1,720,961 research outputs found

    Nanoproteomics. Interaction of gold nanoparticles with proteins

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    Specific and reliable protein sensing and detection is a challenge of increasing interest due to their role as biomarkers in many diseases. Classical proteomics require time-consuming separation techniques and lacks the capability to assess protein activity variations uncorrelated to expression levels. Activity-based protein profiling (ABPP) is a strategy in which chemical probes (irreversible protein inhibitors) are covalently bound to target proteins with a shared activity and some signal arising from the probe is quantified, being sensitive to protein activity due to the binding step. Nonetheless, protein separation is still expensive in terms of time or requires the use of high-cost instrumentation. Our proposal was to employ gold nanoparticles as a tool for covalently capturing proteins of interest and separating them with ease from the remaining proteome by size-differentiation. Mixed monolayer nanoparticles have been obtained by two different methods, by direct substitution on an homogeneous monolayer or by supramolecular click-coupling reactions onto azido-functionalized derivatives. The two strategies were shown to be complementary; thiol exchange is simpler but substitution yields are difficult to predict when new thiols are tested whereas reliable click-coupling onto pre-substituted azido-nanoparticles requires the use of dibenzocyclooctyne derivatives to obtain high yields. We have developed and fully characterized supramolecular conjugates of gold nanoparticles with a thiol-based mixed-monolayer that endow the nanoparticles with high water solubility but also the capability to expose the targeting moiety on their surface. Avidin-biotin interaction has been chosen as model system to prove the capability of functionalized nanoparticles to effectively reach protein active sites and displace small molecules from their binding site in competition assays. On the other hand, supramolecular architectures based on chain-like arrays of nanoparticles have been prepared and shown to fuse in water to form nanorods or nanowires by treatment with glucosamine phosphate. Addition of thiol during the incubation stop nanoparticle fusion, opening the possibilities for a potential synthetic method to obtain anisotropic systems for NIR sensing.Rilevare e riconoscere proteine in modo specifico ed affidabile costituisce una sfida di crescente interesse a causa del ruolo che esse hanno come marcatori in molte malattie. La proteomica classica richiede tecniche di separazione assai dispendiose in termini di tempo e manca della capacità di correlare le variazioni di attività delle proteine che non siano legate ai loro livelli di espressione. L’identificazione di proteine sulla base della loro attività (activity-based protein profiling, ABPP) è una strategia in cui una specifica molecola (tipicamente un inibitore irreversibile della proteina) viene coniugata mediante un legame covalente alle proteine bersaglio caratterizzate da attività simile. Mediante un ‘reporter’, quale ad esempio un gruppo fluorescente, è possibile seguire il processo di coniugazione e rilevare la presenza delle proteine . Tuttavia, la separazione delle proteine coniugate dal resto del proteoma è ancora costosa sia in termini di che strumentali. La mia proposta era di impiegare nanoparticelle di oro come strumenti per catturare in modo covalente proteine di interesse separandole poi con facilità dal proteoma in ragione della loro diversa dimensione. Ho ottenuto nanoparticelle di oro passivate da un monostrato a composizione mista mediante due approcci sintetici diversi, rispettivamente mediante sostituzione diretta su un monostrato omogeneo o mediante reazioni di coniugazione utilizzando cicloaddizioni tipo’click’ sul sistema supramolecolare sfruttando derivati azido-funzionalizzati. Le due strategie hanno dimostrato di essere complementari. Lo scambio di tioli è più semplice, ma il grado di scambio è difficile da prevedere quando si usano nuovi tioli. Al contrario le reazioni di cicloaddizione ‘tipo click’ sono affidabili quando si usano derivati del dibenzocicloottino, ma richiedono una pre-funzionalizzazione del monostarto della nanoparticella. Ho sintetizzato e completamente caratterizzato sistemi supramolecolari costituiti da nanoparticelle di oro con monostrato misto ancorato sulla superficie dell’oro mediante un gruppo tiolico e dotate non solo di elevata solubilità in acqua, ma anche della capacità di esporre la porzione di targeting sulla loro superficie. Ho scelto l’interazione avidina-biotina come sistema modello per verificare la capacità delle nanoparticelle funzionalizzate di raggiungere in modo efficace il sito attivo di una proteina e di spostare eventuali substrati presenti nel loro sito di riconoscimento. In fine, ho realizzato architetture supramolecolari basate su array concatenati di nanoparticelle e ho dimostrato che essi sono in grado di fondersi tra di loro in acqua per formare nanotubi o nanofili in seguito al trattamento con glucosamina fosfato. L'aggiunta di tiolo, stabilizzando la struttura che si è formata durante la fusione delle nanoparticelle, previene l’ulteriore crescita, aprendo la possibilità ottenere sistemi anisotropi con caratteristiche spettroscopiche molto interessanti e potenzialmente sfruttabili per ‘sensing’ nel vicino IR (NIR)

    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
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