1,721,238 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
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
The role of CHAP in muscle development, heart disease and actin signaling
Full text linkIn this thesis we investigated a novel Z-disc protein, cytoskeletal heart-enriched actin-associated protein (CHAP). Two isoforms of CHAP exist, encoded by one gene. The longer isoform CHAPa is predominately expressed in adult tissues, whereas CHAPb is expressed during cardiac and skeletal development. First, we investigated CHAP expression in adult mouse tissues in more detail and show that both CHAP isoforms are highest expressed in slow skeletal muscle fibers and vascular smooth muscle cells. In addition, we sequenced and investigated the expression of the chick CHAP isoform and show that CHAP expression in chick is similar to the expression observed in mouse embryo__s. To investigate the role of CHAP in vivo, we generated CHAP knockout embryonic stem cells, which can be used to generate CHAP knockout mice and we investigated the effect of morpolino mediated knockdown of CHAP in chick embryo__s. In addition, we generated heart specific CHAP transgenic (Tg) mice. Whereas in CHAPa Tg mice no phenotype was observed, CHAPb Tg mice developed cardiomyopathy with diastolic dysfunction. In addition, in the hearts of CHAPb Tg mice stress fibers were observed and the actin signaling pathway was activated. To study the effects of CHAP overexpression in vitro, we generated CHAP adenoviruses. We showed that although CHAPb also induced stress fibers in vitro, the actin signaling pathway was not activated, suggesting that this was not a direct effect in Tg mice. In addition, we showed that CHAPa is important for Z-disc integrity in vitro. Finally, we also showed that CHAP is expressed in the small intestine and kidney, and this expression is correlated with F-actin expression. These data show that CHAP is important for muscle development, Z-disc integrity and stability and actin signaling.Netherlands Heart FoundationUBL - phd migration 201
From teeth, skin, blood to heart : induced pluripotent stem cells as an in vitro model for cardiac disease
Full text linkSince the first reports of human induced pluripotent stem cells (hiPSC), the field of pluripotent stem cell (PSC) research has grown in leap and bounds, particularly in the area of (cardiac) disease modeling. This is in part because it is fairly easy to produce cardiomyocytes from hPSC and also there are now more assays available which can determine phenotypic behavior. This thesis describes and discusses improvements to reprogramming technology as well as its use in cardiac development and disease modelingPrinting of this thesis was supported by the Dutch Heart Foundation and BD biosciencesUBL - phd migration 201
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
Human embryonic stem cells : advancing biology and cardiogenesis towards functional applications l
Full text linkHuman embryonic stem cells (hESC) hold great potential as a model for human development, disease pathology, drug discovery and safety pharmacology. All these applications will depend on comprehensive knowledge of their biology and control of their signaling mechanisms and fate choices. To begin to address this, we developed a standardized feeder-free hESC culture protocol. This system is optimized and tested for 12 independently derived stem cell lines, and optimal for clonal growth and efficient gene transfer without loss of pluripotency (Chapter 2,3). Using these protocols we created stem cells ubiquitously expressing EGFP, showed efficient SOX2 knockdown and created a fluorescent reporter stem cell line for the stem cell regulator OCT4. Next we used mass spectroscopy to investigate the plasma membrane of hESC (Chapter 4). We were able to show that these cells express a uniform epithelial plasma membrane profile and that VIMENTIN, normally associated with mesenchymal cells is also expressed. This expression turned out to be related to stress and associated with hardness of the tissue culture plastic substrate rather than differentiation. We continued to investigate the plasma membrane of hESC and decided to focus on integrins, the cell surface receptors that bind extracellular matrix proteins. Functional analyses of their function showed human embryonic stem cells have the capacity to bind to a wide range of extracellular matrix proteins via specific integrin receptors. We were able to show that recombinant vitronectin robustly supports the maintenance of hESC in an undifferentiated state in completely defined culture medium. Having validated a completely defined culture protocol we began to investigate differentiation mechanisms under defined conditions (Chapter 5). We used Stable Isotope Labeling in Cell Culture (SILAC) and quantitative phopspho-proteomics to investigate how human embryonic stem cells exit the pluripotent state. BMP4 was used to trigger differentiation and protein samples were analyzed at 30 min, 60 min and 240 min. We showed that approximately 50% of the 3067 identified phosphosites were regulated within 1 hr of differentiation induction, revealing a complex interplay of phosphorylation networks spanning different signaling pathways. Among the phosphorylated proteins was the pluripotency-associated protein SOX2, which was SUMOylated as a result of phosphorylation. Using the data to predict kinase-substrate relationships we reconstructed the hESC kinome, with CDK1/2 emerging as a key kinase in controlling self-renewal and lineage specification. Next we used gene targeting to create a fluorescent cardiac reporter cell line. EGFP was targeted into one allele of the NKX2-5 gene. EGFP fluorescence driven by the endogenous Nkx2-5 promoter faithfully reported cardiovascular lineage commitment of differentiating hESC under defined culture conditions. Using fluorescence activated cell sorting we showed that the early NKX2-5 positive cell population contained multipotent progenitor cells capable of directed differentiation to cardiomyocytes, endothelial and vascular smooth muscle cells (Chapter 7). Finally, we used the cardiomcyocytes from hESC to develop a system for cardiac safety pharmacology (Chapter 8). Recent withdrawals of prescription drugs from clinical use because of unexpected side effects on the heart have highlighted the need for more reliable cardiac safety pharmacology assays. In particular, blocking of the human Ether-a-go go Related Gene ion channel is associated with life-threatening arrhythmias, such as Torsade de Pointes. We demonstrated that, as predicted, patient serum levels of drugs and known responses on QT interval overlapped with field potential duration values derived from hESC-CM,. On this basis, we propose field potential duration prolongation as a directly applicable safety criterion for pre-clinical evaluation of new drugs in development. In conclusion, the availability of human cardiomyocytes from stem cell sources is now expected to accelerate cardiac drug discovery and safety pharmacology by offering more clinically relevant human culture models than presently available (Chapter 9,10).The work presented in this thesis was carried out at the Hubrecht Institute (Utrecht) and the department of Anatomy & Embryology Leiden University Medical Center and was supported by a grant from the Dutch Program for Tissue Engineering. Financial support by the Netherlands Heart Foundation and the J.E Jurriaanse stichting for the publication of this thesis is gratefully acknowledged. Additional financial support was granted by Becton Dickinson, Boehringer Ingelheim BV and Multichannel Systems.UBL - phd migration 201
Modeling neurodegenerative diseases with human pluripotent stem cells
Full text linkThe discovery of human pluripotent stem cells has enabled the development of assays to model human disease in vitro. The research described in this thesis has focused on modeling Amyotrophic Lateral Sclerosis and Lesch Nyhan Syndrome using pluripotent stem cells. Chapter 1 contains the aim and outline of this thesis, Chapter 2 is introduction to the field and provides an overview of recent advances in stem cell modeling of Amyotrophic Lateral Sclerosis (ALS). Chapter 3 contains an introduction to the field of X-chromosome inactivation. In Chapter 4 we identify the Prostaglandin D2 DP1 receptor (DP1) as a therapeutic target for ALS and more generally validate that insights found in stem cell models of disease can be validated in vivo. In Chapter 5, we address whether non-steroidal anti-inflammatory drugs (NSAIDs) affect survival of motor neurons in ALS. In Chapter 6, we develop a stem cell assay to model Lesch Nyhan Syndrome (LNS). Finally, Chapter 7 is the general discussion of the work and contains a short perspective of the future.Boehringer Ingelheim Fellowship, Project ALS, NYSCF, NIHUBL - phd migration 201
- …
