1,720,957 research outputs found
Loading as a design parameter for genetic circuits
Full text linkA significant problem when building complex biomolecular circuits is due to context-dependence: the dynamics of a system are altered upon changes to its context, potentially degrading the system's performance. Here, we study retroactivity, a specific type of context-dependence, by analyzing the effects of loads on a transcription factor applied by the transcription factor's target sites. In particular, we study this loading effect on the model of an activator-repressor oscillator, a widely studied motif in synthetic and systems biology. Our analysis indicates that strong activation and weak repression are key for a stable limit cycle. Repression can be effectively weakened by adding load to the repressor, while activation can be effectively weakened by adding load to the activator. Therefore, loading the repressor can be employed as a design parameter to establish a stable limit cycle. In contrast, loading the activator is deleterious to the clock
Cell fate reprogramming using transcription factor feedback overexpression
No full textThesis: M. Eng., Massachusetts Institute of Technology, Department of Mechanical Engineering, 2018.Cataloged from PDF version of thesis.Includes bibliographical references (pages 63-67).Recent advances in stem cell research has demonstrated that the fate of a terminally differentiated cell can be reverted back to pluripotency. The ability to reprogram a differentiated cell back to its undifferentiated, pluripotent state would be a significant breakthrough for regenerative medicine. For example, lost or damaged cells could be replaced by patient-specific reprogrammed cells, thus providing on-demand, compatible, high-quality cells of any required type. However, current protocols for reprogramming rely on simplified models that do not wholly capture system dynamics and on inefficient transcription factor overexpression. We study a gene regulatory network that determines the cell fate in the hematopoietic lineage and demonstrate that a deterministic model cannot capture the experimentally observed system dynamics. We also propose the use of feedback control to address inefficient reprogramming and implement two configurations of the controller on both deterministic and stochastic models of the Oct4-Nanog network. We also address practical issues such as placement of the regulator and consider the effect of inducing or constitutively producing microRNA on the protein steady-state distribution.by Nithin Senthur Kumar.M. Eng
Loading as a design parameter for genetic circuits
No full textThesis: S.M., Massachusetts Institute of Technology, Department of Mechanical Engineering, 2016.Cataloged from PDF version of thesis.Includes bibliographical references (pages 75-78).Since the 2000s, there have been several forms of synthetic genetic circuits that have been modeled and experimentally validated. Examples include the toggle switch, repressilator, various configurations of oscillators, and even logic gates. A major goal in synthetic biology is to combine these modules to construct complex circuits for applications including biosensing, biofuel technology, and various medical technologies. However, a significant problem when building complex biomolecular circuits is due to context-dependence: the dynamics of a system are altered upon changes to its context, potentially degrading the system's performance. In this thesis, we study retroactivity, a specific type of context-dependence, by analyzing the effects of loads on a transcription factor applied by the transcription factor's target sites. In particular, we study this loading effect on the model of an activator-repressor oscillator, a widely studied motif in systems and systems biology. Our analysis indicates that strong activation and weak repression are key for a stable limit cycle. Repression can be effectively weakened by adding load to the repressor, while activation can be effectively weakened by adding load to the activator. Therefore, loading the repressor can be employed as a design parameter to establish a stable limit cycle. In contrast, loading the activator is deleterious to the clock. Experimental protocol and preliminary data are presented. The results presented in this thesis may be helpful to provide a method to tune the dynamics of synthetic genetic circuits without using tags and modifying promoter regions.by Nithin Senthur Kumar.S.M
Deterministic model derivation and model reduction of an activator-repressor genetic oscillator
No full textNIH P50 GM09879
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
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
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