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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
Self-oligomerization of the hydrophobic regions within amyloid beta and prion protein
No full textProteinopathies of the central nervous system (CNS) encompass a broad range of disorders (Alzheimer, Parkinson, Huntington and prion diseases) which invariably lead to human neurodegeneration. Such diseases bear a heavy financial burden on healthcare and elevate socio-economic costs, and will continue to do so as the general population ages. In our current predicament, there is a lack in etiological treatments for such diseases, rendering them incurable and unpreventable. Consensus in the field of translational research has attributed disease pathology to the misfolding and aggregation of certain proteins. The work in this thesis examines two highly aggregating proteins found in Alzheimer and Prion diseases, beta amyloid (Aβ) and prion protein (PrP) respectively, in efforts to assist in the development of rationally designed therapies. Intriguingly, both proteins possess highly hydrophobic stretches rich in small amino acids such as glycine (G) and alanine (A), which can organize to form motifs that determine their synthesis, trafficking, folding, processing and degradation in cells. The guiding hypothesis is that such regions in these proteins may provide for a valid molecular target for therapeutic intervention.Recently, a human mutation within the highly conserved hydrophobic region of PrP (glycine 127 exchanged to valine) was characterized to confer complete neuroprotection from infectious prions. Similarly, other familial mutations and polymorphisms which exist in this very region have been shown to elicit or potentiate various prion disease phenotypes. Interestingly, of the mutations cataloged to date, the pathogenic and protective mutations seem to exist separately at two distinct motifs within the hydrophobic region of PrP: namely its N-terminal AGAAAAGA palindrome and C-terminal GxxxG-like motifs. In efforts to understand how such mutations alter the behavior of PrP, I examined their effects on oligomerization of the hydrophobic region within the lipid bilayer environment. As the entirety of the region is heavily implicated in the biogenesis and misfolding of PrP, the findings described here may help provide mechanistic insight on how one could develop a therapeutic agent that could target these motifs to exert effects much like the G127V mutation. Like PrP, Aβ also possesses a hydrophobic region notorious for aggregation and involvement in neurodegeneration. This region also contains a triple repeat GxxxG motif, which has been dually implicated in the biogenesis and toxicity of Aβ peptides. As such, I have examined certain compounds that can modulate generation of these peptides (γ-secretase modulators), to examine if they can interact with GxxxG motifs to elicit their therapeutic effects. In addition to this, I have also developed a facile method for the production of the most toxic and highly aggregating Aβ species, Aβ 1 - 42. As synthetically derived Aβ counterparts have lower toxicity, slower aggregation kinetics, and are commercially inflated in price, this production method for recombinant Aβ will help expedite our efforts in the realization of a molecular candidate that can neutralize the toxicity of this peptide; an integral strategy for the treatment of Alzheimer disease.Les protéinopathies du système nerveux central (SNC) englobent une large gamme de troubles (maladie d'Alzheimer, Parkinson, Huntington et maladie à prions) qui conduisent invariablement à une neurodégénérescence humaine. De telles maladies ont un lourd poids financier pour les soins de santé et augmentent les coûts socioéconomiques, et continueront à faire à mesure que la population générale vieillira. Dans notre situation actuelle, il y a un manque de traitements étiologiques pour de telles maladies, les rendant incurables et inévitables. Le consensus établi par le domaine de la recherche translationnelle attribue la pathologie au repli et à l'agrégation de certaines protéines. Ce travail de thèse examine deux protéines hautement agrégées trouvées dans les maladies d'Alzheimer et à prions, la protéine β-amyloïde (Aβ) et la protéine prion (PrP), dans le but d'aider au développement de thérapies rationnellement conçues. De façon intéressante, les deux protéines possèdent des domaines hautement hydrophobes riches en petits acides aminés tels que la glycine (G) et l'alanine (A), qui peuvent s'organiser pour former des motifs qui déterminent leur synthèse, leur trafic, leur repliement, leur transport et leur dégradation dans les cellules. L'hypothèse directrice est que de ces domaines pourraient fournir une cible moléculaire valide sur le plan thérapeutique.Récemment, une mutation humaine dans la région hydrophobe hautement conservée de PrP (glycine 127 remplacée par une valine) a été caractérisée. Elle entraine une neuroprotection complète contre les infections par les prions. De même, d'autres mutations familiales et des polymorphismes qui existent dans cette même région ont été montrés pour entrainer ou potentialiser divers phénotypes de la maladie à prions. Parmi les mutations mises en évidence à ce jour, il est intéressant d'bbserver que les mutations pathogènes et protectrices semblent exister séparément dans deux motifs distincts dans la région hydrophobe de PrP, à savoir : le palindrome N-terminal AGAAAAGA et les motifs C-terminaux GxxxG. Dans le but de comprendre comment de telles mutations altèrent le comportement de la PrP, j'ai examiné leurs effets sur l'oligomérisation de la région hydrophobe dans l'environnement de la bicouche lipidique. Étant donné que la totalité de la région est fortement impliquée dans la biogenèse et le repliement de la PrP, les découvertes décrites ici peuvent aider à fournir un aperçu mécanistique de la façon dont on pourrait développer un agent thérapeutique qui pourrait cibler ces motifs afin d'exercer des effets similaires à ceux de la mutation G127V.Comme PrP, Aβ possède également une région hydrophobe connue pour avoir un rôle dans l'agrégation et être impliquée dans la neurodégénérescence. Cette région contient également un motif GxxxG à répétition triple, impliqué dans la biogenèse et la toxicité des peptides Aß. Ainsi, j'ai examiné certains composés qui peuvent moduler la génération de ces peptides (modulateurs des γ-sécrétases), afin de determiner s'ils sont capables d'interagir avec des motifs GxxxG et induire leurs effets thérapeutiques. De plus, j'ai développé une méthode simple de production des espèces Aβ les plus toxiques et possédant une capacité élevée à s'agréger, Aβ 1 - 42. Comme les dérivés homologues de synthèse de Aβ ont une toxicité plus faible, une cinétique d'agrégation plus lente et des prix très élevés sur le marché, cette méthode de production pour l'Aß recombinant aiderait à accélérer nos efforts dans l'élaboration d'un candidat moléculaire qui pourrait neutraliser la toxicité de ce peptide ; une stratégie complète pour le traitement de la maladie d'Alzheimer
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
Genetische und chemische hydrophobe Modifikation von Transkriptionsfaktor-Kondensaten bei menschlichen Erkrankungen
No full textThe work in this thesis examines how hydrophobic modifications within intrinsically
disordered regions (IDRs) of transcription factors (TFs), caused by genetic mutations and
drug-induced changes, disrupt TF condensation and gene expression programs in various
human disease states. I establish as a general paradigm that disease-associated poly-alanine
repeat expansions promote the formation of homotypic TF condensates with gel-like material
properties, at the expense of heterotypic interactions with other components of the
transcriptional apparatus. This effect was elicited by hydrophobic repeat expansions found in
the following developmental disorders: synpolydactyly (SPD), cleidocranial dysplasia
(CCD), and hand-foot-genital-syndrome (HFGS). Utilizing insights from this paradigm, I
hypothesized that the condensation capacity of TFs may be controlled with chemical
modifiers of TF-IDRs, in efforts to treat diseases reliant on aberrant transcriptional programs,
such as cancer. To this end, this thesis provides evidence that the condensation of an
oncogenic transcription factor, the androgen receptor (AR), can be targeted with small
molecules that selectively partition into condensates formed by the disordered activation
domain of the AR. Increasing the hydrophobicity of the small molecule resulted in higher
potency in the arrest of proliferation and AR-driven gene expression programs in a human
model of prostate cancer (PCa). Together, these results suggest that hydrophobic
modification of transcription factors and small molecules that partition into condensates can
be leveraged for therapeutic intent.In dieser Dissertation wurde untersucht, wie hydrophobe Modifikationen innerhalb
von intrinsisch ungeordneten Regionen (IDRs) von Transkriptionsfaktoren (TFs), verursacht durch genetische Mutationen und arzneimittelinduzierte Veränderungen, die TF-
Kondensation und Genexpressionsprogramme in verschiedenen menschlichen Krankheitsstadien stören. Dadurch konnte etabliert werden, dass krankheitsassoziierte Poly-
Alanin-Expansionen die Bildung von homotypischen TF-Kondensaten mit gelartigen Materialeigenschaften fördern, auf Kosten heterotypischer Wechselwirkungen mit anderen
Komponenten des Transkriptionsapparates. Dieser Effekt wurde in folgenden
Entwicklungsstörungen charakterisiert: Synpolydaktylie (SPD), cleidocraniale Dysplasie
(CCD) und Hand-Fuß-Genital-Syndrom (HFGS). Basierend auf diesen Erkenntnissen folgte
die Hypothese, dass die Kondensationskapazität von TFs mit chemischen Modifikationen von
TF-IDRs kontrolliert werden kann, um Krankheiten wie z.B. Krebs zu behandeln, die auf
abweichende Transkriptionsprogramme angewiesen sind. In diesem Zusammenhang konnte
ich in meiner Dissertation belegen, dass die Kondensation eines onkogenen
Transkriptionsfaktors, des Androgenrezeptors (AR), mit kleinen Molekülen moduliert werden
kann, die sich selektiv in Kondensate integrieren, die von der ungeordneten
Aktivierungsdomäne des AR gebildet werden. Eine Erhöhung der Hydrophobie dieses
Moleküls führte zu einer stärkeren Hemmung von Proliferations- und AR-gesteuerten
Genexpressionsprogrammen, welche in einem menschlichen Prostatakrebsmodell (PCa)
nachgewiesen wurde. Zusammengenommen legen diese Ergebnisse nahe, dass die
hydrophobe Modifikation von Transkriptionsfaktoren und kleine Moleküle, die sich in
Kondensate integrieren, für therapeutische Zwecke genutzt werden kann
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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