scholarly journals Interpretable and tractable models of transcriptional noise for the rational design of single-molecule quantification experiments

2021 ◽  
Author(s):  
Gennady Gorin ◽  
John J. Vastola ◽  
Meichen Fang ◽  
Lior Pachter

To what extent do cell-to-cell differences in transcription rate affect RNA copy number distributions, and what can this variation tell us about biological processes underlying transcription? We argue that successfully answering such questions requires quantitative models that are both interpretable (describing concrete biophysical phenomena) and tractable (amenable to mathematical analysis); in particular, such models enable the identification of experiments which best discriminate between competing hypotheses. As a proof of principle, we introduce a simple but flexible class of models involving a stochastic transcription rate (governed by a stochastic differential equation) coupled to a discrete stochastic RNA transcription and splicing process, and compare and contrast two biologically plausible hypotheses about observed transcription rate variation. One hypothesis assumes transcription rate variation is due to DNA experiencing mechanical strain and relaxation, while the other assumes that variation is due to fluctuations in the number of an abundant regulator. Through a thorough mathematical analysis, we show that these two models are challenging to distinguish: properties like first- and second-order moments, autocorrelations, and several limiting distributions are shared. However, our analysis also points to the experiments which best discriminate between them. Our work illustrates the importance of theory-guided data collection in general, and multimodal single-molecule data in particular for distinguishing between competing hypotheses. We use this theoretical case study to introduce and motivate a general framework for constructing and solving such nontrivial continuous-discrete models.

Public Voices ◽  
2016 ◽  
Vol 11 (1) ◽  
pp. 89
Author(s):  
Amy Probsdorfer Kelley ◽  
John C. Morris

The process to win approval to build a national memorial on the National Mall inWashington, DC is both long and complex. Many memorials are proposed, but few are chosen to inhabit the increasingly scarce space available on the Mall. Through the use of network analysis we compare and contrast two memorial proposals, with an eye toward understanding why one proposal was successful while the other seems to have failed. We conclude that the success of a specific memorial has less to do with the perceived popularity of the person or event to be memorialized, and more to do with how the sponsors use the network of people and resources available to advocate for a given proposal.


2015 ◽  
Vol 4 (1) ◽  
pp. 74-86
Author(s):  
Paul Custance ◽  
Keith Walley ◽  
Gaynor Tate ◽  
Goksel Armagan

The purpose of the article is to provide insight into care farming and the role that it may play in agriltural multifunctionality. The paper outlines three case studies of care farming in the UK to compare and contrast the roles that such organizations may play in multifunctional agriculture. Although the work has the obvious limitation of being based on case-study care farms that are based in the UK, the findings are sufficiently generic to serve as valuable learning material for those interested in the subject and located anywhere in the world. The main finding from this study is that care farming can take many different forms but still contribute to agricultural multifunctionality. The study also confirms the important roles that economic support and favourable legislation play in successful care farming. The paper concludes that care farming is a legitimate form of agricultural multifunctionality but reminds those interested in setting up or promoting care farms of the need for a supportive economic and legislative environment. The paper provides contemporary insight into the concept of care farming as a form of agricultural multifunctionality. A number of generic points are made that should be of value to an international audience of academics researching in this area as well as students studying care farming and agricultural multifunctionality, farmers considering diversifying into care farming and politicians working to create a political and economic environment that may support care farms.


2021 ◽  
pp. 001312452110275
Author(s):  
Meredith R. Naughton

This qualitative case study explored the unique ways recent college graduates serving as full-time, near-peer mentors supported students along the path to college in three different urban public high schools. By applying the theory of figured worlds to school spaces and practices, this study sought to both define the physical and figurative ways mentors helped students envision and enact college-bound identities and compare and contrast the differences in these spaces across schools. Data and thematic analysis indicate that promoting the development and enactment of college-bound identities requires intentionality about how school culture, people, and policies enable real and figurative spaces for college-bound exploration and support.


2017 ◽  
Vol 19 (2) ◽  
pp. 304-319 ◽  
Author(s):  
Manfred Elsig

This article asks why the dispute settlement provisions of the multilateral trading system underwent significant reforms during the negotiations that led to the creation of the World Trade Organization (WTO) in 1995. Why did the leading trading powers accept a highly legalized system that departed from established political–diplomatic forms of settling disputes? The contribution of this article is threefold. First, it complements existing accounts that exclusively focus on the United States with a novel explanation that takes account of contextual factors. Second, it offers an in-depth empirical case study based on interviews with negotiators who were involved and novel archival evidence on the creation of the new WTO dispute settlement system. Third, by unpacking the long-standing puzzle of why states designed a highly legalized system, it addresses selected blind spots of the legalization and the rational design literatures with the aim of providing a better understanding about potential paths leading toward significant changes in legalization.


2021 ◽  
pp. 004728752110247
Author(s):  
Vinh Bui ◽  
Ali Reza Alaei ◽  
Huy Quan Vu ◽  
Gang Li ◽  
Rob Law

Understanding and being able to measure, analyze, compare, and contrast the image of a tourism destination, also known as tourism destination image (TDI), is critical in tourism management and destination marketing. Although various methodologies have been developed, a consistent, reliable, and scalable method for measuring TDI is still unavailable. This study aims to address the challenge by proposing a framework for a holistic measure of TDI in four dimensions, including popularity, sentiment, time, and location. A structural model for TDI measurement that covers various aspects of a tourism destination is developed. TDI is then measured by a comprehensive computational framework that can analyze complex textual and visual data on a large scale. A case study using more than 30,000 images, and 10,000 comments in relation to three tourism destinations in Australia demonstrates the effectiveness of the proposed framework.


Author(s):  
Jaroslav Smutny ◽  
Viktor Nohal ◽  
Daniela Vukusicova ◽  
Herbert Seelmann

This paper deals with description and application of the Wigner-Ville transformation for vibration analysis. This transformation belongs to the group of non-linear time-frequency processes. Thanks to its properties, it may be successfully used in the area of non-stationary and transitional signals describing various natural processes. The use in the field of the railway constructions testing represents a quite an interesting application area of the transformation. This paper contains mathematical analysis of the transformation, a case study and practical experience obtained and recommendations for its practical use.


Author(s):  
Nadezhda Shamova ◽  

A broad scope of application of corpus technologies indicates their importance in applied linguistics. Employing the comparative-contrastive method and the method of computer analysis, the author seeks to compare and contrast the main corpus tools of the programs Sketch Engine, AntConc, and WordSmith Tools, focusing on texts from specialized periodicals about cinematography ‘Total Film’ and ‘American Cinematographer’ for 2019–2020. The primary goal of this comparison is to provide recommendations for optimal choice of tools and programs for obtaining certain types of information. The author processed the total volume of texts that contained over 900,000 words, using the functions “concordance”, “word list”, “collocations” + “word s etch”, “N-grams”, “keywords” in Sketch Engine and AntConc (Word-Smith Tools has only “concordance”, “wordlist,” and “keywords”). Information about specific tools available in various corpora is collected and presented in a specially developed table. Different software programs described in the article have functions that perform the same tasks, but there are some differences in how data is presented. Among the software programs featured in this case study, the Sketch Engine platform gives the most options for choosing personal settings. The “concordance” function shows the word in context, “Wordlist” shows all the words on a given list with a record of their frequency in the corpus. The “collocation” function (or “word s etch”) recognizes fixed expressions, “N-grams” finds phrases that comprise a certain number of elements, while the “ eywords” function allows users to identify words that are specific to a particular subject area. Information thus obtained from the corpora may be helpful in updating English LSP dictionaries and glossaries of cinematography. The theoretical significance of the present study lies in systematizing the material about existing corpus tools, while its practical value is in using the tools of three corpus programs for the study of cinematic discourse, understood here as language used by the community of movie goers and filmmakers in their discussions of cinematography in specialized periodicals ‘Total Film’ and ‘American Cinematographer’.


2020 ◽  
Author(s):  
Anirban Das ◽  
Anju Yadav ◽  
Mona Gupta ◽  
R Purushotham ◽  
Vishram L. Terse ◽  
...  

AbstractProtein folding can go wrong in vivo and in vitro, with significant consequences for the living cell and the pharmaceutical industry, respectively. Here we propose a general design principle for constructing small peptide-based protein-specific folding modifiers. We construct a ‘xenonucleus’, which is a pre-folded peptide that resembles the folding nucleus of a protein, and demonstrate its activity on the folding of ubiquitin. Using stopped-flow kinetics, NMR spectroscopy, Förster Resonance Energy transfer, single-molecule force measurements, and molecular dynamics simulations, we show that the ubiquitin xenonucleus can act as an effective decoy for the native folding nucleus. It can make the refolding faster by 33 ± 5% at 3 M GdnHCl. In principle, our approach provides a general method for constructing specific, genetically encodable, folding modifiers for any protein which has a well-defined contiguous folding nucleus.


2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Mukhil Raveendran ◽  
Andrew J. Lee ◽  
Rajan Sharma ◽  
Christoph Wälti ◽  
Paolo Actis

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Debadrita Paria ◽  
Chi Zhang ◽  
Ishan Barman

Abstract In biology, sensing is a major driver of discovery. A principal challenge is to create a palette of probes that offer near single-molecule sensitivity and simultaneously enable multiplexed sensing and imaging in the “tissue-transparent” near-infrared region. Surface-enhanced Raman scattering and metal-enhanced fluorescence have shown substantial promise in addressing this need. Here, we theorize a rational design and optimization strategy to generate nanostructured probes that combine distinct plasmonic materials sandwiching a dielectric layer in a multilayer core shell configuration. The lower energy resonance peak in this multi-resonant construct is found to be highly tunable from visible to the near-IR region. Such a configuration also allows substantially higher near-field enhancement, compared to a classical core-shell nanoparticle that possesses a single metallic shell, by exploiting the differential coupling between the two core-shell interfaces. Combining such structures in a dimer configuration, which remains largely unexplored at this time, offers significant opportunities not only for near-field enhancement but also for multiplexed sensing via the (otherwise unavailable) higher order resonance modes. Together, these theoretical calculations open the door for employing such hybrid multi-layered structures, which combine facile spectral tunability with ultrahigh sensitivity, for biomolecular sensing.


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