1,692 research outputs found

    Events and Controversies: Influences of a Shocking News Event on Information Seeking

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    It has been suggested that online search and retrieval contributes to the intellectual isolation of users within their preexisting ideologies, where people's prior views are strengthened and alternative viewpoints are infrequently encountered. This so-called "filter bubble" phenomenon has been called out as especially detrimental when it comes to dialog among people on controversial, emotionally charged topics, such as the labeling of genetically modified food, the right to bear arms, the death penalty, and online privacy. We seek to identify and study information-seeking behavior and access to alternative versus reinforcing viewpoints following shocking, emotional, and large-scale news events. We choose for a case study to analyze search and browsing on gun control/rights, a strongly polarizing topic for both citizens and leaders of the United States. We study the period of time preceding and following a mass shooting to understand how its occurrence, follow-on discussions, and debate may have been linked to changes in the patterns of searching and browsing. We employ information-theoretic measures to quantify the diversity of Web domains of interest to users and understand the browsing patterns of users. We use these measures to characterize the influence of news events on these web search and browsing patterns

    The VTI1A-TCF4 colon cancer fusion protein is a dominant negative regulator of Wnt signaling and is transcriptionally regulated by intestinal homeodomain factor CDX2

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    <div><p>Sequencing of primary colorectal tumors has identified a gene fusion in approximately 3% of colorectal cancer patients of the <i>VTI1A</i> and <i>TCF7L2</i> genes, encoding a VTI1A-TCF4 fusion protein containing a truncated TCF4. As dysregulation of the Wnt signaling pathway is associated with colorectal cancer development and progression, the functional properties and transcriptional regulation of the VTI1A-TCF4 fusion protein may also play a role in these processes. Functional characteristics of the VTI1A-TCF4 fusion protein in Wnt signaling were analyzed in NCI-H508 and LS174T colon cancer cell lines. The NCI-H508 cell line, containing the <i>VTI1A</i>-<i>TCF7L2</i> fusion gene, showed no active Wnt signaling, and overexpression of the VTI1A-TCF4 fusion protein in LS174T cells along with a Wnt signaling luciferase reporter plasmid showed inhibition of activity. The transcriptional regulation of the <i>VTI1A-TCF4</i> fusion gene was investigated in LS174T cells where the activity of the <i>VTI1A</i> promoter was compared to that of the <i>TCF7L2</i> promoter, and the transcription factor CDX2 was analyzed for gene regulatory activity of the <i>VTI1A</i> promoter through luciferase reporter gene assay using colon cancer cell lines as a model. Transfection of LS174T cells showed that the <i>VTI1A</i> promoter is highly active compared to the <i>TCF7L2</i> promoter, and that CDX2 activates transcription of <i>VTI1A</i>. These results suggest that the VTI1A-TCF4 fusion protein is a dominant negative regulator of the Wnt signaling pathway, and that transcription of <i>VTI1A</i> is activated by CDX2.</p></div

    Radio Interferometric Planet Search II: Constraints on sub-Jupiter-Mass Companions to GJ 896A

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    We present results from the Radio Interferometric Planet (RIPL) search for compan- ions to the nearby star GJ 896A. We present 11 observations over 4.9 years. Fitting astrometric parameters to the data reveals a residual with peak-to-peak amplitude of ~ 3 mas in right ascension. This residual is well-fit by an acceleration term of 0.458 \pm 0.032 mas/y^2. The parallax is fit to an accuracy of 0.2 mas and the proper motion terms are fit to accuracies of 0.01 mas/y. After fitting astrometric and acceleration terms residuals are 0.26 mas in each coordinate, demonstrating that stellar jitter does not limit the ability to carry out radio astrometric planet detection and characterization. The acceleration term originates in part from the companion GJ 896B but the amplitude of the acceleration in declination is not accurately predicted by the orbital model. The acceleration sets a mass upper limit of 0.15 MJ at a semi-major axis of 2 AU for a planetary companion to GJ 896A. For semi-major axes between 0.3 and 2 AU upper limits are determined by the maximum angular separation; the upper limits scale from the minimum value in proportion to the inverse of the radius. Upper limits at larger radii are set by the acceleration and scale as the radius squared. An improved solution for the stellar binary system could improve the exoplanet mass sensitivity by an order of magnitude.Comment: Accepted for publication in Ap

    Assay and heterologous expression in Pichia pastoris of plant cell wall type-II membrane anchored glycosyltransferases

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    Two Arabidopsis xylosyltransferases, designated RGXT1 and RGXT2, were recently expressed in Baculovirus transfected insect cells and by use of the free sugar assay shown to catalyse transfer of D-xylose from UDP-α-D-xylose to L-fucose and derivatives hereof. We have now examined expression of RGXT1 and RGXT2 in Pichia pastoris and compared the two expression systems. Pichia transformants, expressing soluble, secreted forms of RGXT1 and RGXT2 with an N- or C-terminal Flag-tag, accumulated recombinant, hyper-glycosylated proteins at levels between 6 and 16 mg protein • L-1 in the media fractions. When incubated with 0.5 M L-fucose and UDP-D-xylose all four RGXT1 and RGXT2 variants catalyzed transfer of D-xylose onto L-fucose with estimated turnover numbers between 0.15 and 0.3 sec-1, thus demonstrating that a free C-terminus is not required for activity. N- and O-glycanase treatment resulted in deglycosylation of all four proteins, and this caused a loss of xylosyltransferase activity for the C-terminally but not the N-terminally Flag-tagged proteins. The RGXT1 and RGXT2 proteins displayed an absolute requirement for Mn2+ and were active over a broad pH range. Simple dialysis of media fractions or purification on phenyl Sepharose columns increased enzyme activities 2-8 fold enabling direct verification of the product formed in crude assay mixtures using electrospray ionization mass spectrometry. Pichia expressed and dialysed RGXT variants yielded activities within the range 0.011 to 0.013 U (1 U = 1 nmol conversion of substrate • min-1 • µl medium-1) similar to those of RGXT1 and RGXT2 expressed in Baculovirus transfected insect Sf9 cells. In summary, the data presented suggest that Pichia is an attractive host candidate for expression of plant glycosyltransferases

    The Primordial Inflation Polarization Explorer (PIPER)

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    The Primordial Inflation Polarization Explorer (PIPER) is a balloon-borne cosmic microwave background (CMB) polarimeter designed to search for evidence of inflation by measuring the large-angular scale CMB polarization signal. BICEP2 recently reported a detection of B-mode power corresponding to the tensor-to-scalar ratio r = 0.2 on ~2 degree scales. If the BICEP2 signal is caused by inflationary gravitational waves (IGWs), then there should be a corresponding increase in B-mode power on angular scales larger than 18 degrees. PIPER is currently the only suborbital instrument capable of fully testing and extending the BICEP2 results by measuring the B-mode power spectrum on angular scales θ\theta = ~0.6 deg to 90 deg, covering both the reionization bump and recombination peak, with sensitivity to measure the tensor-to-scalar ratio down to r = 0.007, and four frequency bands to distinguish foregrounds. PIPER will accomplish this by mapping 85% of the sky in four frequency bands (200, 270, 350, 600 GHz) over a series of 8 conventional balloon flights from the northern and southern hemispheres. The instrument has background-limited sensitivity provided by fully cryogenic (1.5 K) optics focusing the sky signal onto four 32x40-pixel arrays of time-domain multiplexed Transition-Edge Sensor (TES) bolometers held at 140 mK. Polarization sensitivity and systematic control are provided by front-end Variable-delay Polarization Modulators (VPMs), which rapidly modulate only the polarized sky signal at 3 Hz and allow PIPER to instantaneously measure the full Stokes vector (I, Q, U, V) for each pointing. We describe the PIPER instrument and progress towards its first flight.Comment: 11 pages, 7 figures. To be published in Proceedings of SPIE Volume 9153. Presented at SPIE Astronomical Telescopes + Instrumentation 2014, conference 915

    The GalNAc-type O-Glycoproteome of CHO Cells Characterized by the SimpleCell Strategy

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    The Chinese hamster ovary cell (CHO) is the major host cell factory for recombinant production of biological therapeutics primarily because of its “human-like” glycosylation features. CHO is used for production of several O-glycoprotein therapeutics including erythropoietin, coagulation factors, and chimeric receptor IgG1-Fc-fusion proteins, however, some O-glycoproteins are not produced efficiently in CHO. We have previously shown that the capacity for O-glycosylation of proteins can be one limiting parameter for production of active proteins in CHO. Although the capacity of CHO for biosynthesis of glycan structures (glycostructures) on glycoproteins are well established, our knowledge of the capacity of CHO cells for attaching GalNAc-type O-glycans to proteins (glycosites) is minimal. This type of O-glycosylation is one of the most abundant forms of glycosylation, and it is differentially regulated in cells by expression of a subset of homologous polypeptide GalNAc-transferases. Here, we have genetically engineered CHO cells to produce homogeneous truncated O-glycans, so-called SimpleCells, which enabled lectin enrichment of O-glycoproteins and characterization of the O-glycoproteome. We identified 738 O-glycoproteins (1548 O-glycosites) in cell lysates and secretomes providing the first comprehensive insight into the O-glycosylation capacity of CHO (http://glycomics.ku.dk/o-glycoproteome_db/)

    Southern San Andreas-San Jacinto fault system slip rates estimated from earthquake cycle models constrained by GPS and interferometric synthetic aperture radar observations

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    We use ground geodetic and interferometric synthetic aperture radar satellite observations across the southern San Andreas (SAF)-San Jacinto (SJF) fault systems to constrain their slip rates and the viscosity structure of the lower crust and upper mantle on the basis of periodic earthquake cycle, Maxwell viscoelastic, finite element models. Key questions for this system are the SAF and SJF slip rates, the slip partitioning between the two main branches of the SJF, and the dip of the SAF. The best-fitting models generally have a high-viscosity lower crust (η = 10^(21) Pa s) overlying a lower-viscosity upper mantle (η = 10^(19) Pa s). We find considerable trade-offs between the relative time into the current earthquake cycle of the San Jacinto fault and the upper mantle viscosity. With reasonable assumptions for the relative time in the earthquake cycle, the partition of slip is fairly robust at around 24–26 mm/a for the San Jacinto fault system and 16–18 mm/a for the San Andreas fault. Models for two subprofiles across the SAF-SJF systems suggest that slip may transfer from the western (Coyote Creek) branch to the eastern (Clark-Superstition hills) branch of the SJF from NW to SE. Across the entire system our best-fitting model gives slip rates of 2 ± 3, 12 ± 9, 12 ± 9, and 17 ± 3 mm/a for the Elsinore, Coyote Creek, Clark, and San Andreas faults, respectively, where the large uncertainties in the slip rates for the SJF branches reflect the large uncertainty in the slip rate partitioning within the SJF system
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