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Studies of protein folding and misfolding on the ribosome
Get PDFProtein folding is one of the most important processes for maintaining cellular homeostasis. It begins co-translationally on the ribosome, however, it also competes with protein misfolding. Under severe conditions, protein misfolding can result in the accumulation of toxic aggregates, which are known to give rise to lethal conformational diseases including those linked to neurodegeneration, respiratory diseases, diabetes, and cancer. Very little is understood of co-translational protein misfolding mechanisms as they first begin in the cell, and also of their links to human disease. Alpha-1 deficiency, for example, results from pathological variants of the alpha-1-antitrypsin (AAT) protein, forming toxic polymer aggregates in the endoplasmic reticulum in hepatocytes, where the protein is synthesised.
To investigate aspects of co-translational misfolding, this Thesis examines the biosynthesis of AAT and of a pathological disease variant (Z AAT), on the ribosome, in a mammalian cell-free system, by applying quantitative biochemistry and structural biology techniques. These studies have revealed that ribosome-bound AAT nascent chains (NCs) form co-translational folding intermediates which are important for guiding correct folding (Chapter 3). Also observed are novel circumstances under which this process is hindered, as indicated by the presence of naturally-paused ribosomes at the full-length of AAT sequence; these induce ribosome collisions and the formation of higher-order ribosome-associated assemblies (Chapter 4), which are evident in biochemical assays and visualised using negative stain electron microscopy. The formation of ribosome-bound mis-assemblies, as investigated using sucrose density gradients and quantitative biochemistry, reveals that both “co-post” and “co-co” mechanisms are possible for the formation of AAT polymers (Chapter 5). Finally, a high-resolution cryo-EM structure of the AAT ribosome nascent chain complex (RNC), gives insights into the NC-ribosome interactions that could contribute to its natural stalling (Chapter 6).
A better understanding of the origins of the AAT toxic aggregates that lead to disease, will provide a foundation for therapeutics centred on early-intervention strategies
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Get PDF“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
Get PDFWe 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
Investigation of parents’ knowledge focusing on children’s dermatological disorders regarding the use of biological versus chemicals products
No full textOBJECTIVEThe purpose of this study is to investigate the parents’ knowledge focusing on children’s dermatological disorders regarding the use of biological versus chemicals productsMETHODSThe current study took place from end of January 2014 to end of April 2014 in one pedo-dermatological and one pediatric in the Attica region.The study population was 200 children, 103 boys and 97 girls, age 0-5 years suffering from various types of dermatological disorders.The parents of each child completed a questionnaire assessing the clinical status of the child, the therapeutic approach adopted and the information concerning the economic and social approach of the patient's family.The data coding and the use of the statistical package IBM SPSS version 20 allowed the further configuration and statistical analysis of the findings.The appearance of dermatological disorders occurs in 50 % of the patients at the age of 0-7 months and in 50 % at the age of 8-60 months. The most frequent type of dermatitis in 80% of the patients was the atopic dermatitis. Symptoms of mild nature occurred in the majority of dermatitis. Atopic dermatitis reaches the largest percentage of acute and chronic dermatological disorders.The use of chemicals products like the corticosteroids is used to treat the symptoms of dermatitis. According to parents’ reply, the improvement based on the cortisone usage is valuable and at most considerable.Statistically significant correlation was found between the use of chemical products and the monthly cost of the treatment. Non chemical corticosteroids are mainly used as conservative - second line therapy. A percentage of 3.4 % of the patients presented an allergic reaction after the implementation of chemical corticosteroids and a rate of 27.3% showed irritation and itchiness after the application of non-chemical corticosteroids.The treatment of dermatitis, apart from the use of chemical products, is complemented with the use of other alternative methods, such as the use of biological products. 76.5 % of the patients seem to use biological products for topical use.A 40.10% of the sample suggested that biological products for topical use seams to have a considerable reduction on dermatitis exacerbation with their replies. There is also correlation between the use and the degree of biological products use with the level of parents’ awareness for biological products. Statistically significant correlation exists between the parents’ level of education with the use of biological products. No adverse reactions of biological products are recorded.CONCLUSIONBiological products for topical use seam to have a considerable reduction on dermatitis exacerbation.ΣΚΟΠΟΣΟ σκοπός της παρούσας μελέτης είναι η διερεύνηση των γνώσεων γονέων παιδιών με δερματοπάθειες για χρήση βιολογικών προϊόντων σε σύγκριση με χημικά προϊόντα.ΥΛΙΚΟ-ΜΕΘΟΔΟΣΗ παρούσα μελέτη πραγματοποιήθηκε το χρονικό διάστημα από τέλος Ιανουαρίου 2014 έως τέλος Απριλίου 2014 σε ένα παιδοδερματολογικό και ένα παιδιατρικό ιατρείο στην περιοχή της Αττικής.Τον μελετώμενο πληθυσμό αποτέλεσαν 200 παιδιά, 103 αγόρια και 97 κορίτσια, ηλικίας 0-5 ετών που έπασχαν από διάφορα είδη δερματοπάθειας. Συμπληρώθηκε ειδικό ερωτηματολόγιο από τους γονείς των ασθενών.Η συλλογή στοιχείων έγινε με τη συμπλήρωση ερωτηματολογίων.Η στατιστική επεξεργασία των στοιχείων έγινε με τη χρήση του στατιστικού πακέτου SPSS V.20.ΑΠΟΤΕΛΕΣΜΑΤΑΗ εμφάνιση της δερματοπάθειας παρουσιάζεται στο 50% των ασθενών σε ηλικία 0-7 μηνών και στο υπόλοιπο 50% σε ηλικία 8-60 μηνών. Ο πιο συχνός τύπος δερματίτιδας σε ποσοστό 80% ήταν η ατοπική δερματίτιδα. Όλες οι δερματοπάθειες στο μεγαλύτερο ποσοστό τους είναι ήπιας μορφής. Το μεγαλύτερο ποσοστό της οξείας αλλά και της χρόνιας δερματοπάθειας κατείχε η ατοπική δερματίτιδα.Η αντιμετώπιση των συμπτωμάτων της δερματοπάθειας γίνεται με τη χρήση χημικών σκευασμάτων,των κορτικοστεροειδών. Σύμφωνα με την εκτίμηση των γονέων, η βελτίωση που παρουσιάζεται στους ασθενείς κατά τη χρήση της κορτιζόνης είναι μεγάλη. Ένα ποσοστό 3,4% παρουσίασε αλλεργική αντίδραση μετά την εφαρμογή των χημικών κορτικοστεροειδών. Τα ανοσοτροποποιητικά χρησιμοποιούνται από το μεγαλύτερο ποσοστό των ασθενών ως θεραπεία συντήρησης. Ένα ποσοστό 27,3% παρουσίασε ερεθισμό και κνησμό μετά την εφαρμογή των χημικών μη κορτικοστεροειδών.Η αντιμετώπιση της δερματοπάθειας, πέραν της χρήσης των χημικών σκευασμάτων, γίνεται και με τη χρήση άλλων εναλλακτικών μεθόδων όπως η χρήση των βιολογικών προϊόντων. Οι ασθενείς του δείγματος δείχνουν να χρησιμοποιούν τα βιολογικά προϊόντα τοπικής χρήσης σε ποσοστό 76,5% και τα πόσιμα σε ποσοστό 18%. Από τη μελέτη προκύπτει ότι τα βιολογικά προϊόντα τοπικής χρήσης επιδρούν στη μείωση της έξαρσης της δερματοπάθειας. Το 40,10% των γονέων εκτιμάει ότι η χρήση των βιολογικών προϊόντων τοπικής χρήσης φαίνεται να μειώνει αρκετά την έξαρση των δερματοπαθειών.Υπάρχει επίσης στατιστικά σημαντική συσχέτιση μεταξύ της χρήσης και του βαθμού χρήσης των βιολογικών προϊόντων με τον βαθμό ενημέρωσης των γονέων για τα βιολογικά προϊόντα. Τέλος προκύπτει στατιστικά σημαντική συσχέτιση του επιπέδου εκπαίδευσης του γονέα με την χρήση βιολογικών προϊόντων. Ανεπιθύμητες ενέργειες των βιολογικών προϊόντων δεν καταγράφηκαν από τους γονείς των ασθενών του δείγματος.ΣΥΜΠΕΡΑΣΜΑΤΑΤα βιολογικά προϊόντα τοπικής χρήσης χρησιμοποιούνταν περισσότερο σε σύγκριση με τα πόσιμα βιολογικά προϊόντα. Τα βιολογικά προϊόντα τοπικής χρήσης επιδρούν στη μείωση της έξαρσης της δερματοπάθεια
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe 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
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