1,721,041 research outputs found

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    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

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    “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

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    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

    Integrative Genomics Reveals a Role for GNA13 in Lymphomagenesis

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    Lymphomas comprise a diverse group of malignancies derived from immune cells. High throughput sequencing has recently emerged as a powerful and versatile method for analysis of the cancer genome and transcriptome. As these data continue to emerge, the crucial work lies in sorting through the wealth of information to hone in on the critical aspects that will give us a better understanding of biology and new insight for how to treat disease. Finding the important signals within these large data sets is one of the major challenges of next generation sequencing.In this dissertation, I have developed several complementary strategies to describe the genetic underpinnings of lymphomas. I begin with developing a better method for RNA sequencing that enables strand-specific total RNA sequencing and alternative splicing profiling in the same analysis. I then combine this RNA sequencing technique with whole exome sequencing to better understand the global landscape of aberrations in these diseases. Finally, I use traditional cell and molecular biology techniques to define the consequences of major genetic alterations in lymphoma.Through this analysis, I find recurrent silencing mutations in the G alpha binding protein GNA13 and associated focal adhesion proteins. I aim to describe how loss-of-function mutations in GNA13 can be oncogenic in the context of germinal center B cell biology. Using in vitro techniques including liquid chromatography-mass spectrometry and knockdown and overexpression of genes in B cell lymphoma cell lines, I determine protein binding partners and downstream effectors of GNA13. I also develop a transgenic mouse model to study the role of GNA13 in the germinal center in vivo to determine effects of GNA13 deletion on germinal center structure and cell migration.Thus, I have developed complementary approaches that span the spectrum from discovery to context-dependent gene models that afford a better understanding of the biological function of aberrant events and ultimately result in a better understanding of disease.</p

    Determining the Role of DDX3X in Normal and Malignant Germinal Center B Cells

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    Burkitt lymphoma (BL) is an aggressive germinal center (GC) B cell derived lymphoma. BL accounts for 40% of pediatric lymphoma cases in the United States and over half of all pediatric malignancies in Sub Saharan Africa. BL is characterized by the t(8;14) chromosomal translocation that results in MYC overexpression. Translocation of MYC alone is insufficient to induce lymphomagenesis; additional genetic mutations are required. A better functional characterization of the genetic drivers of BL will lend insight into pathways that drive Burkitt lymphomagenesis, providing an opportunity to identify novel drug targets and develop improved therapies. In order to identify novel genetic drivers of BL our lab previously sequenced 101 BL tumors with paired normal samples. We found that DDX3X is recurrently mutated in 46% of BL tumors, making it the third most commonly mutated gene in BL. We observed that DDX3X mutations are either truncating mutations (22%) or missense mutations (88%) that cluster around the two highly conserved functional domains of the protein. Based on the non-focal distribution of missense mutations throughout the DDX3X coding sequence and the high presence of truncation mutations in BL tumors, we hypothesize that in GC B cells DDX3X acts as a tumor suppressor gene whose normal function is destroyed by BL associated mutations, facilitating lymphomagenesis. While DDX3X is frequently mutated in many types of cancer, its role in malignancy is poorly understood. In this study we focused on elucidation of the role of DDX3X in the specific context of GC B cells from which BLs arise. To test the hypothesis that DDX3X normally functions as a tumor suppressor we modeled DDX3X deficiency in normal and malignant GC B cells using parallel in vitro and in vivo approaches. First, we created transgenic Ddx3x deficiency mouse models with and without MYC overexpression. This approach allowed us to study DDX3X in a system that models the complexities of the immune system on a genetically defined background. Second, we used genome editing to precisely delete DDX3X expression in BL cell lines. BL is a genetically complex disease and the the use of BL cell lines provides allowed us to study the role of DDX3X on a genetic background typical of BL tumors. We then characterized both DDX3X loss of function models with respect to cellular processes related to tumor development. Third, we performed cross-linking immunoprecipitation with sequencing (CLIP-Seq) to identify the RNA targets of DDX3X in the germinal center. Our study lead to unexpected results regarding the contribution of DDX3X to Burkitt lymphomagenesis, and highlighted an important role for DDX3X in B cell development. We found that Ddx3x deficiency in a mouse model of BL increased the time to tumor development by reducing the global B cell population available for malignant transformation. In tandem we found that Ddx3x deficiency at the GC B cell stage significantly reduced the GC B cell population in multiple lymphoid tissues, regardless of MYC status. Interestingly, we found that Ddx3x deficiency in pre-B cells expanded the pre-B cell population but decreased the population of later B cell stages. We then confirmed that the reduction of GC B cells in response to Ddx3x deficiency was not due to defects in GC B cell migration, germinal center architecture, cell cycle progression, or apoptosis. These combined data suggest an essential function for DDX3X in B cell development, particularly at the pre-B cell and GC B cell stages. Similar to in the mice, in cell culture we also found that DDX3X loss did not significantly alter apoptosis or cell cycle progression. We found some evidence that DDX3X may play a role in DNA damage repair but these results were not consistent across conditions. Lastly, we identified DDX3X targeted RNA binding partners using CLIP-Seq. Our data corroborates previously published CLIP-Seq experiments showing that DDX3X binds numerous RNAs involved in translation and RNA processing. Additionally, we identified for the first time that DDX3X binds RNAs falling in the BRCA1 and ATM gene sets. Further experimentation is needed to determine the role DDX3X plays in these pathways with relationship to Burkitt lymphomagenesis.</p

    Dispelling the Myths Behind First-author Citation Counts

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    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

    Author Index

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    koamabayili/VECTRON-author-checklist: VECTRON author checklist

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    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

    Overlapping nuclear import and export paths unveiled by two-colour MINFLUX

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    Abstract The nuclear pore complex (NPC) mediates nucleocytoplasmic exchange, catalysing a massive flux of protein and nucleic acid material in both directions 1 . Distinct trafficking pathways for import and export would be an elegant solution to avoid unproductive collisions and opposing movements. However, the three-dimensional (3D) nanoscale spatiotemporal dynamics of macromolecules traversing the NPC remains challenging to visualize on the timescale of millisecond-scale transport events. Here we used 3D MINFLUX 2 to identify the nuclear pore scaffold and then to simultaneously monitor both nuclear import and nuclear export, thereby establishing that both transport processes occur in overlapping regions of the central pore. Whereas translocation-arrested import complexes bound at the pore periphery, tracks of translocating complexes within the central pore region revealed a preference for an approximately 40- to 50-nm diameter annulus with minimal circumferential movement, indicating activity-dependent confinement within the permeability barrier. Movement within the pore was approximately 1,000-fold slower than in solution and was interspersed with pauses, indicating a highly restricted environment with structural constraints and/or transient binding events during transport. These results demonstrate that high spatiotemporal precision with reduced photobleaching is a major advantage of MINFLUX tracking, and that the NPC permeability barrier is divided into annular rings with distinct functional properties
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