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    Proteomica e metabolomica: nuove piattaforme tecnologiche per applicazioni in campo biologico

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    Dottorato di ricerca in Genetica e biologia cellulareThe word „omics‟, is derived from the Greek suffix, „ome‟ (meaning all, every). In the mid 1990‟s, rapid evolution and growing knowledge concerning genomes led to a quick development of the full range of „omics‟ approaches (genomics, transcriptomics, proteomics, metabolomics). This PhD thesis focuses on the application of new “omics” sciences to characterized samples of biomedical interest such as pharmaceutical products. The first section is focused on the characterization of important pharmaceutical products used by hemophiliac patients, trough proteomics approaches. The first objective of this study was to compare the heterogeneity and the high purity of three rFVIII commercially available rFVIII concentrates before and after thrombin digestion. The second object was to extend the same study to plasma derived factor VIII . The second part of my PhD project was designed mainly to the development and optimization of a new HPLC-MS method for metabolomics. In the last part of my research I used this analytical approach to investigate metabolites in blastocoels fluid that is a routine waste product prior to pre-implantation blastocyst vitrification. The aim of this study was directed to identify a correlation between quali-quantitative profiles of small molecules of metabolic interest and the outcome of embryo transfer through a simple HPLC-MS assay. The last part of my research was dedicated to studing metabolism in red blood cell during storage. Proteome and metabolomic approaches, are widely used for studies complex biological systems and can be used for applications in biological areas.La parola omica deriva dal suffisso greco “ome” che significa: tutto, intero, completo. In particolar modo per quanto riguarda l’area biologica lo scopo delle scienze omiche è quello di avere una visione globale per comprendere la vita e la sua organizzazione. L’evoluzione rapida e la crescita di conoscenza riguardante il genoma hanno portato ad una rapida crescita nello sviluppo di nuove scienze (genomica, trascrittomica, proteomica, metabolomica) La mia tesi di dottorato riguarda le applicazioni delle nuove scienze omiche per caratterizzare campioni di interesse biomedico come ad esempio prodotti farmaceutici. Il primo obiettivo dello studio è stato quello di comparare e caratterizzare fattore VIII ricombinante prodotto da tre ditte farmaceutiche differenti. Questi prodotti attaualmente utilizzati per curare l’emofilia sono stati studiati prima e dopo attivazione attraverso il taglio effettuato dalla trombina. Il secondo obiettivo della mia tesi è stato quello di estendere lo studio proteomico non solo ai fattori VIII ricombinanti ma anche a quelli plasmaderivati. La seconda parte del mio progetto è stata dedicata allo sviluppo e all’ottimizzazione di un nuovo metodo basato sull’utilizzo di HPLC e spettrometro di massa per lo studio della metabolomica. Nell’ultima parte della mia tesi ho utilizzato questo tipo di approcio per studiare la variazione metabolica all’interno del fluido del blastocele. Lo scopo di questo lavoro è stato quello di individuare marker metabolici che possano definire la qualità delle blastocisti da impiantare durante il processo della FIVET. Infine ho utilizzato questo metodo per mettere in evidenza la variazione metabolica nei globuli rossi durante la loro conservazione in sacca

    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

    Urinary Untargeted Metabolic Profile Differentiates Children with Autism from Their Unaffected Siblings

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    Autism Spectrum Disorder (ASD) encompasses a clinical spectrum of neurodevelopmental conditions that display significant heterogeneity in etiology, symptomatology, and severity. We previously compared 30 young children with idiopathic ASD and 30 unrelated typically-developing controls, detecting an imbalance in several compounds belonging mainly to the metabolism of purines, tryptophan and other amino acids, as well as compounds derived from the intestinal flora, and reduced levels of vitamins B6, B12 and folic acid. The present study describes significant urinary metabolomic differences within 14 pairs, including one child with idiopathic ASD and his/her typically-developing sibling, tightly matched by sex and age to minimize confounding factors, allowing a more reliable identification of the metabolic fingerprint related to ASD. By using a highly sensitive, accurate and unbiased approach, suitable for ensuring broad metabolite detection coverage on human urine, and by applying multivariate statistical analysis, we largely replicate our previous results, demonstrating a significant perturbation of the purine and tryptophan pathways, and further highlight abnormalities in the “phenylalanine, tyrosine and tryptophan” pathway, essentially involving increased phenylalanine and decreased tyrosine levels, as well as enhanced concentrations of bacterial degradation products, including phenylpyruvic acid, phenylacetic acid and 4-ethylphenyl-sulfate. The outcome of these within-family contrasts consolidates and extends our previous results obtained from unrelated individuals, adding further evidence that these metabolic imbalances may be linked to ASD rather than to environmental differences between cases and controls. It further underscores the excess of some gut microbiota-derived compounds in ASD, which could have diagnostic value in a network model differentiating the metabolome of autistic and unaffected siblings. Finally, it points toward the existence of a “metabolic autism spectrum” distributed as an endophenotype, with unaffected siblings possibly displaying a metabolic profile intermediate between their autistic siblings and unrelated typically-developing controls

    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
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