1,720,957 research outputs found
Efficient and targeted de-epithelialization as novel therapeutic strategy for lung regeneration
No full textLAUREA MAGISTRALELe malattie respiratorie gravano sui costi della sanità in tutto il mondo. Quasi 25 milioni di pazienti soffrono di malattie polmonari croniche allo stadio terminale solo negli Stati Uniti e di questi circa 400 000 muoiono ogni anno. In questo lavoro di tesi ci siamo focalizzati su due diverse malattie polmonari: la sindrome da distress respiratorio (ARDS, Acute Respiratory Distress Syndrome) e una mutazione genetica delle cellule alveolare di tipo II (ATII, Alveolar type II cells). L'area più colpita del polmone in queste malattie è l’alveolo e, più in particolare, l'epitelio alveolare.
ARDS è una forma di lesione polmonare acuta, classificata come malattia infiammatoria, in cui i polmoni sono collassati o presentano edema. Molti pazienti con ARDS sviluppano, superata la fase acuta, uno stato grave di fibrosi polmonare. Inoltre, quando le cellule ATII sono geneticamente danneggiate, gli alveoli non possono funzionare correttamente e non garantiscono gli scambi gassosi, non supportando il fabbisogno di ossigeno dell’organismo e causando sintomi patologici respiratori.
Attualmente, non vi sono terapie in grado di migliorare le conseguenze di queste malattie ed il trapianto di polmone, l'unico trattamento definitivo per questi pazienti, rimane ostacolato dalla carenza di organi donatori, dal possibile rigetto e dalla necessità di terapia immunosoppressiva.
L'obiettivo finale di questa tesi è stato quello di trovare nuovi approcci terapeutici, in grado di rimuovere solo le cellule epiteliali lesionate o difettose, preservando tutte le altre componenti polmonari e l'architettura circostante, al fine di riparare il tessuto e favorire la rigenerazione polmonare.
1. De-epitelializzazione in vivo di un modello di ratto in cui viene indotta l’ARDS. Dopo aver dimostrato di sia di poter indurre la malattia in vivo e che di poter trattare efficientemente con la de-epitelializzazione animali sani, la soluzione a base di CHAPS per rimuovere l'epitelio è stata utilizzata su ratti malati di ARDS, mantenendo intatta la rete vascolare e l'architettura polmonare, per stimolare e reclutare i progenitori polmonari per ripopolare l'organo trattato.
1. Targetizzazione specifica di pneumociti di tipo 2 affetti da modifiche genetiche. Il nostro nuovo farmaco, una proteina bioingegnerizzata composta dall’unione di una sostanza prodotta naturalmente nel polmone con il dominio catalitico di una tossina, che induce l'apoptosi cellulare, è stato testato in vitro e in vivo su topi al fine di rimuovere solo le cellule difettose e creare un ambiente favorevole per il trapianto di cellule esogene sane e la rigenerazione polmonare.Respiratory disease causes an immense worldwide health burden. Nearly 25 million people suffer from end-stage lung disease in the United States alone, with a staggering ~400,000 patients dying each year. We focused on two different lung diseases: acute respiratory distress syndrome (ARDS) and a genetic mutation in alveolar type II (ATII) cells. The most affected area of the lung in these diseases is the air sacs (alveoli) and, more in specific, the epithelium.
ARDS is clinically defined by severe lung damage with inflammation, and dysfunctional lungs that are collapsed or filled with fluid. Many ARDS survivors develop lung fibrosis and end-stage lung disease. On the other hand, when ATII cells are injured or diseased, the alveoli cannot function properly and therefore they cannot deliver sufficient oxygen to the bloodstream or remove carbon dioxide, causing respiratory symptoms.
At this time, ameliorating the consequences of these diseases remains challenging and lung transplantation, the only definitive treatment for these patients, remains hampered by donor organ shortages, long-term rejection, and the need for immunosuppressive therapy.
Final aim of this thesis work has been to find new therapeutic approaches, able to remove only the injured or defective epithelial cells, while preserving all the surrounding lung cells and architecture, in order to repair lung tissue and foster lung regeneration.
1) In vivo de-epithelialization in a rat model of ARDS. After having established an ARDS model in vivo and the feasibility and efficiency of the de-epithelialization treatment in healthy animals, CHAPS-based solution was used in order to remove the injured epithelium in the ARDS animal, maintaining the vasculature and the lung architecture intact, and to stimulate and recruit lung progenitors to repopulate the treated organ.
2) Targeted therapy for defective ATII cells disease. Our novel drug, a bioengineered therapeutic protein that joins a substance naturally produced by the lung together with the catalytic domain a toxin, that induces cell apoptosis, has been tested in vitro and in vivo on mice in order to remove only the defective cells and create a favorable environment for cells transplantation and lung regeneration
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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