1,720,959 research outputs found
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
Design, synthesis and biological evaluation of small molecules able to interact with macromolecular targets involved in tumor pathology
Full text link2019 - 2020Inflammation and cancer are two complex pathological processes that exploit several molecular actors. The identification of new platforms able to interfere with biological targets placed at the crossroads of these two pathways is strongly needed both, for the development of promising drug candidates, and as chemical probes useful to further investigate less understood biological aspects. Three main targets, involved at different levels in inflammation and cancer, have been thoroughly investigated: the Heat Shock Factor 1 (HSF1), the Bcl-2 associated athanogene 3 protein (BAG3), and the microsomal Prostaglandin E Synthase-1 (mPGES-1). The obtained results can be summarized in the three main sections reported below according to the target of interest:
a) Discovery of new potential modulators of HSF1 by computer-aided approach.
Heat shock factor 1 (HSF1) is the master regulator of the cytoprotective Heat Shock Response (HSR) in eukaryotes. The HSR is an evolutionarily conserved mechanism triggered by proteotoxic stress and involves the rapid and transient expression of Heat Shock Protein (HSP), molecular chaperones that restore cell proteostasis. HSF1 activity is amplified in many tumor contexts in a manner that resembles a chronic state of stress, characterized by high levels of hsp gene expression as well as HSF1-mediated non-hsp gene regulation. HSF1 and its gene targets are implicated in tumorigenesis as assessed in several experimental tumor models and facilitate metastatic and resistant properties within cancer cells. HSF1 is emerged as a therapeutic target valuable in cancer related disorders although, for several reasons, it can be considered quite “undruggable”. The workflow that guided us in the research of potential HSF1 binders was based on an integrated approach including computational studies, synthesis of the most promising molecules, biophysical assays, and in-cell assays. Starting from the HSF1-DBD crystallographic structure in complex with an HSE (PDB: 5D5U), two types of virtual screening were performed. The molecules with the best docking score values were purchased or synthesized and their affinity for the full-length protein was evaluated by SPR assay. These studies led us to identify several molecules potentially able to target the protein, in particular, we found that BD-1 and LAM17 are able to bind the full-length protein with a dissociation constant in the low micromolar range, and furthermore, basing on in-depth biological studies, they showed to regulate the transcriptional activity of HSF1.
b) Design, synthesis and biological evaluation of BAG3 modulators.
Bcl2-associated athanogene 3 (BAG3) protein is a member of the BAG family of co-chaperones that interacts with the ATPase domain of the Heat Shock Protein 70 (Hsp70) through the conserved BAG domain. BAG3 is the only member of the family to be induced by stressful stimuli, mainly through the activity of HSF1 on bag3 gene promoter. In addition to the BAG domain, BAG3 also contains a WW domain and a proline-rich (PXXP) repeat that mediate its binding to different partners. These multifaceted interactions underlie the BAG3 ability to modulate key biological processes like apoptosis, development, cytoskeleton organization, and autophagy, thereby mediating the cell adaptive responses to stressful stimuli. In normal cells, BAG3 is constitutively present in a very few cell types, including cardiomyocytes and skeletal muscle cells, in which the protein appears to contribute to cell resistance to mechanical stress. A growing body of evidence indicates that BAG3 is highly expressed in several tumor types where it is proven to sustain cell survival, resistance to therapy, motility, and metastatization. In some tumor types, the down-modulation of BAG3 levels was shown, as a proof-of-principle, to inhibit neoplastic cell growth in animal models. With the aim of exploring the BAG3 protein as cancer target, through a combined approach of structure-based drug design and biophysical methods, in 2017 the research group of which I am part
discovered the first selective BAG3 modulator featuring a 2,4-thiazolidinedione scaffold. Basing on these promises, I continued to explore the chemical space around the thiazolidinedione core, and, supported by computational studies, a new compounds collection has been developed. In order to assess the affinity for the target, these molecules were tested, through SPR assay, against both the full-length BAG3 protein and the BAG3-BD. LK6 proved to be the most promising molecule showing a high affinity for both the full protein (6.3 ± 0.3 μM) and the BAG domain (27.6 ± 1.9 μM). According with its favorable binding properties, LK6 showed a potent cytotoxicity and the ability to cause a cell accumulation in the G1 phase, suggesting an apoptosis/necrosis event which was confirmed by the significant dose-dependent reduction of caspase 3 and 9, the main effectors of the programming cell death, in treated cells.
c) Identification of mPGES-1 inhibitors through a multistep approach.
Microsomal prostaglandin E synthase-1 (mPGES-1) is the terminal synthase responsible for the production of prostaglandin E2 (PGE2). PGE2 is a bioactive lipid that can elicit a wide range of biological effects associated with inflammation and cancer. The pleiotropic role of PGE2 is mainly mediated by the activation of key downstream signaling cascades via transmembrane EP receptors located on the cell surface. Elevated levels of COX-2 and concomitant overproduction of PGE2 are often found in human cancers leading to the use of non-steroidal anti-inflammatory drugs (NSAIDs) as chemo preventive agents. Their long-term use, however, may be associated with gastrointestinal toxicity and increased risk of adverse effects. Targeting mPGES-1 is considered a valid alternative to the use of NSAIDs because it is an inducible enzyme able to affect only the prostanoids elicited by inflammatory stimuli without affecting those lipid mediators constitutively expressed. In the frame of my Ph.D. project, following a fragment-based approach and a structure-based drug design, a very promising mPGES-1 inhibitor was disclosed as well as a dual inhibitor of mPGES-1 and 5-lipoxygenase (5-LO). In the first case, a (4-phenyl-thiophen-2-yl)-acetic acid-based compound, SZK9, showed a high selectivity and a potent inhibitory activity against mPGES-1 (IC50 = 5.9 ± 1.0 μM). Since this molecule is endowed with a strong cytotoxic effect (IC50 = 10.1 ± 1.2 μM) comparable to the known inhibitor CAY10526 it can represent an attractive candidate for the development of new therapeutics in cancer pathology. In the second case, following a structure-based approach a 2,4-thiazolidinedione based molecule, TZ8, was identified as a potent inhibitor of both mPGES-1 and 5-LO, two key enzymes involved in inflammatory related disorders. Owing to its dual-target inhibitor profile TZ3 can be considered an interesting hit for the development of novel therapeutic interventions. [edited by Author]XXXIII cicl
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
A multidisciplinary functional proteomics-aided strategy as a tool for the profiling of a novel cytotoxic thiadiazolopyrimidone
Full text link: In recent years, thiadiazolopyrimidine derivatives have been acknowledged for their striking poly-pharmacological framework, thus representing an interesting scaffold for the development of new therapeutic candidates. This paper examines the synthesis and the interactome characterization of a novel bioactive thiadiazolopyrimidone (compound 1), endowed with cytotoxic activity on HeLa cancer cells. In detail, starting from a small set of synthesized thiadiazolopyrimidones, a multi-disciplinary strategy has been carried out on the most bioactive one to disclose its potential biological targets by functional proteomics, using a label-free mass spectrometry based platform coupling Drug Affinity Responsive Target Stability and targeted Limited Proteolysis-Multiple Reaction Monitoring. The identification of Annexin A6 (ANXA6) as compound 1 most reliable cellular partner paved the way to deepen the protein-ligand interaction through bio-orthogonal approaches and to prove compound 1 action on migration and invasion processes governed by ANXA6 modulation. The identification of compund 1 as the first ANXA6 protein modulator represents a relevant tool to further explore the biological role of ANXA6 in cancer, as well as to develop novel anticancer candidates
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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