scholarly journals A Model for Resource Competition in CRISPR-Mediated Gene Repression

2018 ◽  
Author(s):  
Pin-Yi Chen ◽  
Yili Qian ◽  
Domitilla Del Vecchio

AbstractCRISPR-mediated gene regulation is known for its ability to control multiple targets simultaneously due to its modular nature: the same dCas9 effector can target different genes simply by changing the associated gRNA. However, multiplexing requires the sharing of limited amounts of dCas9 proteins among multiple gRNAs, leading to resource competition. In turn, competition between gRNAs for the same resource may hamper network function. In this work, we develop a general model that takes into account the sharing of a limited amount of dCas9 protein for arbitrary CRISPR-mediated gene repression networks. We demonstrate that, as a result of resource competition, hidden interactions appear, that modify the intended network regulations. As a case study, we analyze the effects of these hidden interactions in repression cascades. In particular, we illustrate that perfect adaptation to resource fluctuations can be achieved in cascades with an even number of repressors. In contrast, cascades with an odd number of repressors are substantially impacted by resource competition.

Author(s):  
Sophia Kalantzakos

In 2010, because of a geopolitical incident between China and Japan, seventeen elements of the periodic table known as rare earths became notorious overnight. An “unofficial” and temporary embargo of rare-earth shipments to Japan alerted the world to China’s near monopoly position on the production and export of these indispensable elements for high-tech, defense, and renewable energy sources. A few months before the geopolitical confrontation, China had chosen to substantially cut export quotas of rare earths. Both events sent shockwaves across the markets, and rare-earth prices skyrocketed, prompting reactions from industrial nations and industry itself. The rare-earth crisis is not a simple trade dispute, however. It also raises questions about China’s use of economic statecraft and the impacts of growing resource competition. A detailed and nuanced examination of the rare-earth crisis provides a significant and distinctive case study of resource competition and its spill-over geopolitical effects. It sheds light on the formulation, deployment, longevity, effectiveness, and, perhaps, shortsightedness of policy responses by other industrial nations, while also providing an example of how China might choose to employ instruments of economic statecraft in its rise to superpower status.


Oikos ◽  
2014 ◽  
Vol 124 (3) ◽  
pp. 319-330 ◽  
Author(s):  
Damaris Zurell ◽  
Ute Eggers ◽  
Michael Kaatz ◽  
Shay Rotics ◽  
Nir Sapir ◽  
...  

2019 ◽  
Vol 6 (1) ◽  
pp. 7-26
Author(s):  
Milan Jaćević

Investigations into the nature of the activity of gaming have been made difficult by virtue of the plurality of possible forms this activity may take. In this paper, I address this problem by examining (digital) gaming under the heading of practice theory, in an attempt to shed more light on the practical aspects of ludic literacy. Building on the theoretical and conceptual frameworks of Pierre Bourdieu, I present a general model of digital gaming as a form of situated human practice, followed by details of a case study, conducted in order to test and adjust the initial version of the model. Though further research with a greater population of players is needed in order to expand the scope of the model, the findings of the study lend credence to its validity as a conceptual framework for delineating and framing different practices generated by digital game artefacts.


2019 ◽  
Vol 214 ◽  
pp. 07029
Author(s):  
David Ojika ◽  
Ann Gordon-Ross ◽  
Herman Lam ◽  
Bhavesh Patel

Field-programmable gate arrays (FPGAs) have largely been used in communication and high-performance computing and given the recent advances in big data and emerging trends in cloud computing (e.g., serverless [18]), FPGAs are increasingly being introduced into these domains (e.g., Microsoft’s datacenters [6] and Amazon Web Services [10]). To address these domains’ processing needs, recent research has focused on using FPGAs to accelerate workloads, ranging from analytics and machine learning to databases and network function virtualization. In this paper, we present an ongoing effort to realize a high-performance FPGA-as-a-microservice (FaaM) architecture for the cloud. We discuss some of the technical challenges and propose several solutions for efficiently integrating FPGAs into virtualized environments. Our case study deploying a multithreaded, multi-user compression as a microservice using the FaaM architecture indicate that microservices-based FPGA acceleration can sustain high-performance compared to straightforward implementation with minimal to no communication overhead despite the hardware abstraction.


2010 ◽  
Vol 21 (9) ◽  
pp. 1462-1469 ◽  
Author(s):  
Michael Johnston ◽  
Marie-Claude Geoffroy ◽  
Andrew Sobala ◽  
Ron Hay ◽  
Gyorgy Hutvagner

Key components of the miRNA-mediated gene regulation pathway are localized in cytoplasmic processing bodies (P-bodies). Mounting evidence suggests that the presence of microscopic P-bodies are not always required for miRNA-mediated gene regulation. Here we have shown that geldanamycin, a well-characterized HSP90 inhibitor, abolishes P-bodies and significantly reduces Argonaute and GW182 protein levels but does not affect the miRNA level and the efficiency of miRNA-mediated gene repression; however, it significantly impairs siRNA loading and the efficacy of exogenous siRNA. Our data suggests that HSP90 protein chaperones Argonautes before binding RNA and may facilitate efficient loading of small RNA.


2018 ◽  
Author(s):  
Chensi Miao ◽  
Huiwei Zhao ◽  
Long Qian ◽  
Chunbo Lou

AbstractWith a unique crRNA processing capability, the CRISPR associated Cpf1 protein holds great potential for multiplex gene regulation. Unlike the well-studied Cas9 protein, however, conversion of Cpf1 to a transcription regulator and its related properties have not been systematically explored yet. In this study, we investigated the mutation schemes and crRNA requirements for the nuclease deactivated Cpf1 (dCpf1). By shortening the direct repeat sequence, we obtained genetically stable crRNA co-transcripts and improved gene repression with multiplex targeting. A screen of diversity-enriched PAM library was designed to investigate the PAM-dependency of gene regulation by dCpf1 from Francisella novicida and Lachnospiraceae bacterium. We found novel PAM patterns that elicited strong or medium gene repressions. Using a computational algorithm, we predicted regulatory outputs for all possible PAM sequences, which spanned a large dynamic range that could be leveraged for regulatory purposes. These newly identified features will facilitate the efficient design of CRISPR-dCpf1 based systems for tunable multiplex gene regulation.


Author(s):  
Davoud Ghahremanlou ◽  
Wieslaw Kubiak

Environmental concerns and energy security have led governments to establish legislations to convertConventional Petroleum Supply Chain (CPSC) to Sustainable Petroleum Supply Chain (SPSC). The United States(US), one of the biggest oil consumers in the world, has created regulations to manage ethanol production and con-sumption for the last half century. Though these regulations have created new opportunities, they have also added newburdens to the obligated parties. It is thus key for the government, the obligated parties, and related businesses to studythe impact of the policies on the SPSC. We develop a two-stage stochastic programming model, General Model (GM),which incorporates Renewable Fuel Standard 2 (RFS2), Tax Credits, Tariffs, and Blend Wall (BW) to study the policyimpact on the SPSC using cellulosic ethanol. The model, as any other general model available in the literature, makesit highly impractical to study the policy impact due to the model’s computational complexity. We use the GM to derivea Lean Model (LM) to study the impact by running computational experiments more efficiently and consequently byarriving at robust managerial insights much faster. We present a case study of the policy impact on the SPSC in theState of Nebraska using the LM in the accompanying part II (Ghahremanlou and Kubiak 2020).


2010 ◽  
Vol 19 (9) ◽  
pp. 2619-2636 ◽  
Author(s):  
Pei Shengji ◽  
Alan C. Hamilton ◽  
Yang Lixin ◽  
Huai Huyin ◽  
Yang Zhiwei ◽  
...  

1992 ◽  
Vol 13 (2) ◽  
pp. 211-228 ◽  
Author(s):  
David Knights ◽  
Fergus Murray

Drawing on case study material, this paper explores the politics of career and resource competition that is a medium and outcome of IT investment strategies and system development priorities. This is achieved by examining the manner in which different managers and operating divisions in the case study organization perceive and pursue distinct IT priorities. This they do by involving particular constructions of 'markets', 'technology', and 'organization'. The paper argues that the difficulties encountered around the development of IT systems in the case study company are symptomatic of tensions which are a condition and conse quence of struggles over resource allocation and career advancement within management. These activities necessarily generate considerable political activity which has potentially painful consequences for actors tied into power/identity relations in the modem organization.


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