Merlin: Computer-Aided Oligonucleotide Design for Large Scale Genome Engineering with MAGE

2016 ◽  
Vol 5 (6) ◽  
pp. 452-458 ◽  
Author(s):  
Michael Quintin ◽  
Natalie J. Ma ◽  
Samir Ahmed ◽  
Swapnil Bhatia ◽  
Aaron Lewis ◽  
...  
2012 ◽  
Vol 160 (1-2) ◽  
pp. 72-79 ◽  
Author(s):  
Tamás Fehér ◽  
Valerie Burland ◽  
György Pósfai

2019 ◽  
Vol 48 (1) ◽  
pp. 472-485 ◽  
Author(s):  
Felix Lansing ◽  
Maciej Paszkowski-Rogacz ◽  
Lukas Theo Schmitt ◽  
Paul Martin Schneider ◽  
Teresa Rojo Romanos ◽  
...  

Abstract Site-specific recombinases (SSRs) such as the Cre/loxP system are useful genome engineering tools that can be repurposed by altering their DNA-binding specificity. However, SSRs that delete a natural sequence from the human genome have not been reported thus far. Here, we describe the generation of an SSR system that precisely excises a 1.4 kb fragment from the human genome. Through a streamlined process of substrate-linked directed evolution we generated two separate recombinases that, when expressed together, act as a heterodimer to delete a human genomic sequence from chromosome 7. Our data indicates that designer-recombinases can be generated in a manageable timeframe for precision genome editing. A large-scale bioinformatics analysis suggests that around 13% of all human protein-coding genes could be targetable by dual designer-recombinase induced genomic deletion (dDRiGD). We propose that heterospecific designer-recombinases, which work independently of the host DNA repair machinery, represent an efficient and safe alternative to nuclease-based genome editing technologies.


2018 ◽  
Vol 35 (2) ◽  
pp. 1085-1097 ◽  
Author(s):  
Sergey Shevtsov ◽  
Igor V. Zhilyaev ◽  
Ilya Tarasov ◽  
Jiing-Kae Wu ◽  
Natalia G. Snezhina

Purpose The purpose of this paper is to develop the multi-objective optimization approach and its numerical implementation to synthesise the model-base control for the part curing at autoclave processing, which supplies the stability and uniformity of the structure and mechanical properties of the material within the cured composite part. Design/methodology/approach The approach includes conversion of the cured part and mold geometry from their computer-aided design (CAD) to computer-aided engineering (CAE) representation, a finite element (FE) formulation of the coupled forward heat transfer/thermal kinetic problem with the parameters of prepreg, which should be determined by the thermal analysis, and, finally, a mapping of the area of 4D design space (thermal control parameters) to 2D objective space, whose coordinates are the maximum deviations of degree of cure and temperature within the cured part calculated at each call of the FE model. Findings The present modeling and optimization approach to the cure process control of the prepreg with thermosetting resin, as well as the means of visualizing optimization results, allow providing insight into complex curing phenomena, estimating the best achievable quality indicators of manufactured composite parts, finding satisfactory parameters of the control law and deciding considering all manufacturing constraints. Research limitations/implications The research can be effectively used to optimize the cure process control for a wide class of polymeric composite parts, even with a complex geometry, but it requires the exact conversion of the geometry of the modeled part from the CAD to CAE environment, which implies the need for excluding all topological imperfections of original CAD model to eliminate the possible formation of void elements and other reasons that do not allow the correct FE meshing. Because thermal, rheological and kinetics parameters, which include the governing equations of cure process, depend on the reinforcing fibers, and especially on the resin properties, the thermal testing for the new modeled prepreg needs to be performed. Practical implications Computer implementation of the proposed approach and numerical method for model-based optimal control synthesis for composite part cure process can be used in aircraft, rotorcraft, ship and automotive technologies at the design of manufacturing process of the large composite parts with complex shape. Social implications This will allow much better quality for large-scale composite parts, excluding very expensive, time-, energy- and material-consuming multiple cure process testing. Originality/value This is first time the problem of optimal control synthesis for curing the large-scale composite parts of complex shape was solved.


Radiology ◽  
1999 ◽  
Vol 213 (3) ◽  
pp. 723-726 ◽  
Author(s):  
Heber MacMahon ◽  
Roger Engelmann ◽  
Fred M. Behlen ◽  
Kenneth R. Hoffmann ◽  
Takayuki Ishida ◽  
...  

2014 ◽  
Vol 590 ◽  
pp. 916-919
Author(s):  
Yan Juan Huo

As the flourishing of computer technology and the appearing of lots of large-scale and well-designed corpora and concordance software, corpus-based approach, an advanced teaching resources, has been widely employed in language researches of various fields and perspectives. English teaching material, the main source of language input, has the quality and authority in Chinese English language teaching classes. The present study attempts to bring about some innovations in construction and designing of teaching material on the basis of the Corpus of Contemporary American English (COCA). Moreover, the research is intended to effectively improve teacher’s input and introducing data-driven learning (DDL), and to effectively stimulate the motivations of students by using this computer-aided and COCA-based designing.


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