1,720,956 research outputs found
“VIRAL VECTORS FOR THE MANIPULATION OF NEURONAL CIRCUITS”
The field of connectomics aims to map the complex network of specialized synaptic connections that coordinate the flow of information at different resolution levels. The microscopic level investigates the organization of single synapses; the mesoscopic one analyses the circuit-level architecture of neural populations and the macroscopic one takes into consideration the functional connectivity between large brain regions. In the past two decades considerable methodological advances have been made thanks to the synergy of molecular biology, genetics, virology, and microscopy in the development of viral vectors. They allow the investigation of complex network of specialized synaptic connections that coordinate the flow of information. These effective tools are bound to provide new insights on the neural basis of dysfunctional synaptic signaling and on brain dysconnectivity which both characterize developmental diseases such as autism spectrum disorder, schizophrenia and other disorders with developmental origins. Given the hypothesis that dynamics at synaptic level can reflect responses at whole brain level, I engineered viral vectors both to map, to manipulate and to monitor neural circuits, as well as to induce region-, time- and cell type-specific fluctuations. During my Ph.D. I started two projects, and I took part to a third ongoing project in collaboration with Dr. Alessandro Gozzi’s lab. These are three independent projects which will be described in separate chapters. To this aim I used three experimental strategies and evaluate different levels of investigation: i) site-specific recombinase-expressing vectors to specifically map and manipulate target neuronal populations at mesoscopic level; ii) viral vectors with Tet-On system to remotely control synaptic activity at microscopic level; iii) constitutively GFP-expressing vector to sparse labelling the whole brain and to correlate macroscopic functional connectivity to microscopic synaptic structural rearrangements.
i) With the first project, I performed a functional assay of progressive amino-terminal deleted Cre recombinase isoforms to implement recombinase-based technologies to study the structure and subsequently the function of a defined neuronal population avoiding unwanted somatic recombination due to “leakage” activity.
ii) In parallel, I studied the perturbations at microscopic synaptic level to test the hypothesis that cellular mechanisms of synaptic plasticity are link to the generation of activity patterns. To investigate the connection between synaptic dysregulation and functional dysconnectivity in mental disorders, I focused my attention on the thalamo-prefrontal projecting neurons of adult mice, since this circuitry dysfunction has been observed to lead to severe impairments in mental disorders such as autism, schizophrenia, and depression. To do so, I engineered a viral approach based on Dox-controlled genetic switches for remotely and reversibly promoting bidirectional control of synaptic strength at basal condition by the viral-encoding modulation of AMPA receptor subunits at the level of thalamo-prefrontal cortex circuit.
iii) Eventually, taking advantage of a mouse model of 22q11.2 connectopathy I probed mechanistic links between synaptic pathology and altered macroscale functional. A reporter-expressing viral vector has been used to highlight synaptic anatomic structures such as dendritic spines to correlate it with global activity analysis during development in 22q11.2 connectopathy. The observations about the correlation between synaptic activity and global functional activity complements microscale modeling and advances our understanding of 22q11.2 connectopathy, suggesting that disrupted synaptic homeostasis can lead to multiscale alterations in neural connectivity
Going Beyond Counting First Authors in Author Co-citation Analysis
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
“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
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
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
koamabayili/VECTRON-author-checklist: VECTRON author checklist
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
Author-wise bibliometric analysis based on entropy.
Author-wise bibliometric analysis based on entropy.</p
Author Under Sail The Imagination of Jack London, 1893-1902
In 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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