Probing Fine-Scale Ionospheric Structure with the Very Large Array Radio Telescope

High resolution (~1 arcminute) astronomical imaging at low frequency (below 150 MHz) has only recently become practical with the development of new calibration algorithms for removing ionospheric distortions. In addition to opening a new window in observational astronomy, the process of calibrating the ionospheric distortions also probes ionospheric structure in an unprecedented way. Here we explore one aspect of this new type of ionospheric measurement, the differential refraction of celestial source pairs as a function of their angular separation. This measurement probes variations in the spatial gradient of the line-of-sight total electron content (TEC) to 0.001 TECU/km accuracy over spatial scales of under 10 km to over 100 km. We use data from the VLA Low-frequency Sky Survey (VLSS; Cohen et al. 2007, AJ 134, 1245), a nearly complete 74 MHz survey of the entire sky visible to the Very Large Array (VLA) telescope in Socorro, New Mexico. These data comprise over 500 hours of observations, all calibrated in a standard way. While ionospheric spatial structure varies greatly from one observation to the next, when analyzed over hundreds of hours, statistical patterns become apparent. We present a detailed characterization of how the median differential refraction depends on source pair separation, elevation and time of day. We find that elevation effects are large, but geometrically predictable and can be "removed" analytically using a "thin-shell" model of the ionosphere. We find significantly greater ionospheric spatial variations during the day than at night. These diurnal variations appear to affect the larger angular scales to a greater degree indicating that they come from disturbances on relatively larger spatial scales (100s of km, rather than 10s of km).Comment: Accepted for publication by The Astronomical Journa

UV Filters with Antagonistic Action at Androgen Receptors in the MDA-kb2 Cell Transcriptional-Activation Assay

The fact that certain ultraviolet (UV) filters used in cosmetics display estrogenic activity prompted us to study potential actions on androgen receptors (AR) in the human breast carcinoma cell line MDA-kb2, which expresses functional endogenous AR and glucocorticoid receptors (GR) and is stably transfected with a luciferase reporter plasmid. Dihydrotestosterone (DHT), methyltrienolone (R1881), methyltestosterone, danazol, and androstenedione increased luciferase activity, with EC50 values between 0.11 nM (R1881), 0.14 nM (DHT), and 73.5 nM (androstenedione). DHT-induced luciferase gene expression was inhibited by nonsteroidal antiandrogens, hydroxyflutamide, flutamide, bicalutamide, and vinclozolin. In contrast, the steroidal AR agonist/antagonist cyproterone actetate showed agonistic activity in the absence and presence of DHT, which was not blocked by hydroxyflutamide and thus seems not to be mediated by AR. GR-mediated activation of luciferase by dexamethasone was 100 times less potent than DHT and was not antagonized by hydroxyflutamide. The cell line was used for screening of UV filters, benzophenone-3 (Bp-3), benzophenone-4, 3-benzylidene camphor, 4-methylbenzylidene camphor, butyl-methoxy-dibenzoylmethane, homosalate (HMS), octyl-dimethyl-PABA, and octyl-methoxycinnamate. Two of these, Bp-3 and HMS, antagonized DHT-induced AR activation below cytotoxic concentrations, with IC50 of 5.57 10−6 M (HMS) and 4.98 10−6 M (Bp-3). None of the eight UV filters displayed agonistic activity when tested alone, but high concentrations of Bp-3 induced an increase of luciferase activity in the presence of dexamethasone, which was not blocked by hydroxyflutamide or the estrogen antagonist, ICI 182,780. These data indicate that the UV filters Bp-3 and HMS possess antiandrogenic activity in vitro in addition to estrogenic activit

Radio astrometry with chromatic AGN core positions

Aims: The effect of frequency-dependent AGN core positions (``core-shifts'') on radio Very Long Baseline Interferometry (VLBI) global astrometry measurements is investigated. Methods: The basic equations relating to VLBI astrometry are reviewed, including the effects of source structure. A power-law representation of core-shifts, based on both observations and theoretical considerations of jet conditions, is incorporated. Results: It is shown that, in the presence of core-shifts, phase and group-delay astrometry measurements yield different positions. For a core displacement from the jet base parametrized by Delta x (lambda) = k lambda^beta group delays measure a ``reduced'' core-shift of (1-beta) Delta x (lambda). For the astrophysically-significant case of beta = 1, group delays measure no shift at all, giving the position of the jet base. At 8.4 GHz an estimated typical offset between phase and group-delay positions of ~170 uas is smaller than the current ~250 uas precision of group-delay positions of the sources used to define the ICRF; however, this effect must be taken into account for future measurements planned with improved accuracy when comparing with optical positions of AGN to be obtained with the GAIA mission.Comment: Accepted for publication in Astronomy & Astrophysics, 4 page

Polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene, intakes of folate and related B vitamins and colorectal cancer : a case-control study in a population with relatively low folate intake

Peer reviewedPublisher PD

A Multi-wavelength Study of the Sunyaev-Zel'dovich Effect in the Triple-Merger Cluster MACS J0717.5+3745 with MUSTANG and Bolocam

We present 90, 140, and 268GHz sub-arcminute resolution imaging of the Sunyaev-Zel'dovich effect (SZE) in MACSJ0717.5+3745. Our 90GHz SZE data result in a sensitive, 34uJy/bm map at 13" resolution using MUSTANG. Our 140 and 268GHz SZE imaging, with resolutions of 58" and 31" and sensitivities of 1.8 and 3.3mJy/beam respectively, was obtained using Bolocam. We compare these maps to a 2-dimensional pressure map derived from Chandra X-ray observations. Our MUSTANG data confirm previous indications from Chandra of a pressure enhancement due to shock-heated, >20keV gas immediately adjacent to extended radio emission seen in low-frequency radio maps. The MUSTANG data also detect pressure substructure that is not well-constrained by the X-ray data in the remnant core of a merging subcluster. We find that the small-scale pressure enhancements in the MUSTANG data amount to ~2% of the total pressure measured in the 140GHz Bolocam observations. The X-ray template also fails on larger scales to accurately describe the Bolocam data, particularly at the location of a subcluster known to have a high line of sight optical velocity (~3200km/s). Our Bolocam data are adequately described when we add an additional component - not described by a thermal SZE spectrum - coincident with this subcluster. Using flux densities extracted from our model fits, and marginalizing over the temperature constraints for the region, we fit a thermal+kinetic SZE spectrum to our data and find the subcluster has a best-fit line of sight proper velocity of 3600+3440/-2160km/s. This agrees with the optical velocity estimates for the subcluster. The probability of velocity<0 given our measurements is 2.1%. Repeating this analysis using flux densities measured non-parametrically results in a 3.4% probability of a velocity<=0. We note that this tantalizing result for the kinetic SZE is on resolved, subcluster scales.Comment: 10 Figures, 18 pages. this version corrects issues with the previous arXiv versio

Scaling properties of protein family phylogenies

One of the classical questions in evolutionary biology is how evolutionary processes are coupled at the gene and species level. With this motivation, we compare the topological properties (mainly the depth scaling, as a characterization of balance) of a large set of protein phylogenies with a set of species phylogenies. The comparative analysis shows that both sets of phylogenies share remarkably similar scaling behavior, suggesting the universality of branching rules and of the evolutionary processes that drive biological diversification from gene to species level. In order to explain such generality, we propose a simple model which allows us to estimate the proportion of evolvability/robustness needed to approximate the scaling behavior observed in the phylogenies, highlighting the relevance of the robustness of a biological system (species or protein) in the scaling properties of the phylogenetic trees. Thus, the rules that govern the incapability of a biological system to diversify are equally relevant both at the gene and at the species level.Comment: Replaced with final published versio

YAP/TAZ Activation Drives Uveal Melanoma Initiation and Progression

Uveal melanoma (UM), the most common ocular malignancy, is characterized by GNAQ/11 mutations. Hippo/YAP and Ras/mitogen-activated protein kinase (MAPK) emerge as two important signaling pathways downstream of G protein alpha subunits of the Q class (GalphaQ/11)-mediated transformation, although whether and how they contribute to UM genesis in vivo remain unclear. Here, we adapt an adeno-associated virus (AAV)-based ocular injection method to directly deliver Cre recombinase into the mouse uveal tract and demonstrate that Lats1/2 kinases suppress UM formation specifically in uveal melanocytes. We find that genetic activation of YAP, but not Kras, is sufficient to initiate UM. We show that YAP/TAZ activation induced by Lats1/2 deletion cooperates with Kras to promote UM progression via downstream transcriptional reinforcement. Furthermore, dual inhibition of YAP/TAZ and Ras/MAPK synergizes to suppress oncogenic growth of human UM cells. Our data highlight the functional significance of Lats-YAP/TAZ in UM initiation and progression in vivo and suggest combination inhibition of YAP/TAZ and Ras/MAPK as a new therapeutic strategy for UM

Maximum likelihood models and algorithms for gene tree evolution with duplications and losses

<p>Abstract</p> <p>Background</p> <p>The abundance of new genomic data provides the opportunity to map the location of gene duplication and loss events on a species phylogeny. The first methods for mapping gene duplications and losses were based on a parsimony criterion, finding the mapping that minimizes the number of duplication and loss events. Probabilistic modeling of gene duplication and loss is relatively new and has largely focused on birth-death processes.</p> <p>Results</p> <p>We introduce a new maximum likelihood model that estimates the speciation and gene duplication and loss events in a gene tree within a species tree with branch lengths. We also provide an, in practice, efficient algorithm that computes optimal evolutionary scenarios for this model. We implemented the algorithm in the program DrML and verified its performance with empirical and simulated data.</p> <p>Conclusions</p> <p>In test data sets, DrML finds optimal gene duplication and loss scenarios within minutes, even when the gene trees contain sequences from several hundred species. In many cases, these optimal scenarios differ from the lca-mapping that results from a parsimony gene tree reconciliation. Thus, DrML provides a new, practical statistical framework on which to study gene duplication.</p

Impact of breakfast on daily energy intake - an analysis of absolute versus relative breakfast calories

<p>Abstract</p> <p>Objective</p> <p>The role of breakfast energy in total daily energy intake is a matter of debate. Acute feeding experiments demonstrated that high breakfast energy leads to greater overall intake supported by cross-sectional data of a free-living population. On the other hand, a large intraindividual analysis has indicated that a high proportion of breakfast to overall intake is associated with lower daily energy intake. To evaluate these apparently contradictory results in greater detail both ways of analysis were applied to the same data set of dietary records.</p> <p>Methods</p> <p>On an intraindividual basis total daily energy intake was related to the absolute values of breakfast energy intake or to the ratio of breakfast to overall intake, respectively. Food intake of 280 obese and 100 normal weight subjects was analyzed who recorded over 10 (obese) or 14 (normal weight) consecutive days, respectively.</p> <p>Results</p> <p>Increasing breakfast energy was associated with greater overall intake in normal weight and obese subjects. The increasing ratio of breakfast to total daily energy intake was associated with a significant reduction of overall intake on days where post-breakfast energy was significantly reduced. Correlational and multiple regression analysis support the concept that absolute breakfast calories have the strongest influence on daily energy intake.</p> <p>Conclusion</p> <p>Reduced breakfast energy intake is associated with lower total daily intake. The influence of the ratio of breakfast to overall energy intake largely depends on the post-breakfast rather than breakfast intake pattern. Therefore, overweight and obese subjects should consider the reduction of breakfast calories as a simple option to improve their daily energy balance.</p