305,266 research outputs found

    Secondary binding sites for triplex-forming oligonucleotides containing bulges, loops, and mismatches in the third strand

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    We have used DNase I footprinting to examine the binding of five different 17-mer oligonucleotides to a 53-base oligopurine tract containing four pyrimidine interruptions. Although all the expected triplexes formed with high affinity (Kd 10-50 nM), one oligonucleotide produced a footprint at a second site with about 20-fold lower affinity. We have explored the nature of this secondary binding site and suggest that it arises when each end of the third strand forms a 7-mer triplex with adjacent regions on the duplex, generating a contiguous 14-base triplex with a bulge in the center of the third strand oligonucleotide. This unusual binding mode was examined by use of oligonucleotides that were designed with the potential to form different length third-strand loops of various base composition. We find that triplexes containing single-base bulges are generally more stable than those with dinucleotide loops, though triplexes can be formed with loops of up to nine thymines, generating complexes with submicromolar dissociation constants. These structures are much more stable than those formed by adding two separate 7-mer oligonucleotides, which do not generate DNase I footprints, though a stable complex is generated when the two halves are covalently joined by a hexa(ethylene glycol) linker. MPE produces less clear footprints, presumably because this cleavage agent binds to triplex DNA, but confirms that the oligonucleotides can bind in unexpected places. These results suggest that extra care needs to be taken when designing long triplex-forming oligonucleotides so as to avoid triplex formation at shorter secondary sites

    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

    A positive proximal resection margin is associated with anastomotic complications following primary ileocaecal resection for Crohn's disease

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    Purposes: Bowel resection in patients with Crohn's disease (CD) has a high reported rate of postoperative complications and surgical recurrence. A macroscopically normal resection margin is recommended in CD surgery as wider margins do not translate in reduced recurrence rates. The aim of this study was to evaluate the association between resection margin status and anastomotic complications following ileocaecal resection for primary CD. Methods: All patients treated with ileocaecal resection for primary CD from 2010 to 2018 were included in this retrospective observational study. Emergency operations and recurrent CD were excluded. Patients in whom an anastomosis was not fashioned at the time of the surgery were also excluded. Histopathology data collected included macroscopic description, presence of macroscopic and microscopic involvement of the proximal and distal resection margins. The primary outcome was the rate of positive resection margin in patients who developed anastomotic complications (anastomotic leaks and intra-abdominal collections), and the secondary outcomes were overall complications rate, length of hospital stay, reoperations and rehospitalisation within 30 days. Results: A total of 104 patients were included. The proximal resection margin was microscopically involved in 19 patients (18.2%). Ten patients (9.6%) developed intra-abdominal anastomotic related complications, with 5 patients out of 10 (50%) in the group of postoperative anastomotic complications having a positive microscopic proximal margin at histology, compared to 14 patients (14.9%) in the group that did not develop anastomotic complications (p < 0.0001). Conclusions: Microscopic involvement of the proximal resection margin is more frequent in patients who develop postoperative anastomotic complications following elective ileocaecal resection for primary CD

    Oxygen-sensing mechanisms across eukaryotic kingdoms and their roles in complex multicellularity

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    Oxygen-sensing mechanisms of eukaryotic multicellular organisms coordinate hypoxic cellular responses in a spatiotemporal manner. Although this capacity partly allows animals and plants to acutely adapt to oxygen deprivation, its functional and historical roots in hypoxia emphasize a broader evolutionary role. For multicellular life-forms that persist in settings with variable oxygen concentrations, the capacity to perceive and modulate responses in and between cells is pivotal. Animals and higher plants represent the most complex life-forms that ever diversified on Earth, and their oxygen-sensing mechanisms demonstrate convergent evolution from a functional perspective. Exploring oxygen-sensing mechanisms across eukaryotic kingdoms can inform us on biological innovations to harness ever-changing oxygen availability at the dawn of complex life and its utilization for their organismal development

    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, publisher and bookseller : a tripartite synergy in Nigerian book industry

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    This work is about the roles of Author, Publisher and Bookseller in Book development in Nigeria. The paper started by delving into the history of Book Publishing in Nigeria after which it proceeded by defining who an author, a publisher, and a bookseller is and expatiated on the indispensable roles of these key actors in Nigerian Book Industry and in the emerging Information Society. Furthermore, the various constraints to book development were identified while the paper advised on how the Book Industry can be further promoted in Nigeria. However, the paper concluded and made recommendations on how the Book sector can help in enhancing scholarship in the country

    [Report to Chief J. E. Curry, by an unknown author #2]

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    Report to Chief J. E. Curry, by an unknown author. The report contains a list of officers who gave depositions to the United States Attorney

    [Report to Chief J. E. Curry, by an unknown author #1]

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    Report to Chief J. E. Curry, by an unknown author. The report contains a list of officers who gave depositions to the United States Attorney

    Mining e-mail content for author identification forensics

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    We describe an investigation into e-mail content mining for author identification, or authorship attribution, for the purpose of forensic investigation. We focus our discussion on the ability to discriminate between authors for the case of both aggregated e-mail topics as well as across different email topics. An extended set of e-mail document features including structural characteristics and linguistic patterns were derived and, together with a Support Vector Machine learning algorithm, were used for mining the e-mail content. Experiments using a number of e-mail documents generated by different authors on a set of topics gave promising results for both aggregated and multi-topic author categorisation
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