wen , Ornelles David A. , Gooding Linda R.
Published: June 2010

Species C adenovirus establishes a latent infection in lymphocytes of the tonsils and adenoids. To understand how this lytic virus is maintained in these cells, four human lymphocytic cell lines that support the entire virus life cycle were examined. The T-cell line Jurkat ceased proliferation and died shortly after virus infection. BJAB, Ramos (B cells), and KE37 (T cells) continued to divide at nearly normal rates while replicating the virus genome. Viral genome numbers peaked and then declined in BJAB cells below one genome per cell at 130 to 150 days postinfection. Ramos and KE37 cells maintained the virus genome at over 100 copies per cell over a comparable period of time. BJAB cells maintained the viral DNA as a monomeric episome. All three persistently infected cells lost expression of the cell surface coxsackie and adenovirus receptor (CAR) within 24 h postinfection, and CAR expression remained low for at least 340 days postinfection. CAR loss proceeded via a two-stage process. First, an initial loss of cell surface staining for CAR required virus late gene expression and a CAR-binding fiber protein even while CAR protein and mRNA levels remained high. Second, CAR mRNA disappeared at around 30 days postinfection and remained low even after virus DNA was lost from the cells. At late times postinfection (day 180), BJAB cells could not be reinfected with adenovirus, even when CAR was reintroduced to the cells via retroviral transduction, suggesting that the expression of multiple genes had been stably altered in these cells following infection.
Alpha Interferon and Not Gamma Interferon Inhibits Salmonid Alphavirus Subtype 3 Replication
In Vitro
Authors: Xu Cheng , Guo Tz-Chun , Mutoloki Stephen , Haugland Øyvind , Marjara Inderjit S. , Evensen Øystein
Published: June 2010

Salmonid alphavirus (SAV) is an emerging virus in salmonid aquaculture, with SAV-3 being the only subtype found in Norway. Until now, there has been little focus on the alpha interferon (IFN-α)-induced antiviral responses during virus infection
in vivo
or
in vitro
in fish. The possible involvement of IFN-γ in the response to SAV-3 is also not known. In this study, the two IFNs were cloned and expressed as recombinant proteins (recombinant IFN-α [rIFN-α] and rIFN-γ) and used for
in vitro
studies. SAV-3 infection in a permissive salmon cell line (TO cells) results in IFN-α and IFN-stimulated gene (ISG) mRNA upregulation. Preinfection treatment (4 to 24 h prior to infection) with salmon rIFN-α induces an antiviral state that inhibits the replication of SAV-3 and protects the cells against virus-induced cytopathic effects (CPE). The antiviral state coincides with a strong expression of Mx and ISG15 mRNA and Mx protein expression. When rIFN-α is administered at the time of infection and up to 24 h postinfection, virus replication is not inhibited, and cells are not protected against virus-induced CPE. By 40 h postinfection, the alpha subunit of eukaryotic initiation factor 2 (eIF2α) is phosphorylated concomitant with the expression of the E2 protein as assessed by Western blotting. Postinfection treatment with rIFN-α results in a moderate reduction in E2 expression levels in accordance with a moderate downregulation of cellular protein synthesis, an approximately 65% reduction by 60 h postinfection. rIFN-γ has only a minor inhibitory effect on SAV-3 replication
in vitro
. SAV-3 is sensitive to the preinfection antiviral state induced by rIFN-α, while postinfection antiviral responses or postinfection treatment with rIFN-α is not able to limit viral replication.
Predictors of race-day jockey falls in flat racing in Australia
Authors: Hitchens Peta Lee , Blizzard Christopher Leigh , Jones Graeme , Day Lesley , Fell James
Published: June 2010

Objectives

Riding thoroughbred racehorses is a hazardous occupation. In this study, we investigated risk factors associated with falls by licensed thoroughbred racing jockeys participating in flat races conducted in Australia.

Methods

Data on race-day falls were extracted from stewards' reports. Denominator data were provided by Racing Information Services Australia on races conducted in Australia from August 2002 until July 2006. Incidence rate ratios (IRRs) were estimated using Poisson regression. Analyses were stratified by race grade (maiden, class, open/restricted).

Results

In multivariable analyses, factors associated with falls were female sex of jockey (IRR 1.11; 95% CI 1.00 to 1.23), being an apprentice jockey (IRR 1.51; 95% CI 1.39 to 1.63), being an amateur jockey (IRR 1.44; 95% CI 1.11 to 1.86), drier tracks (p<0.001), younger horse age (p<0.001), shorter race distance (p<0.001), lower field size (p=0.013) and lower race grade (p<0.001). The IRRs for five factors associated with falls differed by category of race grade: those for apprentice jockey (interaction p=0.003), higher prize money (interaction p<0.001) and shorter race distance (interaction p=0.041) were greater in lower race grades, while those for fewer previous rides this meeting (interaction p=0.027) and drier track rating (interaction p=0.035) were greater in higher race grades. Female jockeys had a significantly higher incidence of falls when riding horses under 4 years of age in open and restricted races (interaction p=0.038), and the effects of lower field size in maiden races, and of shorter races, were more pronounced for falls occurring before the race.

Conclusions

We identified a range of factors associated with falls to thoroughbred racing jockeys riding in flat races that adds to the evidence base for formulating strategies to improve occupational health and safety standards in the thoroughbred racing industry.
How valid is a short measure of effort–reward imbalance at work? A replication study from Sweden
Authors: Leineweber Constanze , Wege Natalia , Westerlund Hugo , Theorell Töres , Wahrendorf Morten , Siegrist Johannes
Published: June 2010

Objectives

There is an urgent need for validated measures of health-adverse psychosocial work environments. We tested the validity of a newly developed short version of the original questionnaire measuring effort–reward imbalance at work (ERI).

Methods

The study sample comprised working men and women (n=4771) participating in the Swedish Longitudinal Occupational Survey of Health (SLOSH), a nationally representative longitudinal cohort study, in 2006 and 2008. Structural equation modelling was applied to test factorial validity, using the ERI scales. Furthermore, criterion validity was explored with two prospectively assessed health indicators, poor self-reported health and depressive symptoms. Results are based on logistic and linear regression analyses, with appropriate confounder control.

Results

The short version of the ERI questionnaire (16 items) provides satisfactory psychometric properties (internal consistency of scales, confirmatory factor analysis with a good model fit of the data with the theoretical structure). All scales, and the effort–reward ratio, were prospectively associated with an increased risk of poor general self-rated health and depressive symptoms, indicating satisfactory criterion validity.

Conclusion

This short version of the ERI questionnaire provides a psychometrically useful tool for epidemiological studies focused on the health-adverse effects of work and employment in the context of a globalised economy.
Calculation of the benchmark duration of shift work associated with the development of impaired glucose metabolism: a 14-year cohort study on 7104 male workers
Authors: Suwazono Yasushi , Uetani Mirei , Oishi Mitsuhiro , Tanaka Kumihiko , Morimoto Hideki , Sakata Kouichi
Published: June 2010

Objectives

The aim of this study was to calculate the benchmark doses (BMD) and their 95% lower confidence boundary (BMDL) for the threshold number of years of shift work associated with a relative increase in haemoglobin A1c (HbA1c), an index of glucose metabolism.

Methods

A 14-year prospective cohort study was conducted in male workers at a Japanese steel company (n=7104) who had received annual health check-ups between 1991 and 2005. The endpoints were either a 10%, 15%, 20%, 25% or 30% increase in HbA1clevels during the observation period, compared to HbA1cat entry to the study. The associations between years of shift work and increases in HbA1cwere investigated using pooled logistic regression, adjusted for age, body mass index, mean arterial pressure, total serum cholesterol, creatinine, alanine aminotransferase, γ-glutamyl transpeptidase, uric acid, drinking habits, smoking habits and habitual exercise.

Results

The BMDL/BMD for years of shift work were calculated using benchmark responses (BMRs) of 5% or 10% and parameters for duration of shift work and other covariates. Assuming a mean age of 53 years in workers aged 50 years or older, the BMDL/BMD for years of shift work with a BMR of 5% were 17.8/23.9 (≥15%), 15.7/18.7 (≥20%), 18.9/22.7 (≥25%) and 25.2/31.7 (≥30%). With a BMR of 10%, the respective values were 29.5/39.7 (≥15%), 24.3/28.9 (≥20%), 27.3/32.7 (≥25%) and 34.1/42.9 (≥30%).

Conclusion

These results suggest that special attention should be paid to middle-aged workers whose years of shift work exceeds these threshold times.
HIGH-ENERGY EMISSION AND ABSORPTION IN CYGNUS X-1
Authors: DEL VALLE M. V. , ORELLANA M. , ROMERO G. E.
Published: June 2010

The high-mass microquasar Cygnus X-1 has been detected during a flaring state at very high energies, E > 200 GeV . The observation was performed by the Atmospheric Cherenkov Telescope MAGIC. It constitutes the first experimental evidence of very-high energy (VHE) emission produced by a Galactic stellar-mass black hole. The observed signal was detected in coincidence with an X–ray flare.

The gamma-ray flare occurred when the compact object was located behind the companion star with respect to the line of sight (superior conjunction of the compact object). In this configuration the absorption of VHE photons by annihilation with the stellar photons is expected to be maximum. This suggests that the emission has been originated far above the compact object. The energy spectrum is well fitted by a relatively soft power-law.

We present a model for the absorption and the emission of VHE gamma-rays in Cyg X-1. Detailed calculations of the gamma-ray opacity due to pair creation are provided and used to establish constraints on the emitting region. We propose that the high energy flare was the result of the interaction between the jet and a very dense clump from the stellar wind.
HIGH-ENERGY PARTICLE INTERACTIONS IN THE INNER JET OF THE RADIO GALAXY M87
Authors: GUENNOU CHLOÉ , ROMERO GUSTAVO E. , VILA GABRIELA S.
Published: June 2010

Recent observations with the High Energy Stereoscopic System (HESS) have revealed strong and variable high energy gamma-ray emission from the radio galaxy M87. The origin of such emission is uncertain, but the rapid variability indicates that it should be produced close to the central engine of the source. In this work, a lepto-hadronic one-zone model is applied to the available multiwavelength data of M87. The different energy losses for both primary and secondary particles are calculated. Then, the different contributions to the spectral energy distribution through interactions with matter, radiation and magnetic fields are obtained, in good accordance with the observations.
REVEALING THE NATURE OF NEW UNIDENTIFIED INTEGRAL SOURCES
Authors: MASETTI NICOLA , PARISI PIETRO , PALAZZI ELIANA , BASSANI LOREDANA , LANDI RAFFAELLA , MALIZIA ANGELA , SCHIAVONE FILOMENA , STEPHEN JOHN B. , JIMÉNEZ-BAILÓN ELENA , CHAVUSHYAN VAHRAM , MORELLI LORENZO , MASON ELENA , GALAZ GASPAR , MINNITI DANTE , BIRD ANTONY J. , DEAN ANTHONY J. , MCBRIDE VANESSA A. , CHARLES PHIL A. , BAZZANO ANGELA , UBERTINI PIETRO
Published: June 2010

Since its launch on October 2002, the INTEGRAL satellite has revolutionized our knowledge of the hard X–ray sky thanks to its unprecedented imaging capabilities and source detection positional accuracy above 20 keV. Nevertheless, many of the newly-detected sources in the INTEGRAL sky surveys are of unknown nature. However, the combined use of available information at longer wavelengths (mainly soft X–rays and radio) and of optical spectroscopy on the putative counterparts of these new hard X–ray objects allows pinpointing their exact nature. Continuing our long-standing program running since 2004 (and with which we identified more than 100 INTEGRAL objects) here we report the classification, through optical spectroscopy, of 25 unidentified high-energy sources, mostly belonging to the recently published 4-th IBIS survey.
THE OPTICAL AND NEAR-INFRARED COUNTERPART OF GRS 1758-258
Authors: MUÑOZ-ARJONILLA A. J. , MARTÍ J. , SÁNCHEZ-SUTIL J. R. , SÁNCHEZ-AYASO E. , LUQUE-ESCAMILLA P. L. , COMBI J. A. , MIRABEL I. F.
Published: June 2010

GRS 1758-258 is one of the two brightest persistent hard X–ray sources in the Galactic Center region, of which an optical/near infrared counterpart has not been unambiguously identified in previous work, mainly due to high absorption and the lack of suitable astrometric stars in early times. In this work, we take advantage of modern star catalogs to reanalyze archival images of the field in the optical and near infrared wavelengths, and compute a new astrometric solution. As a result, a single source is consistent with radio and X–ray sub-arcsec positions, which we propose as the counterpart of GRS 1758-258.
DISK–JET CONNECTION IN AGNs AND MICROQUASARS: THE POSSIBILITY OF THERMAL FLARES IN THE CENTER
Authors: TAMMI JONI , HOVATTA TALVIKKI
Published: June 2010

We discuss the possibility of thermal flares in centers of AGNs and microquasars. We present preliminary results of an ongoing study trying to assess the feasibility of a hypothesis suggesting that certain flares observed in these sources originate in the very centers of the systems and not in the relativistic jets. Using a simple toy model we reproduce optical flares with light curves very similar to those observed in the sources. The model suits especially well those cases where only the latter peak of a double-peaked optical flare has a radio counterpart.
QUIESCENT THERMAL EMISSION OF NEUTRON STARS IN LMXBs
Authors: TURLIONE ANABELA R. , PONS JOSE A. , AGUILERA DEBORAH N.
Published: June 2010

Recent monitoring of the quiescent thermal emission from NSs in low mass X–ray binaries (LMXBs) after active periods (bursts) opened a new view to the physics of dense matter. Theoretical modeling of the thermal relaxation of the crust may be used to establish constraints on the thermal conductivity of matter, depending on the accretion rate. We present here cooling curves obtained from numerical simulations that fit the light curves for two sources (KS 1731-260, MXB 1659-29). We estimate the model parameters (accretion rate, thermal conductivity) that match the data and compare our results with previous constraints of neutron star crust properties in LMXBs.
PULSE CHARACTERIZATION OF GRBs WITH KNOWN REDSHIFT
Authors: VASQUEZ NICOLAS , KAWAI NOBUYUKI
Published: June 2010

Gamma-ray Bursts (GRBs) are one of the most promising tools in the study of cosmology. The luminosity, energy, light curve parameters and spectral measures could yield to the calibration of standard candles in the Universe. Nevertheless, cosmological and non-cosmological effects are not well understood. Aiming to clarify the possible effects, we started to study the autocorrelation function (ACF) of a sample of GRBs with known redshift in the combined band of Swift (15–150 keV) and Suzaku (50 keV–5 Mev) satellites. We first confirmed the bimodal distribution of the cosmological corrected ACF reported by Borgonovo et al., then looking at the energy evolution we found a bimodal distribution of the decay index of the ACF. For the next step we explored the intrinsic effects of the pulses within GRBs, determining the ACF of individual pulses at two different energy bands, as well as the skewness of the pulse. We found two kinds of internal effects, the increase of the asymmetry of the pulse with energy and the variability-dependence on energy. Two types of pulses are distinguished, suggesting more than one physical process during the prompt emission.
NONTHERMAL RADIATION FROM CYGNUS X-1 CORONA
Authors: VIEYRO FLORENCIA L. , ROMERO GUSTAVO E. , VILA GABRIELA S.
Published: June 2010

Cygnus X-1 was the first X–ray source widely accepted to be a black hole candidate, and remains among the most studied astronomical objects in its class. The detection of nonthermal radio, hard X–rays and gamma-rays reveals the fact that this kind of objects are capable of accelerating particles up to very high energies.

In order to explain the electromagnetic emission from Cygnus X-1 in the low-hard state we present a model of a black hole corona with both relativistic lepton and hadron content. We characterize the corona as a two-temperature hot plasma plus a mixed nonthermal population in which energetic particles interact with magnetic, photon and matter fields. Our calculations include the radiation emitted by secondary particles (pions, muons and electron–positron pairs). Finally, we take into account the effects of photon absorption. We compare the results obtained from our model with data of Cygnus X-1 obtained by the COMPTEL instrument.
RELATIVISTIC JETS: OPEN PROBLEMS AND CHALLENGES
Authors: KÖNIGL ARIEH
Published: June 2010

Outstanding questions in the study of relativistic jets in their various astrophysical settings are discussed in the context of a general dynamical model.
RADIATIVE PROCESSES IN JETS
Authors: VILA GABRIELA S.
Published: June 2010

Relativistic jets and collimated outflows are ubiquitous phenomena in astrophysical settings, from young stellar objects up to Active Galactic Nuclei. The observed emission from some of these jets can cover the whole electromagnetic spectrum, from radio to gamma-rays. The relevant features of the spectral energy distributions depend on the nature of the source and on the characteristics of the surrounding environment. Here the author reviews the main physical processes that command the interactions between populations of relativistic particles locally accelerated in the jets, with matter, radiation and magnetic fields. Special attention is given to the conditions that lead to the dominance of the different radiative mechanisms. Examples from various types of sources are used to illustrate these effects.
STATIONARY SHEATH OF FARADAY ROTATION IN THE JET OF 3C 120
Authors: GÓMEZ JOSÉ L. , ROCA-SOGORB MAR , AGUDO IVÁN , MARSCHER ALAN P. , JORSTAD SVETLANA G.
Published: June 2010

We present a sequence of 12 monthly polarimetric multi-frequency VLBA observations of the radio galaxy 3C 120. The motion of multiple superluminal components allows the mapping of the polarization structure along most of the jet and across its width, revealing a coherent in time Faraday screen and RM-corrected polarization angles. Gradients in Faraday rotation and degree of polarization across the jet are observed, together with a localized region of high rotation measure superposed on this structure. This is explained as produced by the presence of a helical magnetic field in a two-fluid jet model, consisting of an inner emitting jet and a sheath containing nonrelativistic electrons. Interaction of the jet with the external medium would explain the confined region of enhanced Faraday rotation.
ELECTROMAGNETIC CASCADES IN MAGNETIZED MEDIA
Authors: PELLIZZA LEONARDO J. , ORELLANA MARIANA , ROMERO GUSTAVO E.
Published: June 2010

The investigation of the astrophysical nature of gamma-ray sources and the processes responsible for their broad-band emission requires a detailed modeling of their observable spectrum, in which electromagnetic cascades can play an important role. An open issue in this modeling is the effect of magnetic fields in the development of cascades. In this paper we present a novel numerical scheme to compute this effect in a self-consistent way. Applied to a toy model, our scheme reproduces the features expected for cascades in the strong and weak magnetic field regimes.
FROM DISK WINDS TO RELATIVISTIC JETS
Authors: PORTH OLIVER , FENDT CHRISTIAN
Published: June 2010

We investigate the relativistic acceleration and collimation of a wind launched from a magnetized accretion disk corona. Time-dependent simulations of the full set of special relativistic magnetohydrodynamic (RMHD) equations are performed with the publicly available PLUTO1 code. In order to provide an injection boundary in dynamical equilibrium, Newtoninan gravity was added as a source term. The flow starts out with sub-escape velocity and we allow for sub-magnetoslow injection to consistently prescribe the mass-loading. The detailed trans-field and parallel-field force-balances are shown with highlights on the relativistic contribution due to electric fields.2 Generally we find collimated flows with mass-weighted half-opening angles of 3–7 degrees and mildly relativistic velocities. The outer subrelativistic flow is a promising candidate for the X–ray absorption winds that are observed in many radio-quiet active galactic nulei (AGN).
JETS ON ALL SCALES
Authors: LEVINSON AMIR
Published: June 2010

A brief overview of jets and their central drivers is presented, with a focus on accreting black hole systems. In particular, scaling relations that elucidate some basic properties of the engines are derived, and the implications for the associated outflows are discussed. The kinematics and dynamics of relativistic jets in various systems and the dissipation of their bulk energy is considered, with an emphasis on consequences of recent observations. Also considered is the interaction of the jets with their environment. Comments on multi-messenger probes are made at the end.
SECONDARY EMISSION BEHIND THE RADIO OUTFLOWS IN GAMMA-RAY BINARIES
Authors: BOSCH-RAMON VALENTÍ
Published: June 2010

Several binary systems consisting of a massive star and a compact object have been detected above 100 GeV in the Galaxy. In most of these sources, gamma-rays show a modulation associated to the orbital motion, which means that the emitter should not be too far from the bright primary star. This implies that gamma-ray absorption will be non-negligible, and large amounts of secondary electron–positron pairs will be created in the stellar surroundings. In this work, we show that the radio emission from these pairs should be accounted for when interpreting the radio spectrum, variability, and morphology found in gamma-ray binaries. Relevant features of the secondary radio emission are the relatively hard spectrum, the orbital motion of the radio peak center and the radio structure extension following a spiral-like trajectory. The impact of the stellar wind free–free absorption should not be neglected.
MODELING INTERMEDIATE BL LAC OBJECTS DETECTED BY VERITAS
Authors: BÖTTCHER MARKUS
Published: June 2010

Modeling implications of recent VERITAS discoveries of Intermediate BL Lac Objects (IBLs) are presented. Leptonic jet models for the IBLs W Comae (z = 0.102) and 3C 66A (z = 0.444) are, in principle, viable with only synchrotron and synchrotron self-Compton (SSC) components, but more plausible parameters can be achieved including an external infrared radiation field as source for Compton upscattering to produce the observed VHE gamma-ray emission. The unknown redshift of PKS 1424+240 makes a theoretical interpretation difficult. A pure SSC model seems to be sufficient to represent its SED, and modeling results favor a low redshift of z ≲ 0.1.
Cardiac contractile dysfunction during acute hyperglycemia due to impairment of SERCA by polyol pathway-mediated oxidative stress
Authors: Tang Wai Ho , Cheng Wing Tim , Kravtsov Gennadi M. , Tong Xiao Yong , Hou Xiu Yun , Chung Sookja K. , Chung Stephen Sum Man
Published: June 2010

Hyperglycemia is an indication of poor outcome for heart attack patients, even for nondiabetic patients with stress-induced hyperglycemia. Previous studies showed that inhibition of aldose reductase, the first and rate-limiting enzyme of the polyol pathway, attenuated contractile dysfunction in diabetic animals, but the mechanism is unclear. We therefore wanted to find out whether the polyol pathway also contributes to acute hyperglycemia-induced cardiac contractile dysfunction, and determine the mechanism involved. Rat hearts were isolated and retrogradely perfused with Krebs buffer containing either normal or high concentrations of glucose for 2 h. Short exposure to high-glucose medium led to contractile dysfunction as indicated by decreased −dP/d tmax, as well as elevation in left ventricular end-diastolic pressure. Cardiomyocytes incubated in high-glucose medium showed abnormal Ca2+ signaling, most likely because of decreased activity of sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) inactivated by oxidative stress. Inhibition of aldose reductase or sorbitol dehydrogenase, the second enzyme in the polyol pathway, ameliorated contractile dysfunction, attenuated oxidative stress, and normalized Ca2+ signaling and SERCA activity caused by high glucose, indicating that the polyol pathway is the major contributor to acute hyperglycemia-induced oxidative stress leading to the inactivation of SERCA and contractile dysfunction.
Transferrin receptor 2 is crucial for iron sensing in human hepatocytes
Authors: Rapisarda Chiara , Puppi Juliana , Hughes Robin D. , Dhawan Anil , Farnaud Sebastien , Evans Robert W. , Sharp Paul A.
Published: June 2010

Hepcidin expression in vivo is regulated in proportion to iron status (i.e., increased by iron loading and decreased in iron deficiency). However, in vitro studies with hepatoma cell lines often show an inverse relationship between iron status and hepcidin expression. Here, we investigated possible molecular mechanisms responsible for the differences in iron sensing between hepatoma cell lines and human primary hepatocytes. RNA was collected from primary human hepatocytes, and HepG2 and HuH7 hepatoma cells were treated with either transferrin-bound and non-transferrin-bound iron. Expression of hepcidin, transferrin receptor 2, HFE, and hemojuvelin were quantified by real-time PCR. Hepcidin expression was increased in primary human hepatocytes following 24-h exposure to holoferric transferrin. In contrast, hepcidin mRNA levels in hepatoma cells were decreased by transferrin. Hepcidin expression was positively correlated with transferrin receptor 2 mRNA levels in primary human hepatocytes. Compared with primary hepatocytes, transferrin receptor 2 expression was significantly lower in hepatoma cell lines; furthermore, there was no correlation between transferrin receptor 2 and hepcidin mRNA levels in either HepG2 or HuH7 cells. Taken together our data suggest that transferrin receptor 2 is a likely candidate to explain the differences in iron sensing between hepatoma cell lines and primary human hepatocytes.
External Urethral Sphincter Motoneuron Properties in Adult Female Rats Studied In Vitro
Authors: Carp Jonathan S. , Tennissen Ann M. , Liebschutz Jennifer E. , Chen Xiang Yang , Wolpaw Jonathan R.
Published: June 2010

The external urethral sphincter (EUS) muscle plays a crucial role in lower urinary tract function: its activation helps maintain continence, whereas its relaxation contributes to micturition. To determine how the intrinsic properties of its motoneurons contribute to its physiological function, we have obtained intracellular current-clamp recordings from 49 EUS motoneurons in acutely isolated spinal cord slices from adult female rats. In all, 45% of EUS motoneurons fired spontaneously and steadily (average rate = 12–27 pulses/s). EUS motoneurons were highly excitable, having lower rheobase, higher input resistance, and smaller threshold depolarization than those of rat hindlimb motoneurons recorded in vitro. Correlations between these properties and afterhyperpolarization half-decay time are consistent with EUS motoneurons having characteristics of both fast and slow motor unit types. EUS motoneurons with a slow-like spectrum of properties exhibited spontaneous firing more often than those with fast-like characteristics. During triangular current ramp-induced repetitive firing, recruitment typically occurred at lower current levels than those at derecruitment, although the opposite pattern occurred in 10% of EUS motoneurons. This percentage was likely underestimated due to firing rate adaptation. These findings are consistent with the presence of a basal level of persistent inward current (PIC) in at least some EUS motoneurons. The low EUS motoneuron current and voltage thresholds make them readily recruitable, rendering them well suited to their physiological role in continence. The expression of firing behaviors consistent with PIC activation in this highly reduced preparation raises the possibility that in the intact animal, PICs contribute to urinary function not only through neuromodulator-dependent but also through neuromodulator-independent mechanisms.
Dissociating Bottom-Up and Top-Down Processes in a Manual Stimulus–Response Compatibility Task
Authors: Cieslik Edna C. , Zilles Karl , Kurth Florian , Eickhoff Simon B.
Published: June 2010

Speed and accuracy of motor responses to lateralized stimuli are influenced by the spatial overlap between stimulus location and required response. Responses showing high spatial overlap with peripheral cues benefit from a bottom-up driven enhancement of attention to the respective location, whereas low overlap requires top-down modulated reorienting of resources. Here we investigated the interaction between these two processes using a spatial stimulus-response compatibility task. Subjects had to react to lateralized visual stimuli with a button press using either the ipsilateral (congruent condition) or the contralateral (incongruent condition) index finger. Stimulus-driven bottom-up processes were associated with significant contralateral activation in V5, the intraparietal sulcus (IPS) and the premotor cortex (PMC). Incongruent versus congruent responses evoked significant activation in bilateral IPS and PMC, highly overlapping with the activations found for stimulus-driven bottom-up processes, as well as additional activation in bilateral anterior insula and right dorsolateral prefrontal cortex (DLPFC) and temporoparietal junction (TPJ). Moreover, a region anterior to the bottom-up driven activation in the IPS was associated with top-down modulated directionality-specific reorienting of motor attention during incongruent motor responses. Based on these results, we propose that stimulus-driven activation of contralateral IPS and PMC represent key neuronal substrates for the behavioral advantage observed when reacting toward a congruently lateralized stimulus. Additional activation in bilateral insula and right DLPFC and TPJ during incongruent responses should reflect top-down control mechanisms mediating contextual (i.e., task) demands. Furthermore, this study provides evidence for both overlapping and disparate substrates of bottom-up and top-down modulated attentional processes in the IPS.
Feedback and Feedforward Locomotor Adaptations to Ankle-Foot Load in People With Incomplete Spinal Cord Injury
Authors: Gordon Keith E. , Wu Ming , Kahn Jennifer H. , Schmit Brian D.
Published: June 2010

Humans with spinal cord injury (SCI) modulate locomotor output in response to limb load. Understanding the neural control mechanisms responsible for locomotor adaptation could provide a framework for selecting effective interventions. We quantified feedback and feedforward locomotor adaptations to limb load modulations in people with incomplete SCI. While subjects airstepped (stepping performed with kinematic assistance and 100% bodyweight support), a powered-orthosis created a dorisflexor torque during the “stance phase” of select steps producing highly controlled ankle-load perturbations. When given repetitive, stance phase ankle-load, the increase in hip extension work, 0.27 J/kg above baseline (no ankle-load airstepping), was greater than the response to ankle-load applied during a single step, 0.14 J/kg ( P = 0.029). This finding suggests that, at the hip, subjects produced both feedforward and feedback locomotor modulations. We estimate that, at the hip, the locomotor response to repetitive ankle-load was modulated almost equally by ongoing feedback and feedforward adaptations. The majority of subjects also showed after-effects in hip kinetic patterns that lasted 3 min in response to repetitive loading, providing additional evidence of feedforward locomotor adaptations. The magnitude of the after-effect was proportional to the response to repetitive ankle-foot load ( R2= 0.92). In contrast, increases in soleus EMG amplitude were not different during repetitive and single-step ankle-load exposure, suggesting that ankle locomotor modulations were predominately feedback-based. Although subjects made both feedback and feedforward locomotor adaptations to changes in ankle-load, between-subject variations suggest that walking function may be related to the ability to make feedforward adaptations.
Desmosomes In Vivo
Authors: Garrod David
Published: June 2010

The structure, function, and regulation of desmosomal adhesion in vivo are discussed. Most desmosomes in tissues exhibit calcium‐independent adhesion, which is strongly adhesive or “hyperadhesive”. This is fundamental to tissue strength. Almost all studies in culture are done on weakly adhesive, calcium‐dependent desmosomes, although hyperadhesion can be readily obtained in confluent cell culture. Calcium dependence is a default condition in vivo, found in wounds and embryonic development. Hyperadhesion appears to be associated with an ordered arrangement of the extracellular domains of the desmosomal cadherins, which gives rise to the intercellular midline identified in ultrastructural studies. This in turn probably depends on molecular order in the desmosomal plaque. Protein kinase C downregulates hyperadhesion and there is preliminary evidence that it may also be regulated by tyrosine kinases. Downregulation of desmosomes in vivo may occur by internalisation of whole desmosomes rather than disassembly. Hyperadhesion has implications for diseases such as pemphigus.
Alveolar Osteitis: A Comprehensive Review of Concepts and Controversies
Authors: Kolokythas Antonia , Olech Eliza , Miloro Michael
Published: June 2010

Alveolar osteitis, “dry socket”, remains amongst the most commonly encountered complications following extraction of teeth by general dentists and specialists. A great body of literature is devoted to alveolar osteitis addressing the etiology and pathophysiology of this condition. In addition numerous studies are available discussing methods and techniques to prevent this condition. To this date though great controversy still exists regarding the appropriate terminology used for this condition as well as the actual etiology, pathophysiology, and best methods of prevention and treatment. This article is a comprehensive critical review of the available literature addressing the concepts and controversies surrounding alveolar osteitis. We aim to assist the dental health care professional with patient preparation and management of this commonly encountered postoperative condition should be encountered.
Physical Activity in Adolescent Females with Type 1 Diabetes
Authors: Schweiger Bahareh , Klingensmith Georgeanna , Snell-Bergeon Janet K.
Published: June 2010

Objective. We sought to identify amount of physical activity and relationship of physical activity to glycemic control among adolescent females 11 to 19 years of age with type 1 diabetes mellitus (T1DM). We also sought to evaluate associations of age and ethnicity with physical activity levels.Research Design and Methods. Adolescent females ages 11–19 years (n=203) were recruited during their outpatient diabetes appointment. Physical activity was obtained by self-report and was categorized as the number of days subjects had accumulated 60 minutes of moderate-to-vigorous physical activity during the past 7 days and for a typical week.Results. Girls reported being physically active for at least 60 minutes per day on2.7±2.3days in the last week, and on3.1±2.2days in a typical week. A greater number of physically active days in a typical week were associated with lower A1c (P=.049) in linear regression analysis.Conclusion. Adolescent females with T1DM report exercising for at least 60 minutes about 3 days per week, which does not meet the international recommendations of 60 minutes of moderate-to-vigorous activity per day. It is particularly important that adolescent girls with T1DM be encouraged to exercise since a greater number of physically active days per week is associated with better glycemic control.
Use ofNNatural Abundance and N Species Concentrations to Assess N-Cycling in Constructed and Natural Coastal Wetlands
Authors: Aelion C. Marjorie , Engle Melissa R. , Ma Hongbo
Published: June 2010

Natural abundance of N stable isotopes used in combination with concentrations may be useful indicators of N-cycling in wetlands. Concentrations andNsignatures ofNO3−,NH4+, and sediment organic nitrogen (SON) were measured in two impacted coastal golf course retention ponds and two natural marshes. LimitedNO3−was detected in natural site surface water or pore water, but both isotopic signature and concentrations ofNO3−in surface water of impacted sites indicated anthropogenic inputs. In natural sites,NH4+concentrations were greatest in deeper pore water and least in surface water, suggesting diffusion predominates. The natural sites had greater %SON, andNindicated that the natural sites also had greaterNH4+released from SON mineralization than impacted sites. InNO3−-limited systems, neither concentrations norNnatural abundance was able to provide information on N-cycling, while processes associated withNH4+were better elucidated by using both concentrations andNnatural abundance.
Hsp90 as a Gatekeeper of Tumor Angiogenesis: Clinical Promise and Potential Pitfalls
Authors: Bohonowych J. E. , Gopal U. , Isaacs J. S.
Published: June 2010

Tumor vascularization is an essential modulator of early tumor growth, progression, and therapeutic outcome. Although antiangiogenic treatments appear promising, intrinsic and acquired tumor resistance contributes to treatment failure. Clinical inhibition of the molecular chaperone heat shock protein 90 (Hsp90) provides an opportunity to target multiple aspects of this signaling resiliency, which may elicit more robust and enduring tumor repression relative to effects elicited by specifically targeted agents. This review highlights several primary effectors of angiogenesis modulated by Hsp90 and describes the clinical challenges posed by the redundant circuitry of these pathways. The four main topics addressed include (1) Hsp90-mediated regulation of HIF/VEGF signaling, (2) chaperone-dependent regulation of HIF-independent VEGF-mediated angiogenesis, (3) Hsp90-dependent targeting of key proangiogenic receptor tyrosine kinases and modulation of drug resistance, and (4) consideration of factors such as tumor microenvironment that pose several challenges for the clinical efficacy of anti-angiogenic therapy and Hsp90-targeted strategies.
A Review of Gait Optimization Based on Evolutionary Computation
Authors: Gong Daoxiong , Yan Jie , Zuo Guoyu
Published: June 2010

Gait generation is very important as it directly affects the quality of locomotion of legged robots. As this is an optimization problem with constraints, it readily lends itself to Evolutionary Computation methods and solutions. This paper reviews the techniques used in evolution-based gait optimization, including why Evolutionary Computation techniques should be used, how fitness functions should be composed, and the selection of genetic operators and control parameters. This paper also addresses further possible improvements in the efficiency and quality of evolutionary gait optimization, some problems that have not yet been resolved and the perspectives for related future research.
Viscoelastic Fluid over a Stretching Sheet with Electromagnetic Effects and Nonuniform Heat Source/Sink
Authors: Hsiao Kai-Long
Published: June 2010

A magnetic hydrodynamic (MHD) of an incompressible viscoelastic fluid over a stretching sheet with electric and magnetic dissipation and nonuniform heat source/sink has been studied. The buoyant effect and the electric number E1 couple with magnetic parameter M to represent the dominance of the electric and magnetic effects, and adding the specific item of nonuniform heat source/sink is presented in governing equations which are the main contribution of this study. The similarity transformation, the finite‐difference method, Newton method, and Gauss elimination method have been used to analyze the present problem. The numerical solutions of the flow velocity distributions, temperature profiles, and the important wall unknown values of f′′(0) and θ′(0) have been carried out. The parameter Pr, E1, or Ec can increase the heat transfer effects, but the parameter M or A* may decrease the heat transfer effects.
The Effects of Red and Blue Lights on Circadian Variations in Cortisol, Alpha Amylase, and Melatonin
Authors: Figueiro Mariana G. , Rea Mark S.
Published: June 2010

The primary purpose of the present study was to expand our understanding of the impact of light exposures on the endocrine and autonomic systems as measured by acute cortisol, alpha amylase, and melatonin responses. We utilized exposures from narrowband long-wavelength (red) and from narrow-band short-wavelength (blue) lights to more precisely understand the role of the suprachiasmatic nuclei (SCN) in these responses. In a within-subjects experimental design, twelve subjects periodically received one-hour corneal exposures of 40 lux from the blue or from the red lights while continuously awake for 27 hours. Results showed-that, as expected, only the blue light reduced nocturnal melatonin. In contrast, both blue and red lights affected cortisol levels and, although less clear, alpha amylase levels as well. The present data bring into question whether the nonvisual pathway mediating nocturnal melatonin suppression is the same as that mediating other responses to light exhibited by the endocrine and the autonomic nervous systems.