414 research outputs found

    Interface Development for Static Multimedia Documents

    Get PDF
    We propose to create a set of software technologies and encoding practices that will allow for the encoding, displaying, and searching of static documents that mix print, manuscript, and visual images--documents such as printed texts or images bearing handwritten annotations. The technologies we plan to build include standards for encoding coordinates in XML transcriptions so that search engines can visually display results of user searches for manuscript words and phrases; software for linking XML editing programs to an image display to allow encoders to relate bitmap images to XML text; and model stylesheets capable of displaying transcriptions of annotated documents together with digital images of those documents. The goal will be to create a software suite that is simple enough to be used by transcribers with little familiarity with information encoding and portable enough to work in multiple computing environments for widely different kinds of archival projects

    A Temperature-Sensitive Recombinant of Avian Coronavirus Infectious Bronchitis Virus Provides Complete Protection against Homologous Challenge

    Get PDF
    Avian coronavirus infectious bronchitis virus (IBV) is the etiological agent of infectious bronchitis, an acute highly contagious economically relevant respiratory disease of poultry. Vaccination is used to control IBV infections, with live-attenuated vaccines generated via serial passage of a virulent field isolate through embryonated hens' eggs. A fine balance must be achieved between attenuation and the retention of immunogenicity. The exact molecular mechanism of attenuation is unknown, and vaccines produced in this manner present a risk of reversion to virulence as few consensus level changes are acquired. Our previous research resulted in the generation of a recombinant IBV (rIBV) known as M41-R, based on a pathogenic strain M41-CK. M41-R was attenuated in vivo by two amino acid changes, Nsp10-Pro85Leu and Nsp14-Val393Leu; however, the mechanism of attenuation was not determined. Pro85 and Val393 were found to be conserved among not only IBV strains but members of the wider coronavirus family. This study demonstrates that the same changes are associated with a temperature-sensitive (ts) replication phenotype at 41°C in vitro, suggesting that the two phenotypes may be linked. Vaccination of specific-pathogen-free chickens with M41-R induced 100% protection against clinical disease, tracheal ciliary damage, and challenge virus replication following homologous challenge with virulent M41-CK. Temperature sensitivity has been used to rationally attenuate other viral pathogens, including influenza, and the identification of amino acid changes that impart both a ts and an attenuated phenotype may therefore offer an avenue for future coronavirus vaccine development. IMPORTANCE Infectious bronchitis virus is a pathogen of economic and welfare concern for the global poultry industry. Live-attenuated vaccines against are generated by serial passage of a virulent isolate in embryonated eggs until attenuation is achieved. The exact mechanisms of attenuation are unknown, and vaccines produced have a risk of reversion to virulence. Reverse genetics provides a method to generate vaccines that are rationally attenuated and are more stable with respect to back selection due to their clonal origin. Genetic populations resulting from molecular clones are more homogeneous and lack the presence of parental pathogenic viruses, which generation by multiple passage does not. In this study, we identified two amino acids that impart a temperature-sensitive replication phenotype. Immunogenicity is retained and vaccination results in 100% protection against homologous challenge. Temperature sensitivity, used for the development of vaccines against other viruses, presents a method for the development of coronavirus vaccines

    Temperature Sensitivity: A Potential Method for the Generation of Vaccines against the Avian Coronavirus Infectious Bronchitis Virus.

    Get PDF
    The Gammacoronavirus infectious bronchitis virus (IBV) is a highly contagious economically important respiratory pathogen of domestic fowl. Reverse genetics allows for the molecular study of pathogenic determinants to enable rational vaccine design. The recombinant IBV (rIBV) Beau-R, a molecular clone of the apathogenic Beaudette strain, has previously been investigated as a vaccine platform. To determine tissues in which Beau-R could effectively deliver antigenic genes, an in vivo study in chickens, the natural host, was used to compare the pattern of viral dissemination of Beau-R to the pathogenic strain M41-CK. Replication of Beau-R was found to be restricted to soft tissue within the beak, whereas M41-CK was detected in beak tissue, trachea and eyelid up to seven days post infection. In vitro assays further identified that, unlike M41-CK, Beau-R could not replicate at 41 °C, the core body temperature of a chicken, but is able to replicate a 37 °C, a temperature relatable to the very upper respiratory tract. Using a panel of rIBVs with defined mutations in the structural and accessory genes, viral replication at permissive and non-permissive temperatures was investigated, identifying that the Beau-R replicase gene was a determinant of temperature sensitivity and that sub-genomic mRNA synthesis had been affected. The identification of temperature sensitive allelic lesions within the Beau-R replicase gene opens up the possibility of using this method of attenuation in other IBV strains for future vaccine development as well as a method to investigate the functions of the IBV replicase proteins

    The powers in PowerPoint: Embedded authorities, documentary tastes, and institutional (second) orders in corporate Korea

    Get PDF
    Microsoft PowerPoint is both the bane and banality of contemporary South Korean office work. Corporate workers spend countless hours refining and crafting plans, proposals, and reports in PowerPoint that often lead to conflicts with coworkers and overtime work. This article theorizes the excessive attention to documents in modern office contexts. Where scholars have been under the impression that institutional documents align with institutional purposes, I describe a context in which making documents for individual purposes and making them for work exist under a basic tension. Based on fieldwork in corporate Korea between 2013 and 2015, I describe how Korean office workers calibrate documents to the tastes of superiors who populate the managerial chain. These practices leave little trace of real "work" on paper, but they are productive for navigating complex internal labor markets and demonstrating a higher order value of attention toward others. These findings suggest that institutional and individual authorities are not competing projects inside organizations but become entangled in increasingly complex participatory encounters, even as they are channeled through a seemingly simple software like PowerPoint. [documents, expertise, authority, technology, South Korea

    The domesticated transposase ALP2 mediates formation of a novel Polycomb protein complex by direct interaction with MSI1, a core subunit of Polycomb Repressive Complex 2 (PRC2)

    Get PDF
    A large fraction of plant genomes is composed of transposable elements (TE), which provide a potential source of novel genes through "domestication"-the process whereby the proteins encoded by TE diverge in sequence, lose their ability to catalyse transposition and instead acquire novel functions for their hosts. In Arabidopsis, ANTAGONIST OF LIKE HETEROCHROMATIN PROTEIN 1 (ALP1) arose by domestication of the nuclease component of Harbinger class TE and acquired a new function as a component of POLYCOMB REPRESSIVE COMPLEX 2 (PRC2), a histone H3K27me3 methyltransferase involved in regulation of host genes and in some cases TE. It was not clear how ALP1 associated with PRC2, nor what the functional consequence was. Here, we identify ALP2 genetically as a suppressor of Polycomb-group (PcG) mutant phenotypes and show that it arose from the second, DNA binding component of Harbinger transposases. Molecular analysis of PcG compromised backgrounds reveals that ALP genes oppose silencing and H3K27me3 deposition at key PcG target genes. Proteomic analysis reveals that ALP1 and ALP2 are components of a variant PRC2 complex that contains the four core components but lacks plant-specific accessory components such as the H3K27me3 reader LIKE HETEROCHROMATION PROTEIN 1 (LHP1). We show that the N-terminus of ALP2 interacts directly with ALP1, whereas the C-terminus of ALP2 interacts with MULTICOPY SUPPRESSOR OF IRA1 (MSI1), a core component of PRC2. Proteomic analysis reveals that in alp2 mutant backgrounds ALP1 protein no longer associates with PRC2, consistent with a role for ALP2 in recruitment of ALP1. We suggest that the propensity of Harbinger TE to insert in gene-rich regions of the genome, together with the modular two component nature of their transposases, has predisposed them for domestication and incorporation into chromatin modifying complexes

    Developing fit-for-purpose self-report instruments for assessing consumer responses to tobacco and nicotine products: the ABOUTℱ Toolbox initiative [version 1; referees: 2 approved]

    Get PDF
    Background. Determining the public health impact of tobacco harm reduction strategies requires the assessment of consumer perception and behavior associated with tobacco and nicotine products (TNPs) with different exposure and risk profiles. In this context, rigorous methods to develop and validate psychometrically sound self-report instruments to measure consumers’ responses to TNPs are needed. Methods. Consistent with best practice guidelines, including the U.S. Food and Drug Administration’s “Guidance for Industry Patient-Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims,” scientifically designed, fit-for-purpose, reliable, and valid instruments are now being applied to tobacco regulatory research. Results. This brief report presents the ABOUTℱ Toolbox (Assessment of Behavioral OUtcomes related to Tobacco and nicotine products) initiative. This communication: (1) describes the methodological steps followed for the development and validation of the measurement instruments included in the ABOUTℱ Toolbox, (2) presents a summary of the high-priority tobacco-related domains that are currently covered in the ABOUTℱ Toolbox (i.e., risk perception, dependence, product experience, health and functioning, and use history), and (3) details how the measurement instruments are made accessible to the scientific community. Conclusions. By making the ABOUTℱ Toolbox available to the tobacco research and public health community, we envision a rapidly expanding knowledge base, with the goals of (1) supporting consumer perception and behavior research to allow comparisons across a wide spectrum of TNPs, (2) enabling public health and regulatory communities to make better-informed decisions for future regulation of TNPs, and (3) enhancing surveillance activities associated with the impact of TNPs on population health

    CryoSat Ice Baseline-D validation and evolutions

    Get PDF
    The ESA Earth Explorer CryoSat-2 was launched on 8 April 2010 to monitor the precise changes in the thickness of terrestrial ice sheets and marine floating ice. To do that, CryoSat orbits the planet at an altitude of around 720 km with a retrograde orbit inclination of 92∘ and a quasi repeat cycle of 369 d (30 d subcycle). To reach the mission goals, the CryoSat products have to meet the highest quality standards to date, achieved through continual improvements of the operational processing chains. The new CryoSat Ice Baseline-D, in operation since 27 May 2019, represents a major processor upgrade with respect to the previous Ice Baseline-C. Over land ice the new Baseline-D provides better results with respect to the previous baseline when comparing the data to a reference elevation model over the Austfonna ice cap region, improving the ascending and descending crossover statistics from 1.9 to 0.1 m. The improved processing of the star tracker measurements implemented in Baseline-D has led to a reduction in the standard deviation of the point-to-point comparison with the previous star tracker processing method implemented in Baseline-C from 3.8 to 3.7 m. Over sea ice, Baseline-D improves the quality of the retrieved heights inside and at the boundaries of the synthetic aperture radar interferometric (SARIn or SIN) acquisition mask, removing the negative freeboard pattern which is beneficial not only for freeboard retrieval but also for any application that exploits the phase information from SARIn Level 1B (L1B) products. In addition, scatter comparisons with the Beaufort Gyre Exploration Project (BGEP; https://www.whoi.edu/beaufortgyre, last access: October 2019) and Operation IceBridge (OIB; Kurtz et al., 2013) in situ measurements confirm the improvements in the Baseline-D freeboard product quality. Relative to OIB, the Baseline-D freeboard mean bias is reduced by about 8 cm, which roughly corresponds to a 60 % decrease with respect to Baseline-C. The BGEP data indicate a similar tendency with a mean draft bias lowered from 0.85 to −0.14 m. For the two in situ datasets, the root mean square deviation (RMSD) is also well reduced from 14 to 11 cm for OIB and by a factor of 2 for the BGEP. Observations over inland waters show a slight increase in the percentage of good observations in Baseline-D, generally around 5 %–10 % for most lakes. This paper provides an overview of the new Level 1 and Level 2 (L2) CryoSat Ice Baseline-D evolutions and related data quality assessment, based on results obtained from analyzing the 6-month Baseline-D test dataset released to CryoSat expert users prior to the final transfer to operations

    CryoSat ocean product quality status and future evolution

    Get PDF
    The main objectives of this paper are to present the status of the CryoSat ocean products and to give an overview of all associated quality control and validation activities. Launched in 2010, the polar-orbiting European Space Agency’s (ESA) CryoSat mission was primarily developed to measure changes in the thickness of polar sea ice and elevation of the ice sheets. Going beyond its ice-monitoring objective, CryoSat is also a valuable source of data for the oceanographic community. The satellite’s radar altimeter can measure high-resolution geophysical parameters from the open ocean to the coast. To enable their full scientific and operational exploitation, the ocean products continuously evolve and need to be quality-controlled and thoroughly validated via science-oriented diagnostics based on multi-platform in situ data, models and other satellite missions. In support to ESA, the CryoSat ocean validation teams conduct this quality assessment for both the near real time and offline ocean products, both over short time scales (daily and monthly monitoring) and long-term stability (annual trends). Based on the outcomes from these quality analyses and feedback from scientific oceanographic community, ESA intends to upgrade the CryoSat Ocean processing chain for Autumn 2017

    Gene-specific ACMG/AMP classification criteria for germline APC variants: recommendations from the ClinGen InSIGHT Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel

    Get PDF
    Purpose The Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel (VCEP) was established by the International Society for Gastrointestinal Hereditary Tumours and the Clinical Genome Resource, who set out to develop recommendations for the interpretation of germline APC variants underlying Familial Adenomatous Polyposis, the most frequent hereditary polyposis syndrome. Methods Through a rigorous process of database analysis, literature review, and expert elicitation, the APC VCEP derived gene-specific modifications to the ACMG/AMP (American College of Medical Genetics and Genomics and Association for Molecular Pathology) variant classification guidelines and validated such criteria through the pilot classification of 58 variants. Results The APC-specific criteria represented gene- and disease-informed specifications, including a quantitative approach to allele frequency thresholds, a stepwise decision tool for truncating variants, and semiquantitative evaluations of experimental and clinical data. Using the APC-specific criteria, 47% (27/58) of pilot variants were reclassified including 14 previous variants of uncertain significance (VUS). Conclusion The APC-specific ACMG/AMP criteria preserved the classification of well-characterized variants on ClinVar while substantially reducing the number of VUS by 56% (14/25). Moving forward, the APC VCEP will continue to interpret prioritized lists of VUS, the results of which will represent the most authoritative variant classification for widespread clinical use

    The Gemini Cluster Astrophysics Spectroscopic Survey (GCLASS): The Role of Environment and Self-Regulation in Galaxy Evolution at z ~ 1

    Get PDF
    We evaluate the effects of environment and stellar mass on galaxy properties at 0.85 < z < 1.20 using a 3.6um-selected spectroscopic sample of 797 cluster and field galaxies drawn from the GCLASS survey. We confirm that for galaxies with LogM* > 9.3 the well-known correlations between environment and properties such as star-forming fraction (f_SF), SFR, SSFR, D(4000), and color are already in place at z ~ 1. We separate the effects of environment and stellar mass on galaxies by comparing the properties of star-forming and quiescent galaxies at fixed environment, and fixed stellar mass. The SSFR of star-forming galaxies at fixed environment is correlated with stellar mass; however, at fixed stellar mass it is independent of environment. The same trend exists for the D(4000) measures of both the star-forming and quiescent galaxies and shows that their properties are determined primarily by their stellar mass, not by their environment. Instead, it appears that environment's primary role is to control the fraction of star-forming galaxies. Using the spectra we identify candidate poststarburst galaxies and find that those with 9.3 < LogM* < 10.7 are 3.1 +/- 1.1 times more common in high-density regions compared to low-density regions. The clear association of poststarbursts with high-density regions as well as the lack of a correlation between the SSFRs and D(4000)s of star-forming galaxies with their environment suggests that at z ~ 1 the environmental-quenching timescale must be rapid. Lastly, we construct a simple quenching model which demonstrates that the lack of a correlation between the D(4000) of quiescent galaxies and their environment results naturally if self quenching dominates over environmental quenching at z > 1, or if the evolution of the self-quenching rate mirrors the evolution of the environmental-quenching rate at z > 1, regardless of which dominates.Comment: 26 pages, 15 figures, accepted for publication in Ap
    • 

    corecore