1,720,960 research outputs found
DNA tools for imaging and manipulation of biological samples
No full textSpatial organization within biological systems is important for understanding mechanisms underlying health and disease. This thesis investigates the role of spatial distribution at cellular and molecular levels, utilizing DNA-based tools to elucidate its impact on receptor activation and creating methods for studying spatial organization of cells. The research of this thesis is structured into three studies, two focusing on clustering receptors with the aim of inducing apoptosis, one focusing on imaging and mapping cells with their transcriptomic contents.In Paper I, we investigate the spatial clustering of Death Receptor 5 (DR5) on cellular surfaces, examining its significance in the induction of apoptosis. The study demonstrates that a hexagonal arrangement of DR5-binding peptides on DNA origami structures can induce apoptosis. We identify that a 6 nm spacing in this hexagonal shape is the optimal peptide spacing for apoptosis induction. This finding highlights the significance of spatial organization in receptor signaling and introduces DNA origami as a potential platform for cancer therapy.Paper II expands on the foundation laid in Paper I with the development of a pH- sensitive DNA origami structure capable of selective DR5 activation in acidic tumor environments by using Triplex Forming Oligos (TFOs). This structure dynamically presents DR5-binding peptides in response to pH variations, thereby concentrating apoptotic activity within tumor sites where pH is lower than that of the normal physiological value. We demonstrate that the TFO forms a triplex at pH 6.5, but not pH 7.4, and can do so repeatedly. Furthermore, we demonstrate that this structure can induce apoptosis in cancer cells at pH 6.5, but not at pH 7.4, and does not induce apoptosis in other cell types at pH 7.4 either. Finally, we also show that injection of this structure into mice with growing tumors creates a reduction in tumor growth. The efficacy of this approach in inducing targeted apoptosis underscores the therapeutic potential of responsive DNA origami drug delivery systems.In paper III, we propose a novel method for spatial transcriptomics that enables the mapping of DNA spatial organization without the use of optics. Through PCR and DNA sequencing, this technique allows us to generate a spatial map of biological samples, overlayed with transcriptomic data to illustrate the spatial distribution of gene expression. We demonstrate the capacity of this method to create pure sequencing libraries. Furthermore, we show that this technique can reconstruct spatial location of artificially placed targets, preserving their relative spatial relations to each other. This method offers a potential new way for examining spatial dimensions of cellular function and gene expression.This thesis presents DNA-based methods in which the spatial organization of biological samples can be investigated or manipulated. The studies contribute to the advancement of targeted therapeutic interventions and spatial transcriptomics, offering insights that could inform future research and applications in biotechnology and medicine.List of scientific papersI. Yang Wang, Igor Baars, Ferenc Fördös, Björn Högberg. Clustering of Death Receptor for Apoptosis Using Nanoscale Patterns of Peptides. ACS Nano. 2021, 15(6), 9614−9626. https://doi.org/10.1021/acsnano.0c10104 II. Yang Wang, Igor Baars, Iris Rocamonde Lago, Yunshi Yang, Ieva Berzina, Keying Zhu, Marco Lolaico, Boxuan Shen, Robert A Harris, Björn Högberg. Peptide-pattern display from DNA origami driven by cancer acidity for selective apoptosis. Nature Nanotechnology. [Accepted]III. Igor Baars, Alexander Kloosterman, Marco Lolaico, Jakub Horváth, Anna Andersson, and Björn Högberg. Spatial reconstruction of a patterned sample using in situ PCR and DNA sequencing. [Manuscript]</p
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Get PDF“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
Get PDFWe 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
Get PDFWe 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
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe 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
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
Author Under Sail The Imagination of Jack London, 1893-1902
No full textIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Intro -- Title Page -- Copyright Page -- Dedication -- Contents -- Acknowledgments -- Introduction -- 1. Spirit Truth -- 2. From Absorption to Theatricality and Back Again -- 3. "I Will Build a New Present" -- 4. Sons as Authors -- 5. Fathers as Publishers -- 6. The Daughter as Author -- 7. Lovers as Authors -- 8. At Sea with the Family -- 9. Yellow News, Yellow Stories -- 10. The Return Home -- Notes -- Bibliography -- Index -- About Jay WilliamsIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Description based on publisher supplied metadata and other sources.Electronic reproduction. Ann Arbor, Michigan : ProQuest Ebook Central, YYYY. Available via World Wide Web. Access may be limited to ProQuest Ebook Central affiliated libraries
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