1,721,033 research outputs found
Singularities of the curve shrinking flow for space curves
No full textAltschuler, Steven J.. (1991). Singularities of the curve shrinking flow for space curves. Retrieved from the University Digital Conservancy, https://hdl.handle.net/11299/4439
Shortening space curves and flow through singularities
No full textAltschuler, Steven J.; Grayson, Matthew A.. (1991). Shortening space curves and flow through singularities. Retrieved from the University Digital Conservancy, https://hdl.handle.net/11299/4606
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Role of cell identity in growth cone extension during Drosophila visual circuit development
Get PDFThe formation of repeated patterns is a recurring theme during tissue development. Well-studied models include the pigmentation of fish skins, the spacing and orientation of hair follicles, and the connection of sensory neurons. How do seemingly complex, yet highly organized patterns emerge? What rules underlie the development of these cellular patterns? A major challenge is to uncover rules in the face of “biological noise”, arising from stochastic variability of individual cells, local warping of the developing tissue, and specimen-to-specimen differences. Here, I investigated rules governing neuronal pattern formation in the context of Drosophila visual circuit development, where the outer photoreceptors, R1-R6, resort in the lamina layer of the brain to form the stereotyped neural superposition (NSP) circuit. To hunt for signals within the biological noise, I developed a data-driven, standardized coordinate system to characterize the ensemble behaviors of photoreceptors. With this, I was able to identify rules that govern cell-type-specific extension velocities of the photoreceptor pair R3/R4, which uniquely exhibit asymmetric targeting. Specifically, I found that the extension speeds of the R3 and R4 growth cones are inherent to their cell identities. Further, to showcase the predictive power of the coordinate system, I made a computational prediction that extension angles can be explained by a weighted nearest-neighbor repulsion model. My work provides a new case study of how pattern formation rules — hidden within phenotypic variability — can be inferred by quantitative analysis during the development of living organisms
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Non-genetic factors influencing drug persistence and survival in cancer cells
Get PDFDespite the development of new, promising therapies for treating cancer, the emergence of cancer cells that do not respond to treatment remains a major barrier to cure. These emerging populations of cancer cells can result from secondary mutations that give rise to inherited drug tolerance or resistance, but in many cases there is no clear genetic basis for improved drug survival. In fact, prior work has shown that non-genetic mechanisms (e.g. chromatin remodeling) can enable longer-term persistence of cells in drug (Sharma et al., 2010, Hinohara et al., 2018), and we and others have demonstrated that these “persister” cells are an important reservoir for the emergence of drug-resistant mutants (Ramirez et al., 2016, Hata et al., 2016). Here through a combination of data analysis, mathematical modeling, and borrowed insight from microbiology, we further our understanding of non-genetic factors that alter cancer cell response to drug treatment. In the first chapter, I summarize literature describing the persister state in both antibiotic-treated bacteria and drug-treated cancer cells, and I highlight shared features of these persisters (such as slow growth and distinct metabolic activity). Of particular relevance to this dissertation, I discuss epigenetic and metabolic changes that influence cancer progression and drug survival. In the second chapter, I pair a close study of cancer cells differing only by expression of the epigenetic modifier TET2 with mathematical modeling to demonstrate how TET2 loss can confer a fitness advantage in drug by altering the dynamics of cell-state switching. Finally, in the third chapter, I present unpublished work focused on metabolic changes and vulnerabilities associated with TET2 loss. Through these studies, I describe several non-genetic mechanisms that affect persistence and tolerance of cancer cells in drug and highlight the challenges in pharmacologically targeting these complex and ill-defined modes of drug survival
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
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