1,720,955 research outputs found

    Precise writing of human genomes: engineering & characterizing genome editors for programmable DNA integration in human cells

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    Methods for genome engineering have enabled construction of synthetic genomes, therapeutically reprogrammed cells, synthetic organs, and modification of human genomes. Design and discovery of genome editors has enabled programmed small deletions and insertions, however, tools for precise integration of large gene fragments are lacking. Towards this goal, we describe the development of a programmable transposase system that can integrate transgenes of >10kb precisely across cell types. We also describe a method for targeted integration with a refactored lentiviral vector via HDR, and exemplify the potential of targeted tissue delivery of lentiviral vectors via envelope protein pooled screening. We further describe a synthetic evolution platform that can be applied to improve genome editors. Finally, we describe the implementation of a method for whole genome characterization of insertions using long read sequencing, that can enable comprehensive characterization of engineered editors. These methods will enable new operations for therapeutic and biotechnological genome writing, and further development of improved editors.Les metodologies per a l'enginyeria genòmica han permès la construcció de genomes sintètics, la reprogramació terapèutica de cèl·lules, òrgans sintètics i l'edició d’humans. El disseny i descobriment d'editors genòmics ha possibilitat petites delecions i insercions programades, però encara falten eines per a la integració precisa de grans fragments de gens. Amb aquest objectiu, descrivim el desenvolupament d'un sistema de transposasa programable que pot integrar transgens de més de 10kb de manera precisa en diferents tipus de cèl·lules. També descrivim un mètode per a la integració dirigida mitjançant un vector lentiviral refactoritzat a través de HDR, i exemplifiquem el potencial de la lliurament de teixits objectiu de vectors lentivirals mitjançant la selecció de proteïnes d'envoltura i cribatge simultani. A més, descrivim una plataforma d'evolució sintètica per millorar els editors genòmics. Finalment, descrivim la implementació d'un mètode per a la caracterització completa del genoma de les insercions utilitzant seqüenciació de lectura llarga, que pot permetre una caracterització completa dels editors enginyeritzats. Aquestes metodologies permetran noves operacions per a l'escriptura genòmica terapèutica i biotecnològica, i el desenvolupament futur d'editors millorats.Programa de Doctorat en Biomedicin

    Precise writing of human genomes: engineering & characterizing genome editors for programmable DNA integration in human cells

    No full text
    Methods for genome engineering have enabled construction of synthetic genomes, therapeutically reprogrammed cells, synthetic organs, and modification of human genomes. Design and discovery of genome editors has enabled programmed small deletions and insertions, however, tools for precise integration of large gene fragments are lacking. Towards this goal, we describe the development of a programmable transposase system that can integrate transgenes of >10kb precisely across cell types. We also describe a method for targeted integration with a refactored lentiviral vector via HDR, and exemplify the potential of targeted tissue delivery of lentiviral vectors via envelope protein pooled screening. We further describe a synthetic evolution platform that can be applied to improve genome editors. Finally, we describe the implementation of a method for whole genome characterization of insertions using long read sequencing, that can enable comprehensive characterization of engineered editors. These methods will enable new operations for therapeutic and biotechnological genome writing, and further development of improved editors.Les metodologies per a l'enginyeria genòmica han permès la construcció de genomes sintètics, la reprogramació terapèutica de cèl·lules, òrgans sintètics i l'edició d’humans. El disseny i descobriment d'editors genòmics ha possibilitat petites delecions i insercions programades, però encara falten eines per a la integració precisa de grans fragments de gens. Amb aquest objectiu, descrivim el desenvolupament d'un sistema de transposasa programable que pot integrar transgens de més de 10kb de manera precisa en diferents tipus de cèl·lules. També descrivim un mètode per a la integració dirigida mitjançant un vector lentiviral refactoritzat a través de HDR, i exemplifiquem el potencial de la lliurament de teixits objectiu de vectors lentivirals mitjançant la selecció de proteïnes d'envoltura i cribatge simultani. A més, descrivim una plataforma d'evolució sintètica per millorar els editors genòmics. Finalment, descrivim la implementació d'un mètode per a la caracterització completa del genoma de les insercions utilitzant seqüenciació de lectura llarga, que pot permetre una caracterització completa dels editors enginyeritzats. Aquestes metodologies permetran noves operacions per a l'escriptura genòmica terapèutica i biotecnològica, i el desenvolupament futur d'editors millorats.Programa de Doctorat en Biomedicin

    Precise writing of human genomes: engineering & characterizing genome editors for programmable DNA integration in human cells

    No full text
    Methods for genome engineering have enabled construction of synthetic genomes, therapeutically reprogrammed cells, synthetic organs, and modification of human genomes. Design and discovery of genome editors has enabled programmed small deletions and insertions, however, tools for precise integration of large gene fragments are lacking. Towards this goal, we describe the development of a programmable transposase system that can integrate transgenes of >10kb precisely across cell types. We also describe a method for targeted integration with a refactored lentiviral vector via HDR, and exemplify the potential of targeted tissue delivery of lentiviral vectors via envelope protein pooled screening. We further describe a synthetic evolution platform that can be applied to improve genome editors. Finally, we describe the implementation of a method for whole genome characterization of insertions using long read sequencing, that can enable comprehensive characterization of engineered editors. These methods will enable new operations for therapeutic and biotechnological genome writing, and further development of improved editors.Les metodologies per a l'enginyeria genòmica han permès la construcció de genomes sintètics, la reprogramació terapèutica de cèl·lules, òrgans sintètics i l'edició d’humans. El disseny i descobriment d'editors genòmics ha possibilitat petites delecions i insercions programades, però encara falten eines per a la integració precisa de grans fragments de gens. Amb aquest objectiu, descrivim el desenvolupament d'un sistema de transposasa programable que pot integrar transgens de més de 10kb de manera precisa en diferents tipus de cèl·lules. També descrivim un mètode per a la integració dirigida mitjançant un vector lentiviral refactoritzat a través de HDR, i exemplifiquem el potencial de la lliurament de teixits objectiu de vectors lentivirals mitjançant la selecció de proteïnes d'envoltura i cribatge simultani. A més, descrivim una plataforma d'evolució sintètica per millorar els editors genòmics. Finalment, descrivim la implementació d'un mètode per a la caracterització completa del genoma de les insercions utilitzant seqüenciació de lectura llarga, que pot permetre una caracterització completa dels editors enginyeritzats. Aquestes metodologies permetran noves operacions per a l'escriptura genòmica terapèutica i biotecnològica, i el desenvolupament futur d'editors millorats.Programa de Doctorat en Biomedicin

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis

    Dispelling the Myths Behind First-author Citation Counts

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    We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more sophisticated methods

    Author Index

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    koamabayili/VECTRON-author-checklist: VECTRON author checklist

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    We have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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