1,720,979 research outputs found
Colorectal carcinogenesis: molecular and immunological events in a preclinical model
Full text linkIl cancro colorettale (CRC) è il secondo tumore più diffuso nei paesi industrializzati. L’insorgenza del CRC potrebbe essere diminuita interferendo con il processo carcinogenetico stesso, che inizia con una crescita incontrollata delle cellule trasformate, continua con la formazione di un polipo adenomatoso con o senza displasia e, successivamente, evolve in una neoplasia maligna. L’utilizzo di un modello animale preclinico in grado di riprodurre la stessa progressione della carcinogenesi umana, diventa quindi molto importante poiché permetterebbe di studiare gli eventi molecolari associati ad ogni step di evoluzione neoplastica. Il modello animale preclinico di CRC nei ratti BDIX messo a punto in questo lavoro, ha riprodotto tutti gli stadi della carcinogenesi osservati nell’uomo: la malattia infiammatoria dell’intestino, l’adenoma precoce e tardivo, il carcinoma in situ e quello avanzato. L’analisi immunoistochimica delle modificazioni di varie proteine coinvolte nel pathway di Wnt/β-catenina (β-catenina, E-caderina, APC, GSK3β, C-myc e Ciclina-D1) e K-ras, ha mostrato un’espressione e localizzazione molto simile nei tessuti umani e animali. Questi risultati confermano la validità del modello che è quindi utilizzabile per sviluppare nuove strategie preventive e/o terapeutiche. Inoltre, data l’immunocompetenza dei ratti BDIX, il modello può essere usato anche per analizzare le relazioni immunitarie tra il tumore e l’organismo, in particolare il meccanismo attraverso cui le cellule neoplastiche sfuggono all’immunosorveglianza. CRC può infatti evitare la risposta immune anche se l’organismo ospite ha un sistema immunitario in grado di reagire contro le singole cellule maligne o l’intero tumore. Nella lesione neoplastica si infiltrano diverse cellule del sistema immunitario, ma le più rappresentative sono i linfociti T, classificati in due sottogruppi. I Linfociti-T Infiltranti il Tumore (TIL, CD8+LAMP1+) sono i reali effettori della risposta immunitaria, in quanto hanno la capacità di eliminare le cellule anormali riconosciute. I linfociti-T regolatorie (T-reg CD4+CD25+FoxP3+) hanno importanti funzioni nel controllo o nell’inibizione della risposta immunitaria. Il tumore in crescita però, può evadere o sfruttare questi meccanismi a proprio vantaggio. Durante la progressione tumorale, le T-Reg sono correlate in maniera inversamente proporzionale alla presenza dei TIL; i TIL sono presenti negli stadi precoci ma diminuiscono drasticamente in quelli avanzati, suggerendo di non essere in grado di eradicare il tumore formato. Al contrario, le T-reg diventano elevate soltanto negli stadi avanzati, indicando indirettamente un loro coinvolgimento nell’immunopatogenesi del cancro. In questo caso è stato studiato il bilancio tra le due classi di linfociti T: la presenza e la distribuzione delle T-reg e dei TIL intorno alle lesioni neoplastiche riflettono consistentemente quanto osservato nella carcinogenesi umana. Questi risultati confermano che il modello può essere utilizzato per studi immunologici, ad esempio per mettere a punto nuovi protocolli di immunoterapia contro il cancro.
Nel lavoro è stato utilizzato un’innovativa tecnica fosfo-proteomica per studiare contemporaneamente lo stato di attivazione di diversi pathway coinvolti nel ciclo cellulare, nella sopravvivenza cellulare o nell’apoptosi, nella proliferazione o nell’invasione, in ciascuno stadio della carcinogenesi. Infatti, la Reverse Phase Protein Microarrays (RPPAs) associata alla Laser Capture Microdissection (LCM), consente l’analisi delle modificazioni post-traduzionali ed in particolare della fosforilazione; quest’ultima mette in evidenza le cascate di attivazione/disattivazione dei diversi pathway nei vari tessuti. I risultati preliminari ottenuti sono molto promettenti in quanto mostrano una clusterizzazione degli stadi precoci da quelli tardivi delle lesioni tumorali; è stato anche osservato il cambiamento statisticamente significativo di alcune proteine in relazione alla progressione tumorale. L’RPPA quindi, consente di generare una mappa di signaling cellulare per ogni singolo paziente, che può essere sfruttata per disegnare farmaci target-specifici all’interno di protocolli di terapia individualizzata o combinata.Colorectal cancer (CRC) is the second most common cancer in developed countries. CRC could be escapable by interfering with the process of carcinogenesis that begins with an uncontrolled growth in the initiated cryptal cells, continues with the formation of an adenomatous polyp with or without dysplasia and, eventually, evolves into epithelial malignancy. The use of pre-clinical animal models mimicking the human carcinogenesis process became very significant because, understanding the molecular events associated to each tumoural steps, it could be possible to develop early therapeutic intervention. The preclinical animal model of CRC in BDIX rats set up in this work, developed all the carcinogenesis steps observed in human: inflammatory bowel disease, early and late adenoma, carcinoma in situ and advanced carcinoma. The immunohistochemical study of modification of various proteins implicated in the Wnt/β-catenin pathway (β-catenin, E-cadherin, APC, GSK3β, C-myc and Cyclin-D1) and K-ras showed a very similar expression and localization between human and animal tissues. The results obtained, confirmed the validity of our pre-clinical model for studying the CRC carcinogenetic process, and for developing new preventive or therapeutic strategies. Furthermore, because of the immune-competence of our experimental model, it could be useful for studying the relationships between tumour and the host immune-response as well as the mechanisms by which cancer cells escape immune-surveillance. CRC can escape the host immune-response also if the organism has an immune system able to react against the malignant cell or the whole tumour. In the tumour are infiltrating several immune-cells, but the most representative type is the T-lymphocyte, classified in two subsets. The Tumour-Infiltrating T-Lymphocytes (TIL, CD8+LAMP1+) are the true “effectors” of immune response, because they have the ability to destroy the recognized abnormal cell. The Regulatory T-lymphocytes (T-reg CD4+CD25+FoxP3+) have important functions in order to control and/or inhibit the immune response when it isn’t necessary. The developing neoplasm can exploit and modify these mechanisms to own advantage. In effect, during the tumour progression T-reg are correlated in inverse proportion with the presence of TIL; TIL are more prominent in the early stages and decrease in the advanced stages of tumour, suggesting they are not able to eradicate a formed tumour. T-reg became most important just in the advanced stages: this is an indirect evidence that T-reg are involved in the immune-pathogenesis of cancer. In this work, we studied the balance between the two class of T-lymphocytes. We observed that the presence and distribution of T-reg and TIL around the neoplastic lesions reflect very well the equilibrium changes correlating to timing carcinogenesis observed in human CRC. These results indicate that our preclinical animal model is also suitable for immune-response studies, in particular to set up new protocols of tumor immunotherapy.
Moreover, in this work we utilized a innovative proteomic approach to study simultaneously the activation state of several pathways involved in cell cycle, cell survival or apoptosis, proliferation and invasion in each different stage of carcinogenesis. A new phospho-proteomic technology, Reverse Phase Protein Microarrays (RPPAs) associated to Laser Capture Microdissection (LCM) permit the study of some post-translational modifications, specifically the phosphorylation that explain the functional cellular defects and elucidate the working state of cellular signal pathways. The obtained results are very promising because they showed a clusterization between early and late stages of tumoural lesions and some significant end point were individuated changing in a time depending manner. RPPAs provide the opportunity to generate a protein network map of known cell signaling or pathways for an individual patient that may serve as drug target for individualized or combinatorial therapy
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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