BL LAC PKSB1144-379 an extreme scintillator

Rapid variability in the radio flux density of the BL Lac object PKSB1144-379 has been observed at four frequencies, ranging from 1.5 to 15 GHz, with the VLA and the University of Tasmania's Ceduna antenna. Intrinsic and line of sight effects were examined as possible causes of this variability, with interstellar scintillation best explaining the frequency dependence of the variability timescales and modulation indices. This scintillation is consistent with a compact source 20-40 microarcseconds, or 0.15-0.3 pc in size. The inferred brightness temperature for PKSB1144-379 (assuming that the observed variations are due to scintillation) is 6.2e12 K at 4.9 GHz, with approximately 10 percent of the total flux in the scintillating component. We show that scintillation surveys aimed at identifying variability timescales of days to weeks are an effective way to identify the AGN with the highest brightness temperatures.Comment: 6 pages, 3 figures, accepted for publication in ApJ Letter

catena-Poly[[silver(I)-μ-N-(3-pyridyl­meth­yl)pyridine-4-carboxamide] nitrate monohydrate]

In the title compound, {[Ag(C12H11N3O)]NO3·H2O}n, the Ag atom is coordinated by two N atoms from the heterocyclic ligand, giving a linear polycationic chain. Two long Ag⋯Onitrate inter­actions [2.667 (3) and 2.840 (3) Å] result in a three-dimensional network. The water mol­ecule consolidates the network structure by forming hydrogen bonds, one to the polycationic chain and one to the nitrate anion

Oncogenic R132 IDH1 Mutations Limit NADPH for De Novo Lipogenesis through (D)2-Hydroxyglutarate Production in Fibrosarcoma Sells.

Neomorphic mutations in NADP-dependent isocitrate dehydrogenases (IDH1 and IDH2) contribute to tumorigenesis in several cancers. Although significant research has focused on the hypermethylation phenotypes associated with (D)2-hydroxyglutarate (D2HG) accumulation, the metabolic consequences of these mutations may also provide therapeutic opportunities. Here we apply flux-based approaches to genetically engineered cell lines with an endogenous IDH1 mutation to examine the metabolic impacts of increased D2HG production and altered IDH flux as a function of IDH1 mutation or expression. D2HG synthesis in IDH1-mutant cells consumes NADPH at rates similar to de novo lipogenesis. IDH1-mutant cells exhibit increased dependence on exogenous lipid sources for in vitro growth, as removal of medium lipids slows growth more dramatically in IDH1-mutant cells compared with those expressing wild-type or enzymatically inactive alleles. NADPH regeneration may be limiting for lipogenesis and potentially redox homeostasis in IDH1-mutant cells, highlighting critical links between cellular biosynthesis and redox metabolism

Precision Astrometry with the Very Long Baseline Array: Parallaxes and Proper Motions for 14 Pulsars

Astrometry can bring powerful constraints to bear on a variety of scientific questions about neutron stars, including their origins, astrophysics, evolution, and environments. Using phase-referenced observations at the VLBA, in conjunction with pulsar gating and in-beam calibration, we have measured the parallaxes and proper motions for 14 pulsars. The smallest measured parallax in our sample is 0.13+-0.02 mas for PSR B1541+09, which has a most probable distance of 7.2+1.3-1.1 kpc. We detail our methods, including initial VLA surveys to select candidates and find in-beam calibrators, VLBA phase-referencing, pulsar gating, calibration, and data reduction. The use of the bootstrap method to estimate astrometric uncertainties in the presence of unmodeled systematic errors is also described. Based on our new model-independent estimates for distance and transverse velocity, we investigate the kinematics and birth sites of the pulsars and revisit models of the Galactic electron density distribution. We find that young pulsars are moving away from the Galactic plane, as expected, and that age estimates from kinematics and pulsar spindown are generally in agreement, with certain notable exceptions. Given its present trajectory, the pulsar B2045-16 was plausibly born in the open cluster NGC 6604. For several high-latitude pulsars, the NE2001 electron density model underestimates the parallax distances by a factor of two, while in others the estimates agree with or are larger than the parallax distances, suggesting that the interstellar medium is irregular on relevant length scales. The VLBA astrometric results for the recycled pulsar J1713+0747 are consistent with two independent estimates from pulse timing, enabling a consistency check between the different reference frames.Comment: 16 pages, 9 figures, 4 tables; results unchanged; revised version accepted by Ap

Probing the Neutron Star Interior with Glitches

With the aim of constraining the structural properties of neutron stars and the equation of state of dense matter, we study sudden spin-ups, glitches, occurring in the Vela pulsar and in six other pulsars. We present evidence that glitches represent a self-regulating instability for which the star prepares over a waiting time. The angular momentum requirements of glitches in Vela indicate that at least 1.4% of the star's moment of inertia drives these events. If glitches originate in the liquid of the inner crust, Vela's `radiation radius' $R_\infty$ must exceed ~12 km for a mass of 1.4 solar masses. The isolated neutron star RX J18563-3754 is a promising candidate for a definitive radius measurement, and offers to further our understanding of dense matter and the origin of glitches.Comment: Invited talk at the Pacific Rim Conference on Stellar Astrophysics, Hong Kong, Aug. 1999. 9 pages, 5 figure

Transient radio bursts from rotating neutron stars

The `radio sky' is relatively unexplored for transient signals, although the potential of radio-transient searches is high, as demonstrated recently by the discovery of a previously unknown type of source which varies on timescales of minutes to hours. Here we report a new large-scale search for radio sources varying on much shorter timescales. This has revealed 11 objects characterized by single, dispersed bursts having durations between 2 and 30 ms. The average time intervals between bursts range from 4 minutes to 3 hours, with radio emission typically detectable for < 1 s per day. From an analysis of the burst arrival times, we have identified periodicities in the range 0.4 - 7 s for ten of the 11 sources, suggesting a rotating neutron star origin. Despite the small number of sources presently detected, their ephemeral nature implies a total Galactic population which significantly exceeds that of the regularly pulsing radio pulsars. Five of the ten sources have periods greater than 4 s, and period derivatives have been measured for three of the sources, with one having a very high inferred magnetic field of 5e13 G, suggesting that this new population is related to other classes of isolated neutron stars observed at X-ray and gamma-ray wavelengths.Comment: 10 pages, 4 figures. Accepted by Natur

Precision southern hemisphere VLBI pulsar astrometry II: Measurement of seven parallaxes

Accurate measurement of pulsar distances via astrometry using very long baseline interferometry enables the improvement of Galactic electron density distribution models, improving distance estimates for the vast majority of pulsars for which parallax measurements are unavailable. However, pulsars at southern declinations have been under-represented in previous interferometric astrometry campaigns. In order to redress this imbalance, we have conducted a two-year astrometric campaign targeting eight southern pulsars with the Australian Long Baseline Array. The program summarized in this paper has resulted in the measurement of seven new pulsar parallaxes, with success on objects down to a mean flux density of 0.8 mJy at 1600 MHz. Our results highlight the substantial uncertainties that remain when utilizing free electron density models for individual pulsar distances. Until this study, PSR J0630-2834 was believed to convert 16% of its spin-down energy into x-rays, but our measured parallax distance of 332 (+52 -40) pc has revised this value to <1%. In contrast, PSR J0108-1431 was found to be almost a factor of two more distant than previously thought, making its conversion of spin-down energy to x-rays the most efficient known (>1%). The 8.5 second radio pulsar J2144-3933 was found to be closer than previously predicted, making its apparent 1400 MHz radio luminosity the lowest of any known pulsar (20 microJy kpc^2). We have examined the growing population of neutron stars with accurate parallaxes to determine the effect of distance errors on the underlying neutron star velocity distribution, and find that typical distance errors may be biasing the estimated mean pulsar velocity upwards by 5%, and are likely to exaggerate the distribution's high-velocity tail.Comment: 37 pages, 14 figures, accepted by Ap

The IDV source J1128+5925, a new candidate for annual modulation?

Short time-scale radio variations of compact extragalactic radio sources, known as IntraDay Variability, can be explained in at least some sources by a source-extrinsic effect, in which the variations are interpreted as scintillation of radio waves caused by the turbulent ISM of the Milky Way. One of the most convincing observational arguments in favour of propagation-induced variability is the so called annual modulation of the characteristic variability time-scale, which is due to the orbital motion of the Earth. Data for the recently discovered and highly variable IDV source J1128+5925 are presented. We study the frequency and time dependence of the IDV in this compact quasar. We measure the characteristic variability time-scale of the IDV throughout the year, and analyze whether the observed changes in the variability time-scale are consistent with annual modulation. We monitored the flux density variability of J1128+5925 with dense time sampling between 2.7 and 10.45GHz with the 100m Effelsberg radio telescope of the MPIfR and with the 25m Urumqi radio telescope. From ten observing sessions, we determine the variability characteristics and time-scales. The observed pronounced changes of the variability time-scale of J1128+5925 are modelled with an anisotropic annual modulation model. The observed frequency dependence of the variation is in good agreement with the prediction from interstellar scintillation. Adopting a simple model for the annual modulation model and using also the frequency dependence of the IDV, we derive a lower limit to the distance of the scattering screen and an upper limit to the scintillating source size. The latter is found to be consistent with the measured core size from VLBI.Comment: 15 pages, 9 figures Accepted for publication in Astronomy and Astrophysic

The Small Molecule Inhibitor QLT0267 Radiosensitizes Squamous Cell Carcinoma Cells of the Head and Neck

BACKGROUND: The constant increase of cancer cell resistance to radio- and chemotherapy hampers improvement of patient survival and requires novel targeting approaches. Integrin-Linked Kinase (ILK) has been postulated as potent druggable cancer target. On the basis of our previous findings clearly showing that ILK transduces antisurvival signals in cells exposed to ionizing radiation, this study evaluated the impact of the small molecule inhibitor QLT0267, reported as putative ILK inhibitor, on the cellular radiation survival response of human head and neck squamous cell carcinoma cells (hHNSCC). METHODOLOGY/PRINCIPAL FINDINGS: Parental FaDu cells and FaDu cells stably transfected with a constitutively active ILK mutant (FaDu-IH) or empty vectors, UTSCC45 cells, ILK(floxed/floxed(fl/fl)) and ILK(-/-) mouse fibroblasts were used. Cells grew either two-dimensionally (2D) on or three-dimensionally (3D) in laminin-rich extracellular matrix. Cells were treated with QLT0267 alone or in combination with irradiation (X-rays, 0-6 Gy single dose). ILK knockdown was achieved by small interfering RNA transfection. ILK kinase activity, clonogenic survival, number of residual DNA double strand breaks (rDSB; gammaH2AX/53BP1 foci assay), cell cycle distribution, protein expression and phosphorylation (e.g. Akt, p44/42 mitogen-activated protein kinase (MAPK)) were measured. Data on ILK kinase activity and phosphorylation of Akt and p44/42 MAPK revealed a broad inhibitory spectrum of QLT0267 without specificity for ILK. QLT0267 significantly reduced basal cell survival and enhanced the radiosensitivity of FaDu and UTSCC45 cells in a time- and concentration-dependent manner. QLT0267 exerted differential, cell culture model-dependent effects with regard to radiogenic rDSB and accumulation of cells in the G2 cell cycle phase. Relative to corresponding controls, FaDu-IH and ILK(fl/fl) fibroblasts showed enhanced radiosensitivity, which failed to be antagonized by QLT0267. A knockdown of ILK revealed no change in clonogenic survival of the tested cell lines as compared to controls. CONCLUSIONS/SIGNIFICANCE: Our data clearly show that the small molecule inhibitor QLT0267 has potent cytotoxic and radiosensitizing capability in hHNSCC cells. However, QLT0267 is not specific for ILK. Further in vitro and in vivo studies are necessary to clarify the potential of QLT0267 as a targeted therapeutic in the clinic