1,721,074 research outputs found

    From computational genomics to systems metabolomics for precision cancer medicine and drug discovery

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    Notwithstanding decades of scientific and clinical investigation, cancer remains a disease that endangers many lives and brings deep sorrow to many families. So far, the war on cancer has been technology-driven. First, recombinant DNA technologies have led to the identification of oncogenes and tumour suppressor genes. Next, genomic sequencing and transcriptome analysis have allowed the characterization of both the set of mutated oncogenes and the very complex and variable transcriptome expression profiles, which appear to characterize each different cancer cell, both in human cell lines and in clinical samples. Enormous amounts of omics data of various kinds have been collected and analyzed using refined analytical technologies, and stored and made available for retrieval in specialized databases. By connecting such data with information on which drugs have been used for each patient, characterized by the specific signature of the driver mutation and the omics profile, and on the treatment outcome, the scientific community is now generating the so-called Cancer Big Data. On these bases, genomic Big Data and their analysis by computer sciences are predicted to be the field in which the war on cancer will finally be wo

    SYNTHESIS OF CYCLIC BRANCHED OLIGODEOXYRIBONUCLEOTIDES

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    The cyclic branched oligodeoxyribonucleotides 7 and 8 have been prepared via the intermediate 4 synthesized using a phosphotriester approach

    6-Chloroxanthosine, a useful intermediate for the efficient syntheses of [6-15N]-isoguanosine, isoinosine and other purine nucleoside analogues

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    6-Chloroxanthosine 1, when activated towards nucleophilic displacement at the 6-C position by conversion into the corresponding 3-N-(2,4- dinitrophenyl) derivative 4, reacted with aq. 15NH3 to afford [6-15N]- isoguanosine 3b in 81% overall yield. Catalytic hydrogenation (Pd/C) of 1 led in 60 % yield to isoinosine 8; alternatively, this could be obtained in 88 % overall yield through alkaline hydrolysis of triphenylphosphonium salt 6, synthesized from 1 by reaction with PPh3. The reactivity of 1 was further explored by treating it with primary and secondary amines: the 6-N propylamino and the 6-N piperidinyl derivatives (5a and 5b, respectively) could thus both be prepared in more than 90 % yield

    MicroRNA come target terapeutici per il trattamento della fibrosi cistica

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    La Fibrosi Cistica (CF) è una malattia autosomica recessiva che si manifesta con un’incidenza di circa 1/3000 nati. E’ causata da mutazioni del gene codificante la proteina CFTR che causano la scomparsa o la riduzione dell’attività di canale del cloruro. E’ stato recentemente dimostrato il coinvolgimento di alcuni microRNA complementari al 3’UTR (UnTranslated Region) del trascritto del gene CFTR nella riduzione dell’espressione della proteina, causando la malattia o l’aggravarsi del suo fenotipo. I microRNA, inoltre, sembrano essere responsabili del mantenimento di bassi livelli di CFTR negli adulti. Pertanto, l’obiettivo principale del nostro lavoro è stato quello di utilizzare specifiche molecole, denominate miRNA Target Site Blocker (TSB), per impedire il legame dei microRNA al 3’UTR di CFTR, al fine di produrre più proteina ed aumentare, di conseguenza, il flusso netto di ioni cloruro attraverso la membrana plasmatica. Tale meccanismo potrebbe dunque rappresentare un nuovo approccio terapeutico per pazienti CF che, conservando un’attività minima residua del canale, possono ricevere un beneficio clinico dall’aumento netto del flusso di ioni cloruro

    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
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