Evolving outer heliosphere: Large-scale stability and time variations observed by the Interstellar Boundary Explorer

The first all-sky maps of Energetic Neutral Atoms (ENAs) from the Interstellar Boundary Explorer (IBEX) exhibited smoothly varying, globally distributed flux and a narrow ribbon of enhanced ENA emissions. In this study we compare the second set of sky maps to the first in order to assess the possibility of temporal changes over the 6 months between views of each portion of the sky. While the large-scale structure is generally stable between the two sets of maps, there are some remarkable changes that show that the heliosphere is also evolving over this short timescale. In particular, we find that (1) the overall ENA emissions coming from the outer heliosphere appear to be slightly lower in the second set of maps compared to the first, (2) both the north and south poles have significantly lower (similar to 10-15%) ENA emissions in the second set of maps compared to the first across the energy range from 0.5 to 6 keV, and (3) the knot in the northern portion of the ribbon in the first maps is less bright and appears to have spread and/or dissipated by the time the second set was acquired. Finally, the spatial distribution of fluxes in the southernmost portion of the ribbon has evolved slightly, perhaps moving as much as 6 degrees (one map pixel) equatorward on average. The observed large-scale stability and these systematic changes at smaller spatial scales provide important new information about the outer heliosphere and its global interaction with the galaxy and help inform possible mechanisms for producing the IBEX ribbon

Eukaryotic initiation factor-4E in superficial and muscle invasive bladder cancer and its correlation with vascular endothelial growth factor expression and tumour progression

Vascular endothelial growth factor (VEGF) is an important factor mediating tumour angiogenesis. VEGF mRNA is differentially expressed in bladder cancer with high expression in superficial tumours (stage pTaand pT1) contrasting with low expression in muscle invasive tumours (stage ≥ pT2). To investigate mechanisms regulating VEGF expression in bladder cancer, VEGF mRNA and protein were measured in normal bladder (n = 12) and primary bladder cancers (n = 57). VEGF protein levels correlated with mRNA expression in normal bladder (r = 0.68, P = 0.02) and bladder cancer (r = 0.46, P = 0.0007). Whilst VEGF mRNA expression was threefold higher in superficial compared to muscle invasive bladder cancers (P = 0.0001) there was no difference in VEGF protein (P = 0.81). Accordingly, the median protein:mRNA ratios increased more than 15-fold with increasing tumour stage (P< 0.0001) suggesting translational regulation. Expression of the eukaryotic initiation factor-4E (eIF-4E), a factor implicated in the translational regulation of VEGF, was greater in tumours than normal bladder (P< 0.0001) and correlated with VEGF protein:mRNA ratios (n = 43, r = 0.54, P = 0.0004) pointing to its role in the regulation of VEGF. In superficial tumours (n = 37) high expression of eIF-4E was associated with a poor prognosis and reduced stage progression-free survival (P = 0.04, Cox proportional hazards model). The study demonstrates that eIF-4E may be involved in translational regulation of VEGF in bladder cancer and might have a role as a prognostic factor in bladder cancer. © 2000 Cancer Research Campaig

The hypoxia-inducible genes VEGF and CA9 are differentially regulated in superficial vs invasive bladder cancer

Regulation by hypoxia may underlie the expression of vascular endothelial growth factor in bladder cancer. We have compared the distribution of vascular endothelial growth factor mRNA with a hypoxia marker, carbonic anhydrase 9 (CA IX). vascular endothelial growth factor mRNA was analysed by in situ hybridisation and CA IX by immunochemistry in 22 cases of bladder cancer. The relationship of microvessels to the distribution of CA IX was determined. In a separate series of 49 superficial tumours, CA IX immunostaining was compared with clinico-pathological outcome. In superficial and invasive disease there was overlap in the expression of vascular endothelial growth factor and CA IX, CA IX being more widespread. Both were expressed predominantly on the luminal surface, and surrounding areas of necrosis (invasive tumours). Expression of both factors was greater in superficial disease. Expression was absent within ∼80 μm of microvessels. Unlike vascular endothelial growth factor, CA IX did not predict outcome in superficial disease. Differential responses to reoxygenation provide one explanation: vascular endothelial growth factor mRNA declined rapidly, while CA IX expression was sustained for >72 h. Expression of vascular endothelial growth factor mRNA in bladder tumours is consistent with hypoxic regulation and suggests differential regulation in superficial vs invasive disease. The expression of CA IX on the luminal surface justifies investigation of its utility as a therapeutic target/prognostic indicator

Neutral interstellar helium parameters based on IBEX-Lo observations and test particle calculations

Neutral Interstellar Helium (NISHe) is almost unaffected at the heliospheric interface with the interstellar medium and freely enters the solar system. It provides some of the best information on the characteristics of the interstellar gas in the Local Interstellar Cloud. The Interstellar Boundary Explorer (IBEX) is the second mission to directly detect NISHe. We present a comparison between recent IBEX NISHe observations and simulations carried out using a well-tested quantitative simulation code. Simulation and observation results compare well for times when measured fluxes are dominated by NISHe (and contributions from other species are small). Differences between simulations and observations indicate a previously undetected secondary population of neutral helium, likely produced by interaction of interstellar helium with plasma in the outer heliosheath. Interstellar neutral parameters are statistically different from previous in situ results obtained mostly from the GAS/Ulysses experiment, but they do agree with the local interstellar flow vector obtained from studies of interstellar absorption: the newly-established flow direction is ecliptic longitude 79.2 deg, latitude -5.1 deg, the velocity is \sim 22.8 km/s, and the temperature is 6200 K. These new results imply a markedly lower absolute velocity of the gas and thus significantly lower dynamic pressure on the boundaries of the heliosphere and different orientation of the Hydrogen Deflection Plane compared to prior results from Ulysses. A different orientation of this plane also suggests a new geometry of the interstellar magnetic field and the lower dynamic pressure calls for a compensation by other components of the pressure balance, most likely a higher density of interstellar plasma and strength of interstellar magnetic field.Comment: Data from IBEX-Lo on Interstellar Boundary Explorer analyzed; 40 pages, 24 figures, 2 table

Phase I trial of intravesical Suramin in recurrent superficial transitional cell bladder carcinoma

Suramin is an antitrypanosomal agent with antineoplastic activity, but with serious systemic side effects. We administered Suramin intravesically to determine a concentration with low toxicity but with evidence of a pharmacodynamic effect, to recommend a dose level for phase II trials. This was an open-labelled, nonrandomised dose-escalation phase I study. In all, 12 patients with a history of recurrent superficial bladder cancer were grouped into four dose levels (10–150 mg ml−1 in 60 ml saline). Six catheter instillations at weekly intervals were used. Cystoscopy and biopsy were performed before and 3 months after the start of treatment. Suramin was assayed using high-performance liquid chromatography, vascular endothelial growth factor (VEGF) using ELISA (enzyme-linked immunosorbent assay), and urinary protein profile using surface-enhanced laser desorption ionisation mass spectroscopy (SELDI). Minimal systemic absorption of Suramin was found at the highest dose of 150 mg ml−1. Urinary VEGF was affected by Suramin at doses above 50 mg ml−1, corresponding to the estimated threshold of saturation of Suramin binding to urine albumin. SELDI showed a specific disappearance of urinary protein peaks during treatment. Intravesical Suramin shows lack of toxicity and low systemic absorption. The results of this phase I trial support expanded clinical trials of efficacy at a dose of 100 mg ml−1 intravesically

First 230 GHz VLBI Fringes on 3C 279 using the APEX Telescope

We report about a 230 GHz very long baseline interferometry (VLBI) fringe finder observation of blazar 3C 279 with the APEX telescope in Chile, the phased submillimeter array (SMA), and the SMT of the Arizona Radio Observatory (ARO). We installed VLBI equipment and measured the APEX station position to 1 cm accuracy (1 sigma). We then observed 3C 279 on 2012 May 7 in a 5 hour 230 GHz VLBI track with baseline lengths of 2800 M$\lambda$ to 7200 M$\lambda$ and a finest fringe spacing of 28.6 micro-arcseconds. Fringes were detected on all baselines with SNRs of 12 to 55 in 420 s. The correlated flux density on the longest baseline was ~0.3 Jy/beam, out of a total flux density of 19.8 Jy. Visibility data suggest an emission region <38 uas in size, and at least two components, possibly polarized. We find a lower limit of the brightness temperature of the inner jet region of about 10^10 K. Lastly, we find an upper limit of 20% on the linear polarization fraction at a fringe spacing of ~38 uas. With APEX the angular resolution of 230 GHz VLBI improves to 28.6 uas. This allows one to resolve the last-photon ring around the Galactic Center black hole event horizon, expected to be 40 uas in diameter, and probe radio jet launching at unprecedented resolution, down to a few gravitational radii in galaxies like M 87. To probe the structure in the inner parsecs of 3C 279 in detail, follow-up observations with APEX and five other mm-VLBI stations have been conducted (March 2013) and are being analyzed.Comment: accepted for publication in A&

Scientific Highlights of the HETE-2 Mission

The HETE-2 mission has been highly productive. It has observed more than 250 GRBs so far. It is currently localizing 25 - 30 GRBs per year, and has localized 43 GRBs to date. Twenty-one of these localizations have led to the detection of X-ray, optical, or radio afterglows, and as of now, 11 of the bursts with afterglows have known redshifts. HETE-2 has confirmed the connection between GRBs and Type Ic supernovae, a singular achievement and certainly one of the scientific highlights of the mission so far. It has provided evidence that the isotropic-equivalent energies and luminosities of GRBs are correlated with redshift, implying that GRBs and their progenitors evolve strongly with redshift. Both of these results have profound implications for the nature of GRB progenitors and for the use of GRBs as a probe of cosmology and the early universe. HETE-2 has placed severe constraints on any X-ray or optical afterglow of a short GRB. It is also solving the mystery of "optically dark' GRBs, and revealing the nature of X-ray flashes.Comment: 10 pages, 9 figures, to appear in proc. "The Restless High-Energy Universe", Royal Tropical Institute, Amsterdam; revised text, added ref