1,720,955 research outputs found
Recovery of Markers through Insonation: An alternative to monitoring gene expression in deep tissues
No full textWe developed a method to noninvasively measure transgene expression in the specific brain regions using a blood test.
To achieve this, we used engineered protein reporters that are released from the cells into the brain interstitium. We then used focused ultrasound (FUS) to transiently open the blood-brain barrier (BBBO) and release these reporters into the blood. We call this approach REcovery of Markers through InSonation, or REMIS.
We show that levels of markers secreted from neurons into the serum correlate with the levels of transgene expression in the brain. We measured up to 5.5-fold increase of marker levels in the blood after opening of 8% of the blood-brain barrier (BBB). We show the procedure is well tolerated and avoids significant tissue damage, consistent with other BBB opening studies. Finally, we show that the marker is released from the brain over prolonged periods of time. The levels of the released marker were comparable at 7.5 minutes and 2 hours after FUS-BBBO (p=0.31, paired t-test). At the same time, the serum half-life of the marker injected intravenously was 7.6 minutes. This suggests that the marker was released from the brain gradually, replenishing the marker in the serum over 2 hours, and indicating a broad time window available for marker collection.
Monitoring gene expression in deep tissues of living animals is critical for in vivo studies and translation of gene therapies. This technology allows for site-specific measurement of gene expression in the brain
Acoustically targeted measurement of transgene expression in the brain
No full textGene expression is a critical component of brain physiology and activity. Brain development, function, and plasticity relies on a regulated process of converting genetic information into functional products. However, monitoring gene expression in the living brain has been a significant challenge. The confined structure of the brain, protected by the cranium and shielded by the blood-brain barrier, has posed difficulty in non-invasive and sensitive measurement of gene expression with specificity. The aim of this thesis is to develop a new paradigm of technology capable of measuring gene expression in the brain non-invasively with cell-type, spatial, and temporal specificity. To achieve this, we combined focused ultrasound liquid biopsy and recovery of engineered protein markers that are designed to be expressed in neurons and exit into the brain’s interstitium. When ultrasound is applied to targeted brain regions, it temporarily opens the blood-brain barrier and releases the interstitial markers into the bloodstream. Once in blood, the markers can be readily detected from blood collection followed by compatible biochemical techniques. We call this Recovery of Markers through InSonation (REMIS). We demonstrated improved recovery of engineered Gaussia luciferase marker, under constitutive promoter, from the brain into the blood in every tested animal. Further, we implemented the markers to measure endogenous neuronal signaling activity by controlling the expression of the marker under a genetic circuit that responds to c-Fos when activated by enhanced neuronal activity. Lastly, we measured enhanced serum level of overexpressed human alpha-synuclein in the engineered Parkinson’s disease model mThy1-aSyn (Line61) mouse strain with REMIS. Overall, our work demonstrates the feasibility of combining engineered gene expression reporters and focused ultrasound liquid biopsy to noninvasively and specifically measure gene expression in the intact brain
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Get PDF“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
Get PDFWe 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
Get PDFWe 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
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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