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Merkel cell polyomavirus, a small DNA tumour virus, in humans
No full textMerkel cell polyomavirus (MCPyV) which causes an almost ubiquitous, asymptomatic infection, rarely causes an aggressive skin tumor with limited therapeutic options, i.e., Merkel cell carcinoma (MCC). Despite serum anti-MCPyV IgGs have been detected with a relatively high prevalence in healthy individuals, previous studies reported variable rates. Innovative immunoassays are needed to determine the MCPyV serology in humans.
The main aim of the present thesis was to investigate the impact of oncogenic MCPyV infection in the healthy population. To this end, a new indirect ELISA assay using two synthetic peptides mimicking epitopes of MCPyV capsid proteins 1 and 2 (VP1/VP2) was developed and validated to analyze the presence of anti-MCPyV IgGs in sera from healthy individuals, including children (HC, 0-20 yrs), adults (HS, 21-65 yrs), and elderly (ES, 66-100 yrs).
Synthetic peptides were initially computationally designed to detect IgGs to MCPyV mimotopes. The assay performance in detecting anti-MCPyV IgGs was afterwards determined on MCPyV-positive/-negative control sera. The assay showed a high performance.
Then, the ELISA was extended to HC (n=344), HS (n=510) and ES (n=226) sera with unknown MCPyV serology. Age-/gender-specific MCPyV seroprevalences were examined. The overall prevalence of serum anti-MCPyV IgGs was 40.7% in HC. HC age stratification revealed a significantly lower MCPyV seroprevalence in the 0-5 yrs cohort (13%) compared with the older cohorts. MCPyV serological profile showed that the 0-5 yrs cohort had the lowest Optical densities (ODs) compared to the older cohorts. Higher ODs were found in females than males. The prevalence of anti-MCPyV IgMs was 29.7% in HC, with similar rates in age-stratified HC. The 0-5 yrs cohort had the lowest IgM ODs compared to the older cohorts. The 6-10/11-15 yrs cohorts had the highest ODs compared to the 16-20 yrs cohort. A higher seroprevalence of anti-MCPyV IgG and IgM were found in females than in males. The anti-MCPyV IgG and IgM reactivity patterns in HC were also simultaneously evaluated. IgG and IgM ODs showed an inverse trend, as being increased and decreased, respectively, in the older HC cohort. The prevalence of serum anti-MCPyV IgGs was 61.8% in HS group. Higher ODs were found in females than in males. MCPyV-seroprevalence of ES sera was 63.7%, a proportion higher than the 40.7% observed in HC, and similar to the 61.8% detected in the HS. MCPyV-serology was then examined in HC, HS, and ES, which were stratified in 5-yrs range cohorts. MCPyV seroprevalence was lower in the 0-5 yrs cohort (13%) than in the older cohorts (52.3-72%).
Moreover, the 0-5 yrs cohort had the lowest OD values. Higher ODs were found in 6-10, 11-15 and 16-20 yrs cohorts compared to the other cohorts.
The results of the present thesis indicate that the assay developed herein can efficiently detect serum anti-MCPyV IgGs. Our data indicate that MCPyV infection is widespread in humans. After seroconversion in pediatric age, MCPyV circulates asymptomatically in the prepuberal, adult and elder populations at a high prevalence, without substantial age-related variations in adulthood and senility.
New approaches for MCC treatment are needed. In the second phase of this thesis, the antineoplastic effects of ATRA and decitabine drugs were evaluated in vitro in MCC cell lines, to develop new antitumor therapies with clinical application.
The activities of the two drugs were assayed as single agents in MCC cell lines MCC13, MCC26, MKL-1 and Peta to verify their antiproliferative potential. The ATRA IC50-dose was 100 μM and 75 μM in MCC13 and Peta, respectively. ATRA showed no antiproliferative effects on MCC26. The decitabine IC50-dose was 0.5 μM in both MCC13 and MCC26, while it was 50 nM in MKL-1 cells.
Both ATRA and decitabine effectively reduced the proliferation of MCC cells in vitro. These preliminary results may improve the development of new approaches for MCC therapy.Il poliomavirus delle cellule di Merkel (MCPyV) causa un'infezione asintomatica nell’uomo. In rari casi, MCPyV induce un tumore cutaneo aggressivo con limitate opzioni terapeutiche, il carcinoma delle cellule di Merkel (CCM). Nonostante le IgG anti-MCPyV siano state rilevate con una prevalenza relativamente alta negli individui sani, dati precedenti indicano tassi di prevalenza variabili. Sono quindi necessari nuovi saggi immunologici per determinare la sierologia MCPyV nell’uomo.
Lo scopo di questa tesi era di indagare l'impatto dell'infezione da MCPyV nella popolazione sana. È stato dunque sviluppato e validato un nuovo test ELISA che impiega due peptidi sintetici che mimano gli epitopi delle proteine capsidiche di MCPyV (VP1/2) per valutare la presenza di IgG anti-MCPyV in sieri di soggetti sani, compresi bambini (HC, 0-20 anni), adulti (HS, 21-65 anni) e anziani (ES, 66-100 anni).
I peptidi sono stati disegnati in silico per rilevare le IgG verso MCPyV. Il test è stato valutato in termini di performance sui sieri di controllo MCPyV-positivi/-negativi, mostrando prestazioni elevate. L'ELISA è stato esteso a sieri HC (n=344), HS (n=510) ed ES (n=226) con una sierologia per MCPyV ignota.
La prevalenza delle IgG anti-MCPyV era del 40.7% negli HC. È stata inoltre valutata la prevalenza di MCPyV specifica per età/genere. La coorte 0-5 anni ha evidenziato una prevalenza di MCPyV più bassa rispetto alle altre coorti. Il profilo sierologico di MCPyV ha mostrato densità ottiche (OD) più basse nella coorte 0-5 anni rispetto alle altre coorti. OD più alte sono state trovate nelle femmine rispetto ai maschi.
La prevalenza delle IgM anti-MCPyV nel gruppo HC è risultata essere del 29.7%, con tassi simili negli HC stratificati per età. La coorte 0-5 anni aveva le OD più basse rispetto alle altre coorti. Le coorti 6-10/11-15 anni avevano OD più alte della coorte 16-20 anni.
Sono stati valutati simultaneamente i pattern sierici di IgG e IgM anti-MCPyV negli HC. Le OD di IgG e IgM hanno mostrato una tendenza inversa, con rispettivo aumento e diminuzione, nella coorte HC più adulta.
La prevalenza delle IgG sieriche di MCPyV era del 61.8% negli HS. Le femmine hanno mostrato OD più alte dei maschi. La prevalenza delle IgG anti-MCPyV negli ES era del 63.7%; una percentuale superiore al 40.7% degli HC e simile al 61.8% degli HS. La sierologia di MCPyV è stata anche studiata in HC, HS ed ES, stratificati in coorti di 5 anni. La prevalenza di MCPyV era inferiore nella coorte 0-5 anni (13%) rispetto alle altre coorti (52.3-72%). Inoltre, la coorte 0-5 anni aveva i valori di OD più bassi. OD più elevate sono state trovate nelle coorti 6-10/11-15/16-20 anni rispetto alle altre coorti.
I risultati di questa tesi indicano che l'ELISA indiretto qui sviluppato è affidabile nel rilevare IgG anti-MCPyV sieriche. I nostri dati immunologici rivelano che l'infezione da MCPyV è diffusa nell'uomo. Dopo la sieroconversione in età pediatrica, MCPyV circola senza sintomi nella popolazione prepuberale, adulta e anziana con un'elevata prevalenza, senza variazioni nell'età adulta e nella senilità.
Sono necessari nuovi approcci per il trattamento del CCM. In una seconda fase della tesi, gli effetti antineoplastici di ATRA e decitabina sono stati valutati in vitro in linee cellulari di CCM, per sviluppare nuove terapie antitumorali con applicazione clinica.
Le attività dei due farmaci sono state analizzate in linee cellulari MCC13, MCC26, MKL-1 e Peta per valutarne il potenziale antiproliferativo. La dose IC50 di ATRA era rispettivamente di 100 μM e 75 μM in MCC13 e Peta. ATRA non ha dato effetti sulle MCC26. La dose IC50 di decitabina era di 0.5 μM sia in MCC13 che in MCC26, mentre era di 50 nM nelle MKL-1. Sia ATRA che decitabina hanno ridotto la proliferazione delle cellule CCM in vitro. Questi risultati preliminari possono aprire la strada a nuovi approcci per la terapia CCM
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Full text link“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
Full text linkWe 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
Full text linkWe 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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