1,721,177 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
40 th "A. Corbella" International Summer School on Organic Synthesis - ISOS 2015
No full textHistone demethylases (HDMs) are epigenetic enzymes that remove a methyl group from histone tails, acting as erasers of the epigenetic code.1 Basing on their enzymatic mechanism, HDMs can be grouped into two classes: FAD-dependent HDMs (including monoaminoxidases) and Jumonji C domain containing HDMs that are Fe2+ and α-ketoglutarate-dependent hydrolases.2 The substrate residues of this latter include H3K4, H3K9, H3K27 and H3K36 at all methylation states. In particular, the focus of this study is JMJD3, that specifically demethylates 'Lys- 27' of histone H3.3 It has been reported that these lysine demethylases (JHDM) are associated with several diseases, such as bladder cancer, prostate carcinoma, breast cancer, Hodgkin lymphoma.4 With the aim of discovering new potential inhibitors of this HDM as attractive candidates for the development of anticancer drugs,4 we have designed and synthesized a small collection of 4-substituted-pyridine-2,6-dicarboxylic acids. These molecules contain as scaffold the dipicolinic acid, which has been selected from a large library of fragments through computational studies, suggesting a good interaction with the catalytic site of JMJD3. The experimental binding affinities of the synthesized molecules towards the target protein are currently under evaluation by Differential Scanning Fluorimetry assay (DSF) and further biological assays.
References
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
40 th "A. Corbella" International Summer School on Organic Synthesis - ISOS 2015
No full textHistone demethylases (HDMs) are epigenetic enzymes that remove a methyl group from histone tails, acting as erasers of the epigenetic code.1 Basing on their enzymatic mechanism, HDMs can be grouped into two classes: FAD-dependent HDMs (including monoaminoxidases) and Jumonji C domain containing HDMs that are Fe2+ and α-ketoglutarate-dependent hydrolases.2 The substrate residues of this latter include H3K4, H3K9, H3K27 and H3K36 at all methylation states. In particular, the focus of this study is JMJD3, that specifically demethylates 'Lys- 27' of histone H3.3 It has been reported that these lysine demethylases (JHDM) are associated with several diseases, such as bladder cancer, prostate carcinoma, breast cancer, Hodgkin lymphoma.4 With the aim of discovering new potential inhibitors of this HDM as attractive candidates for the development of anticancer drugs,4 we have designed and synthesized a small collection of 4-substituted-pyridine-2,6-dicarboxylic acids. These molecules contain as scaffold the dipicolinic acid, which has been selected from a large library of fragments through computational studies, suggesting a good interaction with the catalytic site of JMJD3. The experimental binding affinities of the synthesized molecules towards the target protein are currently under evaluation by Differential Scanning Fluorimetry assay (DSF) and further biological assays.
References
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
Identification of anti-resorptive and anti-cancer activities of epigenetic inhibitors
Full text linkMultiple myeloma is a plasma cell malignancy and develops in the bone marrow. The myeloma bone disease is present in the majority of the myeloma patients and is characterised by the excessive numbers and increased resorptive functions of osteoclasts. In order to identify novel targets controlling both osteoclastogenesis and myeloma cell growth, a library of epigenetic compounds was screened in an osteoclast differentiation assay and myeloma cell viability assay. Some compound classes, such as BET bromodomain inhibitors and HDAC inhibitors, showed inhibitory effects on both osteoclast differentiation and myeloma cell proliferation, suggesting that chromatin modifying reagents are possible therapeutic targets in multiple myeloma treatment. To rapidly screen for anti-osteoclast effects, an osteoclast RANKL gene card was successfully developed and applied to selected inhibitors in osteoclast assays. Moreover, the transcriptomic analysis was used to investigate the underlying mechanisms of selected epigenetic compounds in myeloma cells, and we found that cell cycle related pathways have been regulated by several inhibitors. Furthermore, an antibody panel for CyTOF (Mass cytometry) has been developed to characterise the bone marrow microenvironment of myeloma patients, and the CyTOF experiments demonstrated that GSK-J4 and rocilinostat activate the apoptosis marker caspase3 only in myeloma cells without affecting other cell populations. GSK-J4, an inhibitor for KDM5 and KDM6, was shown to upregulate the metallothioneins and induce the ATF4-mediated stress response in myeloma cells, whereas the KDM5B inhibitors causes cell cycle arrest rather than apoptosis.</p
Investigation into structural and functional relationships of short-chain dehydrogenases and reductases (SDRs) using a compound library
Full text linkThe short-chain dehydrogenases/reductases (SDR) protein family is one of the largest and most evolutionarily conserved protein superfamilies known to date. SDRs show a remarkable ability to accommodate hundreds of reactions/substrates by using the versatile nucleotide binding domain as their central scaffold. SDRs are implicated in many different disease pathways, and represent a ‘druggable’ enzyme class, which has generated extensive biotechnological and pharmaceutical interest. For 28 human SDR members, the three- dimensional structures have been determined. Despite this, almost 25 % of human SDR members still have unknown functions, and many members lack any chemical descriptors. To address the dearth of ligand knowledge, 28 SDRs were cloned, expressed and purified to further characterise members by the application of differential scanning fluorimetry (DSF). A family annotation through cofactor preference, substrate accommodation and subcellular localisation has shown a few distinctive traits within the SDR family. This in silico approach has led to the creation of a systematic flow chart, which provides a starting point to identify substrate classes for orphan SDRs. Cofactor and inhibitor screening of SDRs by DSF has shown Tm shifts that are in-line with previous experimental data. DSF screening showed the decryption of 6 cofactor preferences for orphan SDRs, five of which have been confirmed in crystal structures. In contrast, screening of substrates in DSF produce little thermal stability (15 % detection rate), rendering it difficult to distinguish specific substrates for orphan SDRs. However, over 70 % of SDRs screened in DSF with known enzyme activity produce thermal shifts with compounds that resemble their substrate structures. This can therefore infer substrate classes for orphan SDRs that compare well with those from computational predictions. DSF screening against a ligand library has led to the discovery of the first small molecule binders for Nmr-like family domain-conatining protein 1 (NMRAL1) and selective inhibitors for Hydroxyprostaglandin dehydrogenase (HPGD). The use of small molecule ligands identified from DSF has also contributed to the success of crystal formation in the case of Hydroxysteroid dehydrogenase-like protein 2 (HSDL2) and Dehydrogenase/reductase SDR family member 2 (DHRS2). Overall this study has provided a platform for ligand screening to further structurally characterise the SDR family
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
- …
