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    EXPLORING THE ROLE OF NICOTINAMIDE N-METHYLTRANSFERASE ENZYME IN HUMAN OSTEOSARCOMA: POTENTIAL CONTRIBUTION TO PROLIFERATION, MIGRATION AND CHEMOSENSITIVITY

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    L'osteosarcoma (OS) è il tumore osseo maligno più comune nei bambini e nei giovani adulti, con un tasso di sopravvivenza a 5 anni che varia dal 70% al 20%, a seconda dello stadio della malattia. Si tratta di una neoplasia particolarmente aggressiva, spesso caratterizzata dalla presenza di metastasi polmonari già al momento della diagnosi. Inoltre, l’elevata resistenza ai trattamenti chemio- e radioterapici contribuisce in modo significativo alla prognosi sfavorevole. Queste caratteristiche sottolineano l'importanza di approfondire i meccanismi molecolari alla base della insorgenza di tale neoplasia, al fine di identificare nuovi bersagli terapeutici e sviluppare strategie di trattamento più efficaci. Il presente studio si è focalizzato sulla nicotinamide N-metiltrasferasi, un enzima citosolico che utilizza l’S-adenosil-L-metionina come donatore di metile per catalizzare la reazione N-metilazione della nicotinamide e dei suoi analoghi strutturali. Un’aumentata espressione di quest’ultimo è stata documentata in numerosi tumori solidi, dove sembra contribuire alla promozione della proliferazione, della capacità migratoria e della resistenza ai convenzionali trattamenti antineoplastici. L’espressione dell’NNMT è stata analizzata, dapprima a livello tissutale, mediante analisi immunoistochimica su campioni di tessuto osseo sano e di osteosarcoma fissati in formalina e inclusi in paraffina. Per studiare il contributo dell’enzima al metabolismo tumorale, le linee cellulari di osteosarcoma U-2 OS e Saos-2 sono state trasfettate con vettori plasmidici contenenti shRNA diretti contro la sequenza nucleotidica relativa al messaggero dell’NNMT. L’efficienza del silenziamento è stata verificata tramite Real-Time PCR e analisi Western blot. Successivamente, è stato valutato l’effetto del silenziamento dell’enzima sulla vitalità cellulare, proliferazione, capacità migratoria e sensibilità agli agenti chemioterapici, quali doxorubicina e cisplatino. I risultati hanno evidenziato livelli significativamente più elevati di espressione dell’NNMT nei tessuti tumorali rispetto ai campioni di osso sano. Inoltre, il silenziamento dell’NNMT nelle linee cellulari di OS ha determinato una significativa riduzione della vitalità, della proliferazione e della migrazione cellulare, oltre ad un aumento della chemiosensibilità. Questi dati suggeriscono che l’NNMT potrebbe rappresentare un affidabile biomarcatore per la diagnosi dell’osteosarcoma, oltre che un potenziale bersaglio per lo sviluppo di nuove ed efficaci strategie terapeutiche nei pazienti affetti da tale neoplasia.Osteosarcoma (OS) is the most common malignant bone tumor in children and young adults, with a 5-year survival rate ranging from 70% to 20%, depending on the disease stage. OS is an aggressive neoplasm, often characterized by the presence of lung metastases at diagnosis. Furthermore, its marked resistance to chemo- and radiotherapy significantly contributes to the poor prognosis. This highlights the urgent need to investigate the molecular mechanisms underlying OS tumorigenesis to identify novel therapeutic targets for more effective treatment strategies. In this study, we focused on the role of nicotinamide N-methyltransferase (NNMT), a cytosolic enzyme that uses S-adenosyl-L-methionine as a methyl donor, to catalyze the N-methylation of nicotinamide and related compounds. NNMT overexpression has been reported in several solid tumors, where it has been implicated in promoting cancer cell proliferation, migration, and resistance to therapeutic agents. NNMT expression was assessed by immunohistochemistry in formalin-fixed, paraffin-embedded OS and healthy bone tissue samples. To investigate the functional contribution of NNMT to tumor cell metabolism, U-2 OS and Saos-2 osteosarcoma cell lines were transfected with short hairpin RNA (shRNA) vectors targeting NNMT mRNA. The efficiency of NNMT knockdown was evaluated by Real-Time PCR and Western blot analyses. The impact of NNMT silencing on cell viability, proliferation, migration, and sensitivity to chemotherapeutic agents (doxorubicin and cisplatin) was subsequently determined. Our results revealed significantly higher NNMT expression levels in OS tissues compared to healthy bone samples. Moreover, NNMT silencing in OS cell lines led to a marked reduction in cell viability, proliferation, and migration, accompanied by enhanced sensitivity to chemotherapeutic treatments. These findings suggest that NNMT could represent a valuable biomarker for OS diagnosis and a potential target for developing effective therapeutic strategies for OS patients

    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

    Author Under Sail The Imagination of Jack London, 1893-1902

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    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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