Recombinant Flag-tagged E1E2 glycoproteins from three hepatitis C virus genotypes are biologically functional and elicit cross-reactive neutralizing antibodies in mice

Hepatitis C virus (HCV) is a globally disseminated human pathogen for which no vaccine is currently available. HCV is highly diverse genetically and can be classified into 7 genotypes and multiple sub-types. Due to this antigenic variation, the induction of cross-reactive and at the same time neutralizing antibodies is a challenge in vaccine production. Here we report the analysis of immunogenicity of recombinant HCV envelope glycoproteins from genotypes 1a, 1b and 2a, with a Flag tag inserted in the hypervariable region 1 of E2. This modification did not affect protein expression or conformation or its capacity to bind the crucial virus entry factor, CD81. Importantly, in immunogenicity studies on mice, the purified E2-Flag mutants elicited high-titer, cross-reactive antibodies that were able to neutralize HCV infectious particles from two genotypes tested (1a and 2a). These findings indicate that E1E2-Flag envelope glycoproteins could be important immunogen candidates for vaccine aiming to induce broad HCV-neutralizing responses

The selling of put derivatives by firms for shareholder wealth and information signaling enhancement

Working paper; version dated November 5, 200

Dust Emission from Evolved and Unevolved HII Regions in the Large Magellanic Cloud

We present a study of the dust properties of 12 classical and superbubble HII regions in the Large Magellanic Cloud. We use infrared photometry from Spitzer (8, 24, 70, and 160 \mum bands), obtained as part of the Surveying the Agents of a Galaxy's Evolution (SAGE) program, along with archival spectroscopic classifications of the ionizing stars to examine the role of stellar sources on dust heating and processing. Our infrared observations show surprisingly little correlation between the emission properties of the dust and the effective temperatures or bolometric magnitudes of stars in the HII regions, suggesting that the HII region evolutionary timescale is not on the order of the dust processing timescale. We find that the infrared emission of superbubbles and classical HII regions shows little differentiation between the two classes, despite the significant differences in age and morphology. We do detect a correlation of the 24 \mum emission from hot dust with the ratio of 70 to 160 \mum flux. This correlation can be modeled as a trend in the temperature of a minority hot dust component, while a majority of the dust remains significantly cooler.Comment: 15 pages, 5 figures. Accepted to Ap

OGLE-2003-BLG-262: Finite-Source Effects from a Point-Mass Lens

We analyze OGLE-2003-BLG-262, a relatively short, t_E=12.5+-0.1day, microlensing event generated by a point-mass lens transiting the face of a K giant source in the Galactic bulge. We use the resulting finite-source effects to measure the angular Einstein radius, theta_E=195+-17muas, and so constrain the lens mass to the full-width half-maximum interval 0.08 < M/M_sun < 0.54. The lens-source relative proper motion is mu_rel = 27+-2 km/s/kpc. Both values are typical of what is expected for lenses detected toward the bulge. Despite the short duration of the event, we detect marginal evidence for a "parallax asymmetry", but argue that this is more likely to be induced by acceleration of the source, a binary lens, or possibly by statistical fluctuations. Although OGLE-2003-BLG-262 is only the second published event to date in which the lens transits the source, such events will become more common with the new OGLE-III survey in place. We therefore give a detailed account of the analysis of this event to facilitate the study of future events of this type.Comment: 9 pages, 6 figures, accepted for publication in the Astrophysical Journa

Microlensing optical depth toward the Galactic Bulge using bright sources from OGLE-II

We present a measurement of the microlensing optical depth toward the Galactic Bulge based on 4 years of the OGLE-II survey using Red Clump Giant (RCG). Using 32 events we find tau=2.55_{-0.46}^{+0.57}* 10^{-6} at (l,b)=(1.16, -2.75). Taking into account the measured gradient along the Galactic latitude b, tau = [ (4.48+/- 2.37) + (0.78+/- 0.84)* b]* 10^{-6}, this value is consistent with previous measurements using RCG sources and recent theoretical predictions. We determine the microlensing parameters and select events using a model light curve with the flux blending. We find that ~38% of the OGLE-II events which appear to have RCG sources are actually due to much fainter stars blended with a bright companion. We show explicitly that model fits without blending result in similar tau estimates through partial cancellation of contributions from higher detection efficiency, underestimated time-scales and larger number of selected events. This approach, however, leads to biased time-scale distributions and event rates. Consequently, microlensing studies should carefully consider source confusion effects even for bright stars.Comment: 49 pages and 18 figures, ApJ in press, the value changed due to the systematic correctio

Planetary Detection Efficiency of the Magnification 3000 Microlensing Event OGLE-2004-BLG-343

OGLE-2004-BLG-343 was a microlensing event with peak magnification A_{max}=3000+/-1100, by far the highest-magnification event ever analyzed and hence potentially extremely sensitive to planets orbiting the lens star. Due to human error, intensive monitoring did not begin until 43 minutes after peak, at which point the magnification had fallen to A~1200, still by far the highest ever observed. As the light curve does not show significant deviations due to a planet, we place upper limits on the presence of such planets by extending the method of Yoo et al. (2004b), which combines light-curve analysis with priors from a Galactic model of the source and lens populations, to take account of finite-source effects. This is the first event so analyzed for which finite-source effects are important, and hence we develop two new techniques for evaluating these effects. Somewhat surprisingly, we find that OGLE-2004-BLG-343 is no more sensitive to planets than two previously analyzed events with A_{max}~100, despite the fact that it was observed at ~12 times higher magnification. However, we show that had the event been observed over its peak, it would have been sensitive to almost all Neptune-mass planets over a factor of 5 of projected separation and even would have had some sensitivity to Earth-mass planets. This shows that some microlensing events being detected in current experiments are sensitive to very low-mass planets. We also give suggestions on how extremely high-magnification events can be more promptly monitored in the future.Comment: 50 pages, 13 figures, published in The Astrophysical Journa

Functional Regeneration of Supraspinal Connections in a Patient With Transected Spinal Cord Following Transplantation of Bulbar Olfactory Ensheathing Cells With Peripheral Nerve Bridging

Treatment of patients sustaining a complete spinal cord injury remains an unsolved clinical problem because of the lack of spontaneous regeneration of injured central axons. A 38-year-old man sustained traumatic transection of the thoracic spinal cord at upper vertebral level Th9. At 21 months after injury, the patient presented symptoms of a clinically complete spinal cord injury (American Spinal Injury Association class A-ASIA A). One of the patient's olfactory bulbs was removed and used to derive a culture containing olfactory ensheathing cells and olfactory nerve fibroblasts. Following resection of the glial scar, the cultured cells were transplanted into the spinal cord stumps above and below the injury and the 8-mm gap bridged by four strips of autologous sural nerve. The patient underwent an intense pre- and postoperative neurorehabilitation program. No adverse effects were seen at 19 months postoperatively, and unexpectedly, the removal of the olfactory bulb did not lead to persistent unilateral anosmia. The patient improved from ASIA A to ASIA C. There was improved trunk stability, partial recovery of the voluntary movements of the lower extremities, and an increase of the muscle mass in the left thigh, as well as partial recovery of superficial and deep sensation. There was also some indication of improved visceral sensation and improved vascular autoregulation in the left lower limb. The pattern of recovery suggests functional regeneration of both efferent and afferent long-distance fibers. Imaging confirmed that the grafts had bridged the left side of the spinal cord, where the majority of the nerve grafts were implanted, and neurophysiological examinations confirmed the restitution of the integrity of the corticospinal tracts and the voluntary character of recorded muscle contractions. To our knowledge, this is the first clinical indication of the beneficial effects of transplanted autologous bulbar cells

Relative distances of Omega Centauri and 47 Tucanae

We present precise optical and near-infrared ground-based photometry of two Globular Clusters (GCs): Omega Cen and 47 Tuc. These photometric catalogs are unbiased in the Red Giant Branch (RGB) region close to the tip. We provide new estimates of the RGB tip (TRGB) magnitudes--m_I(TRGB)=9.84+/-0.05, Omega Cen; m_I(TRGB)=9.46+/-0.06, 47 Tuc--and use these to determine the relative distances of the two GCs. We find that distance ratios based on different calibrations of the TRGB, the RR Lyrae stars and kinematic distances agree with each other within one sigma. Absolute TRGB and RR Lyrae distance moduli agree within 0.10--0.15 mag, while absolute kinematic distance moduli are 0.2--0.3 mag smaller. Absolute distances to 47 Tuc based on the Zero-Age-Horizontal-Branch and on the white dwarf fitting agree within 0.1 mag, but they are 0.1--0.3 mag smaller than TRGB and RR Lyrae distances.Comment: 5 pages, 4 figures, accepted for publication by ApJ

Constraints on Planetary Companions in the Magnification A=256 Microlensing Event: OGLE-2003-BLG-423

We develop a new method of modeling microlensing events based on a Monte Carlo simulation that incorporates both a Galactic model and the constraints imposed by the observed characteristics of the event. The method provides an unbiased way to analyze the event especially when parameters are poorly constrained by the observed lightcurve. We apply this method to search for planetary companions of the lens in OGLE-2003-BLG-423, whose maximum magnification A_max=256+-43 (or A_max=400+-115 from the lightcurve data alone) is the highest among single-lens events ever recorded. The method permits us, for the first time, to place constraints directly in the planet-mass/projected-physical-separation plane rather than in the mass-ratio/Einstein-radius plane as was done previously. For example, Jupiter-mass companions of main-sequence stars at 2.5 AU are excluded with 80% efficiency.Comment: 10 pages, 7 figures, accepted for publication in The Astrophysical Journa