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    Correlazione tra saggi osteogenici ex vivo ed in vivo nel controllo di qualità di cellule staminali mesenchimali da midollo osseo “cGMP grade” destinate ad uso clinico

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    Tra i diversi approcci di medicina rigenerativa, c’è un crescente interesse riguardo all’utilizzo di cellule staminali mesenchimali (CSM) umane autologhe per aumentare la riparazione del tessuto osseo. Facendo parte di un consorzio europeo per la rigenerazione ossea, ci siamo occupati di valutare il potenziale osteogenico di cellule primarie di midollo osseo (MO) umano, isolate ed espanse in vitro secondo criteri “current grade manufacturing procedure” (CSM-MO-cGMP). In tale contesto, il nostro fine è stato quello di standardizzare un approccio funzionale che fosse rapido, riproducibile e facilmente applicabile. In letteratura numerosi geni sono stati associati alla cascata delle modificazioni geniche necessarie per il differenziamento osteogenico. Attraverso l’espressione di questi geni nelle CSM differenziate ex vivo raramente si riesce a predire la formazione dell’osso in vivo, ma recenti studi su CSM immortalizzate hanno individuato alcune correlazioni. Il nostro fine era comprendere se tali cambiamenti dell’espressione genica fossero applicabili anche in contesti differenti: (1) utilizzando CSM primarie; (2) impiegando un terreno di coltura addizionato di lisato piastrinico (LP) al posto del siero fetale bovino (SFB) e (3) applicando tali marker genici dopo il differenziamento osteogenico in vitro in 1 settimana anziché in 2. Sono stati testati 6 campioni di CSM-MO-cGMP indotti in senso osseo per valutare la mineralizzazione della matrice ex vivo. Di questi, quattro campioni sono risultati positivi per la colorazione Alizarin Red S (ALZ) e tre positivi per la colorazione di Von Kossa (VK). Dall’analisi istologica del trapianto in vivo per 6 settimane delle CSM-MO-cGMP in topi immunocompromessi è emerso che in quattro casi si è generata un’area di neoformazione ossea superiore al 15% dell’area totale della sezione. In particolare, il fenotipo della mineralizzazione della matrice ex vivo dopo due settimane di induzione ossea correla con la formazione in vivo di osso solo nel 50% dei campioni. Abbiamo testato un pannello di 12 geni considerati marcatori osteogenetici e dopo una settimana di induzione in vitro in senso osseo, sono stati identificati un gruppo di geni con una variazione statisticamente significativa nei livelli di espressione correlati con la mineralizzazione ex vivo. Non sono state rilevate correlazioni dirette tra l’espressione di singoli geni e la formazione di osso. Tuttavia, considerando l’analisi dei gruppi di 5 geni più espressi, siamo riusciti ad individuare i due donatori di CSM con la minor potenzialità di formare tessuto osseo in vivo, suggerendo il possibile utilizzo di tale approccio a supporto della sperimentazione clinica.Among diverse approaches in translational medicine, there is growing interest in use of autologous mesenchymal stem cells (hMSC) to enhance bone regeneration. Working within a European consortium, we aimed to evaluate the osteogenic potency of primary bone marrow- (BM) hMSC cultures isolated and expanded by clinical grade procedures (cGMP-BM-hMSC). Conforming to this context, we aimed to standardize a functional assay that was rapid, reproducible and readily applicable. Historically, numerous genes have been associated with the cascade of genetic changes required for osteogenic differentiation. Though expression of these genes in differentiated hMSC ex vivo rarely predict in vivo bone formation, recent studies using immortalized hMSC, have shown some correlations. We wished to explore whether such gene expression changes could also be applicable in different contexts: (1) using primary hMSC; (2) with growth medium supplemented by platelet lysate (PL) instead of fetal bovine serum (FBS) and (3) at 1 week instead of 2 weeks time points. Testing six cGMP-BM-hMSC samples for osteogenesis by ex vivo cellular matrix mineralization stainings, only four were positive for alizarin Red S (ALZ) and only three for Von Kossa (VK). Four of these donors generated ≥15% new bone area in histological sections from bone formation assays in immunodeficient mice after 6 weeks. Notably, the ex vivo phenotype of matrix mineralization staining at two weeks only correlated well with in vivo bone formation in 50% of the samples. When testing a panel of twelve osteogenic biomarker genes after one week of osteogenic induction, a subset of genes showed statistically significant changes in expression level that correlated with ex vivo mineralization. No direct correlation between expression and bone formation was found for any individual gene. Nonetheless, cluster analyses among five consistently expressed genes distinguished the two donors with least bone forming potential, suggesting this approach may prove helpful for clinical trials

    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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