1,721,040 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
Contribution of transmembrane domain V amino acids to β1l-adrenoceptor activity and affinity
No full textIntroduction. There are two binding sites on the β1-adrenoceptor (AR), β1H and β1L corresponding to high and low affinity binding sites respectively, which can be activated to cause cardiostimulation. Some β-blockers that block β1AR and β2ARs can activate β1LARs at higher concentrations than those required to cause blockade. The β2AR does not form a corresponding low affinity binding site and therefore we postulated that heterologous amino acids are responsible for the formation of β1LAR. \ud
Aim. To investigate whether heterologous amino acids of transmembrane domain V (TMDV) of β1AR and β2ARs contribute to β1LAR. \ud
Methods. β1ARs, β2ARs and mutant β1ARs containing all (β1(β2TMDV)AR) or single amino acids of TMDV of the β2AR were prepared and stably expressed in Chinese Hamster Ovary cells. Concentration-effect curves for cyclicAMP accumulation were carried out for (-)-CGP12177 in the absence or presence of (-)-bupranolol. \ud
Results. The potencies (pEC50) of (-)-CGP12177 were β2AR (9.24 ± 0.14, n = 5), β1(V230I)AR (9.07 ± 0.07, n = 10), β1(β2TMDV)AR (8.86 ± 0.10, n = 15), β1(R222Q)AR (8.09 ± 0.29, n = 6), β1AR (8.00 ± 0.11, n = 11). The affinities (pKB) of (-)-bupranolol were β2AR (9.82 ± 0.52, n = 5), β1(V230I)AR (7.64 ± 0.12, n = 8), β1(β2TMV)AR (8.06 ± 0.17, n = 8), β1(R222Q)AR (7.33 ± 0.23, n = 5), β1AR (7.23 ± 0.23, n = 5). \ud
Discussion. The potency of (-)-CGP12177 was higher at β2AR than at β1AR consistent with activation through a low affinity site at the β1AR (β1LAR). The presence of V230 in β1AR accounted for the lower potency of (-)-CGP 12177. The affinity of (-)-bupranolol was lower at β1AR compared to β2AR. The presence of V230 in β1AR accounted in part for the lower affinity. In conclusion TMDV of the β1AR contributes in part to the low affinity binding site of β1AR. \u
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
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
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
Characterisation of PACAP-responsive receptor pharmacology and expression in cell models and the spinal cord
No full textPituitary adenylate cyclase-activating peptide (PACAP) is a neuropeptide that is widely expressed and involved in several biological processes, including pain. PACAP exists in two biologically active forms; PACAP-27 and PACAP-38. PACAP is closely related to vasoactive intestinal peptide (VIP) and peptide histidine methionine (PHM). These peptides activate three different class B G protein-coupled receptors; the PAC1, VPAC1 and VPAC2 receptors. To add further complexity, the PAC1 receptor may be alternatively spliced, generating variants that can differ in their agonist or signalling profiles. The PACAP peptide family show promise for the treatment of pain. To target these receptors therapeutically, we need to understand their underlying pharmacology and identify PACAP-responsive receptors at sites involved in pain. However, currently the pharmacological profiles are incomplete and receptor expression in tissue is typically limited to mRNA, which is not sufficient to link the physiological functions to a specific receptor. Therefore, the aim was to fully characterise human PACAP-responsive receptor pharmacology and translate these findings from cell model systems to human spinal cord tissue.
Chapter 3 investigated the activation of multiple signalling pathways by all endogenous agonists at all human PACAP-responsive receptor subtypes, including an N-terminal PAC1 receptor splice variant. These receptor profiles were further defined using receptor antagonists. To translate these findings into a relevant endogenous system, chapter 4 examined these responses at PACAP-responsive receptors in rat spinal cord cultures. Chapter 5 validated several antibodies targeting PACAP-responsive receptors, which were then utilised in chapter 6 to translate the functional signalling responses in spinal cord cultures to specific receptor subtypes expressed in the rat and human spinal cord. The blockade of PACAP-responsive receptors in the spinal cord could be beneficial in alleviating pain; therefore, chapter 7 used a proof-of-concept approach to explore the functionality of dual CGRP/PACAP receptor antagonists in cell models.
PACAP-responsive receptors were found to exhibit distinct pharmacological profiles but activated signalling in a similar manner. Of particular importance was the differential profile between the PAC1 receptor splice variants, which has significant implications for drug development and linking the physiological functions of an agonist to a specific receptor subtype. Additionally, PACAP-responsive receptor antagonists displayed agonist-dependent responses, an important consideration when screening novel antagonists targeting this family. Endogenous PACAP-responsive receptors in spinal cord cultures exhibited a PAC1 receptor-like pharmacological profile. PAC1 and VPAC2 receptor expression was identified in both rat and human spinal cord. These receptors exhibited differential localisation and therefore, may have diverse roles in pain. Furthermore, linking two peptide antagonists to form a dual CGRP/PACAP receptor antagonist was found to generate potent blockers of signalling for both receptors. This thesis provides new insight into the pharmacological profiles of PACAP-responsive receptors, including their splice variants, and identified their expression at a site important in pain to help facilitate future development of therapeutics targeting this receptor family
Understanding the regulation of CGRP-responsive receptors
No full textFull Text is available to authenticated members of The University of Auckland only.Migraine is a prevalent and debilitating neurological disorder that afflicts ~15% of the population. There is increased release of the neuropeptide, calcitonin gene-related peptide (CGRP) during a migraine attack which binds two G protein-coupled receptors (GPCRs): the CGRP and AMY₁ receptors. CGRP receptor regulation has been previously researched. However, there is very little information on the AMY₁ receptor regulation. The aim of this thesis is to compare the regulation mechanisms of these two CGRP-responsive receptors, primarily through investigating receptor internalisation. Internalisation of the receptors was investigated using fluorescently labelled CGRP. The CGRP receptor internalised robustly and was present in the cytosol. In comparison, the AMY₁ receptor remained at the cell surface. The location of the receptors were further investigated using immunofluorescence. The CGRP receptor colocalised with early endosome antigen 1 (EEA1), indicating its presence in early endosomes. There was little colocalisation seen for the AMY₁ receptor and EEA1. In addition, the interaction between a key internalisation protein, βarrestin, was investigated. Stimulation with CGRP saw translocation of the fluorescently labelled β-arrestin2 to the cell surface and then to the cytosol for the CGRP receptor. βarrestin2 remained diffuse in the cytosol for the AMY₁ receptor. Receptor interactions with βarrestin were further investigated using chemical cross-linking. β-arrestin was cross-linked to the CGRP receptor with an increase in β-arrestin binding upon stimulation. Internalisation was further explored using sucrose density centrifugation, where the CGRP receptor was isolated from early endosomes and β-arrestin was also found in the early endosome fraction. The findings in this thesis indicate two distinct regulation mechanisms for the CGRP and AMY₁ receptors. The CGRP receptor internalised into early endosomes through an interaction with β-arrestin whereas the AMY₁ receptor did not robustly internalise and did not appear to have an interaction with β-arrestin. This research is able to give insight into the cellular processes that may be occurring in migraine. Understanding the difference in regulation of these receptors is important as it will help provide more effective migraine drug development through knowledge of which receptors may be active in different cellular compartments
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