1,721,039 research outputs found
Going Beyond Counting First Authors in Author Co-citation Analysis
The 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
“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
We 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
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Using Drosophila melanogaster to Study Tumor-Host Interactions
At its simplest, cancer can be defined as a disease of uncontrolled cell growth and proliferation. The genetic changes and consequences of these changes are now well-defined, owing to modern advances in molecular biology. These changes within a tumor cell extend beyond just the tumor itself. Tumor cells release a plethora of signals that alter the behavior of their cellular neighbors as well as the physiology of their host. Unlike the better-understood genetic changes that drive malignant transformation, the mechanisms that govern the myriad of ways tumors influence the behavior and physiology of distant host tissues remains opaque. We have developed a novel Drosophila adult ovarian tumor model that overcomes the drawbacks of existing tumor models and creates a unique opportunity to investigate the molecular mechanisms underlying tumor-host interactions. We analyzed the transcriptome of ovarian tumors and found to our surprise that ovarian tumors upregulate several clotting factors, leading us to hypothesize that tumors may interfere with host coagulation, reminiscent of a human paraneoplastic syndrome called disseminated intravascular coagulation. We found that the overproduction of Fondue, one of the clotting factors identified in our transcriptome, drives systemic coagulopathy in tumor-bearing flies, and knockdown of Fondue rescued multiple clotting defects. Importantly, Fondue knockdown significantly improved the survival of tumor-bearing flies compared to controls, indicating that Fondue-driven coagulopathy contributes to host mortality. We took advantage of the ovarian tumor model to perform an unbiased, forward genetic screen to search for novel mediators regulating tumor-host interactions. This screen made use of a library of deletions available to fly biologists, and we identified two potential candidate genes that may play a role in tumor-host interactions – NKCC and tartan. Although we were unable to identify a specific mechanism, our current results suggest that NKCC may regulate paraneoplastic dysregulation of ion homeostasis, while the mechanism through which tartan acts requires further investigation. Additional work using the ovarian tumor model suggested the existence of a previously unidentified paraneoplastic syndrome that manifests as defects in heart physiology. Thus, our work builds upon previous work on tumor-host interactions in Drosophila and demonstrates the power of the ovarian model to study paraneoplastic syndromes
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Roles of Cellular and Humoral Immunity in Drosophila Tumor-Host Interactions
Cancer has plagued humanity for thousands of years and continues to be a leading cause of death globally. While tumor growth has been well-characterized, the interactions between a tumor and its host remain understudied. Long-distance tumor-host interactions are known as paraneoplastic syndromes – a class of diseases that affect various organs and present as diverse clinical symptoms. These interactions can be potent drivers for patient mortality, and a deeper understanding of them could have therapeutic benefits. One paraneoplastic syndrome of particular interest is that of the tumor and the immune system. This interaction is the foundation of powerful cancer immunotherapies, but aspects of the tumor-immune cell dynamic remain a mystery. In recent years, Drosophila melanogaster has emerged as a model system to study these and other tumor-host interactions. By leveraging the fly’s powerful genetics and conserved biology, researchers can probe molecular mechanisms that would be difficult to study in mammals. Here, we used the powerful fly system to better understand cellular and humoral immunity and systemic responses to cancer. Tumor-immune interactions are important drivers of tumor growth and host lethality. Using an adult autochtonous ovarian carcinoma (OC) tumor model, we demonstrate that these tumors recruit macrophages similar to mammalian tumors and that the presence of tumor-associated macrophages slows tumor progression and increases host lifespan. Mammalian tumors acquire ways to evade the immune system; however, it is unknown whether fly tumors can do the same. Interestingly, OC tumors secrete a conserved GPI-linked protease inhibitor called Thioester-containing Protein 3 (Tep3), which we find restricts immune cell recognition of the tumor and thus accelerates tumor progression and host death. We show that Tep3 inhibits the matrix metalloprotease MMP1’s proteolytic activity to prevent tumor basement membrane breakdown, a known recruitment signal for macrophages, and thus limit immune restriction of the tumor. Excitingly, Tep3 is also produced in wounds in conjunction with MMP1 where it similarly blocks macrophage recruitment to the wound by modulating MMP1 activity. Tep3 seems to act as a negative regulator of the inflammatory response to resolve inflammation and prevent tissue damage. Hence, the tumor is able to exploit this normal physiological anti-inflammatory mechanism to evade the immune system. Along with cellular responses, fly tumors also trigger humoral signaling that plays a vital role in tumor-host interactions. While previous work has focused on understanding effects exerted by the tumor on the host, I am interested in how host tissues systemically respond to a tumor. I used a transcriptomic approach to address this question. RNA sequencing of host fat body (the major secretory organ; analogous to human fat and liver) in the presence of a tumor uncovered upregulated factors predicted to be secreted from host fat body. Comparison of the response to tumor versus that to a novel serial clean wounding revealed that the tumor generates a distinct response in host fat, more akin to other chronic stresses like starvation. Using an allograft lifespan assay as a primary screen, I have identified candidates that when knocked down in the fat body affect cancer-induced host mortality. I have also built fly lines compatible with the lab’s GAL4-independent tumor model that can now be used for further testing. These transcriptomes will be a valuable resource on systemic host response to tumors. Thus, my work has advanced our understanding of Drosophila tumor-immune cell interactions and laid a foundation for future studies on systemic host response
Dispelling the Myths Behind First-author Citation Counts
We 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
We 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
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Mechanisms of basolateral polarity determination by the Scrib module
Cell polarity is a fundamental process in biology whereby a single cell can partition its plasma membrane into two distinct and non-overlapping domains. All cells are polarized, and cell polarity is essential for the development and homeostasis of many tissues and organs. Epithelial cells exhibit a form of polarity called apicobasal polarity that is regulated by the activity of two conserved protein groups: the Par complex, which specifies the apical domain, and the Scrib module, which, in many contexts, is required to specify the basolateral domain. Mutual antagonism between the Par complex and the Scrib module positions the apical-basolateral boundary and primarily involves the apical kinase aPKC and its substrate and inhibitor, the basolateral protein, Lgl. While the mechanisms underlying apical polarity determination by the Par complex are well-studied, the molecular basis for basolateral polarity establishment by the Scrib module proteins, Scrib, Dlg and Lgl are unclear. In this dissertation I investigate the individual functions of Scrib, Dlg and Lgl using genetic manipulations and biochemistry in Drosophila and describe distinct and cooperative activities that give rise to basolateral polarity.I identified regulatory relationships between Scrib, Dlg and Lgl that govern their localization to the cell cortex and demonstrated that these three proteins possess unique, but cooperative activities that are required but not sufficient to establish the basolateral domain. I found a specific requirement for Dlg to localize Scrib and investigated potential mechanisms, ruling out previously proposed binding interactions and posttranslational modification. I described a requirement for Scrib and Dlg to control Lgl localization by negatively regulating its phosphorylation by aPKC. We proposed a model where Scrib and Dlg ‘protect’ Lgl at the basolateral membrane, activating Lgl’s aPKC-inhibiting potential and limiting apical domain spread.To define the molecular mechanisms of these observations, I investigated Dlg protein function in detail. I identified a putative PP1-binding motif in the Dlg HOOK domain that was essential for Dlg function, however I did not find evidence for Dlg-PP1 physical interaction and although PP1 regulates Lgl phosphorylation, the ability of Dlg and Scrib to regulate Lgl is largely separate from PP1. However, study of Dlg PP1-binding mutants revealed the requirement of the Dlg HOOK domain in localizing Scrib to the cortex. Using this information and a panel of structure-function constructs, I defined a minimal fragment consisting of only the SH3 and HOOK domains that was necessary and sufficient for function, including Scrib recruitment.To investigate other mechanisms of Dlg function, I collaborated with Katherine Sharp, a postdoc in the lab, to interrogate Dlg binding partners using APEX2-based proximity proteomics. Our results revealed a large number of nuclear proteins in proximity to Dlg in vivo. We found that a population of endogenous Dlg resides in the nucleus near to the NURF chromatin remodeling complex. Overgrowth of dlg mutant tumors was dependent on NURF complex activity and may result from NURF-dependent activation of Yki target genes. We identified a putative NLS sequence in the Dlg HOOK domain and demonstrated that this motif is essential for Dlg function, but its mutation does not prevent Dlg nuclear entry, suggesting the existence of an alternate NLS.Together, the work presented in this dissertation constitute an important advance in the understanding of the molecular functions of the Scrib module proteins, Scrib, Dlg and Lgl and provide a plausible model underlying basolateral polarity via our proposed Lgl protection mechanism. These studies set the stage for future investigation of the overarching mechanisms that polarize animal cells and will enable fuller understanding of many fundamental cell polarity-dependent biological processes
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