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Generation of Human Microglia from Induced Pluripotent Stem Cells to Study Innate Immunity in Neurological Diseases.
Microglia play an important role in developmental and homeostatic brain function. They profoundly influence the development and progression of neurological disorders, including Alzheimer’s disease (AD). In AD, microglia respond to degenerating neurons, beta-amyloid (Aβ) and tau pathology, and CNS inflammation. AD-etiology involves complex interactions between age, genetic, and environmental risk factors. Recently, GWAS studies in large AD cohorts have identified numerous SNPs present in innate immune genes, many expressed in microglia. These SNPs confer an elevated risk in developing AD, and harboring of these SNPS is considered a risk factor. While the genes themselves are not risk factors, SNPs in these genes may impair the normal function of microglia, such as cytokine production and phagocytosis. Furthermore, many of these genes are involved in the detection or clearance of Aβ, and therefore these SNPs may collectively influence microglia function or influence dysfunction.Studying human microglia is challenging because of the rarity and difficulty in acquiring cells from human CNS tissue. A methodology for generating human microglia from a renewable source has long remained elusive despite success in generating the other cell-types of the CNS. This elusiveness existed due to the ontogeny of microglia and their unique transcriptome and functional differences versus other myeloid cells. The goal of my dissertation was to generate human induced pluripotent stem cell (iPSC)-derived microglia (iMGLs) to study their molecular and physiological function in neurological disease. To accomplish this goal, I developed a fully-defined protocol to generate large number of pure (>95%) iMGLs under 40 days. iMGLs are highly like primary human microglia as assessed via whole-transcriptome and functional analyses. iMGL studies, in vitro and in vivo, highly suggest that they can be used as surrogates for human p microglia. Using iMGLs, I showed how AD-GWAS related microglial genes were influenced by two hallmark AD proteins—Aβ and Tau. In addition, I showed that iMGLs populate mouse brains and develop microglial-like arborized morphology and respond to Aβ in an AD transgenic mice. Together, this protocol represents an important advance in our ability to study human microglia in the context of development, health, and disease, such as A
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
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
Author-wise bibliometric analysis based on entropy.
Author-wise bibliometric analysis based on entropy.</p
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