The Experts below are selected from a list of 64899 Experts worldwide ranked by ideXlab platform

Ahmet Yildiz - One of the best experts on this subject based on the ideXlab platform.

  • enhanced proofreading governs crispr cas9 Targeting accuracy
    Nature, 2017
    Co-Authors: Janice S Chen, Yavuz S Dagdas, Benjamin P Kleinstiver, Moira M Welch, Alexander A Sousa, Lucas B Harrington, Samuel H Sternberg, Keith J Joung, Ahmet Yildiz
    Abstract:

    A new engineered version of SpCas9, called HypaCas9, displays enhanced accuracy of editing without significant loss of efficiency at the Desired Target.

  • enhanced proofreading governs crispr cas9 Targeting accuracy
    Nature, 2017
    Co-Authors: Janice S Chen, Yavuz S Dagdas, Benjamin P Kleinstiver, Moira M Welch, Alexander A Sousa, Lucas B Harrington, Samuel H Sternberg, Keith J Joung, Ahmet Yildiz
    Abstract:

    A new engineered version of SpCas9, called HypaCas9, displays enhanced accuracy of editing without significant loss of efficiency at the Desired Target. One of the main concerns about the use of CRISPR in genomic editing is the possibility of 'off-Target' events. Scientists have been modifying the central enzyme involved in CRISPR editing, Cas9 or its homologues, to reduce this unwanted property. Jennifer Doudna and colleagues describe a new version of this nuclease, HypaCas9, which enables more accurate editing, without substantial loss of efficiency on the Desired Target. The RNA-guided CRISPR–Cas9 nuclease from Streptococcus pyogenes (SpCas9) has been widely repurposed for genome editing1,2,3,4. High-fidelity (SpCas9-HF1) and enhanced specificity (eSpCas9(1.1)) variants exhibit substantially reduced off-Target cleavage in human cells, but the mechanism of Target discrimination and the potential to further improve fidelity are unknown5,6,7,8,9. Here, using single-molecule Forster resonance energy transfer experiments, we show that both SpCas9-HF1 and eSpCas9(1.1) are trapped in an inactive state10 when bound to mismatched Targets. We find that a non-catalytic domain within Cas9, REC3, recognizes Target complementarity and governs the HNH nuclease to regulate overall catalytic competence. Exploiting this observation, we design a new hyper-accurate Cas9 variant (HypaCas9) that demonstrates high genome-wide specificity without compromising on-Target activity in human cells. These results offer a more comprehensive model to rationalize and modify the balance between Target recognition and nuclease activation for precision genome editing.

Samuel H Sternberg - One of the best experts on this subject based on the ideXlab platform.

  • enhanced proofreading governs crispr cas9 Targeting accuracy
    Nature, 2017
    Co-Authors: Janice S Chen, Yavuz S Dagdas, Benjamin P Kleinstiver, Moira M Welch, Alexander A Sousa, Lucas B Harrington, Samuel H Sternberg, Keith J Joung, Ahmet Yildiz
    Abstract:

    A new engineered version of SpCas9, called HypaCas9, displays enhanced accuracy of editing without significant loss of efficiency at the Desired Target.

  • enhanced proofreading governs crispr cas9 Targeting accuracy
    Nature, 2017
    Co-Authors: Janice S Chen, Yavuz S Dagdas, Benjamin P Kleinstiver, Moira M Welch, Alexander A Sousa, Lucas B Harrington, Samuel H Sternberg, Keith J Joung, Ahmet Yildiz
    Abstract:

    A new engineered version of SpCas9, called HypaCas9, displays enhanced accuracy of editing without significant loss of efficiency at the Desired Target. One of the main concerns about the use of CRISPR in genomic editing is the possibility of 'off-Target' events. Scientists have been modifying the central enzyme involved in CRISPR editing, Cas9 or its homologues, to reduce this unwanted property. Jennifer Doudna and colleagues describe a new version of this nuclease, HypaCas9, which enables more accurate editing, without substantial loss of efficiency on the Desired Target. The RNA-guided CRISPR–Cas9 nuclease from Streptococcus pyogenes (SpCas9) has been widely repurposed for genome editing1,2,3,4. High-fidelity (SpCas9-HF1) and enhanced specificity (eSpCas9(1.1)) variants exhibit substantially reduced off-Target cleavage in human cells, but the mechanism of Target discrimination and the potential to further improve fidelity are unknown5,6,7,8,9. Here, using single-molecule Forster resonance energy transfer experiments, we show that both SpCas9-HF1 and eSpCas9(1.1) are trapped in an inactive state10 when bound to mismatched Targets. We find that a non-catalytic domain within Cas9, REC3, recognizes Target complementarity and governs the HNH nuclease to regulate overall catalytic competence. Exploiting this observation, we design a new hyper-accurate Cas9 variant (HypaCas9) that demonstrates high genome-wide specificity without compromising on-Target activity in human cells. These results offer a more comprehensive model to rationalize and modify the balance between Target recognition and nuclease activation for precision genome editing.

Bo Liu - One of the best experts on this subject based on the ideXlab platform.

  • optimal Targeting of nonlinear chaotic systems using a novel evolutionary computing strategy
    Knowledge Based Systems, 2016
    Co-Authors: Yudong Wang, Xiaoyi Feng, Xin Lyu, Bo Liu
    Abstract:

    Control of chaotic systems is formulated as constrained optimization problem.Teaching-learning-based optimization is to direct the chaotic series.The efficacy of TLBO based optimal control technique have been demonstrated. Control of chaotic systems to given Targets is a subject of substantial and well-developed research issue in nonlinear science, which can be formulated as a class of multi-modal constrained numerical optimization problem with multi-dimensional decision variables. This investigation elucidates the feasibility of applying a novel population-based metaheuristics labeled here as Teaching-learning-based optimization to direct the orbits of discrete chaotic dynamical systems towards the Desired Target region. Several consecutive control steps of small bounded perturbations are made in the Teaching-learning-based optimization strategy to direct the chaotic series towards the optimal neighborhood of the Desired Target rapidly, where a conventional controller is effective for chaos control. Working with the dynamics of the well-known Henon as well as Ushio discrete chaotic systems, we assess the effectiveness and efficiency of the Teaching-learning-based optimization based optimal control technique, meanwhile the impacts of the core parameters on performances are also discussed. Furthermore, possible engineering applications of directing chaotic orbits are discussed.

  • optimal Targeting of nonlinear chaotic systems using a novel evolutionary computing strategy
    arXiv: Optimization and Control, 2016
    Co-Authors: Yudong Wang, Xiaoyi Feng, Xin Lyu, Bo Liu
    Abstract:

    Control of chaotic systems to given Targets is a subject of substantial and well-developed research issue in nonlinear science, which can be formulated as a class of multi-modal constrained numerical optimization problem with multi-dimensional decision variables. This investigation elucidates the feasibility of applying a novel population-based metaheuristics labelled here as Teaching-learning-based optimization to direct the orbits of discrete chaotic dynamical systems towards the Desired Target region. Several consecutive control steps of small bounded perturbations are made in the Teaching-learning-based optimization strategy to direct the chaotic series towards the optimal neighborhood of the Desired Target rapidly, where a conventional controller is effective for chaos control. Working with the dynamics of the well-known Henon as well as Ushio discrete chaotic systems, we assess the effectiveness and efficiency of the Teaching-learning-based optimization based optimal control technique, meanwhile the impacts of the core parameters on performances are also discussed. Furthermore, possible engineering applications of directing chaotic orbits are discussed.

Janice S Chen - One of the best experts on this subject based on the ideXlab platform.

  • enhanced proofreading governs crispr cas9 Targeting accuracy
    Nature, 2017
    Co-Authors: Janice S Chen, Yavuz S Dagdas, Benjamin P Kleinstiver, Moira M Welch, Alexander A Sousa, Lucas B Harrington, Samuel H Sternberg, Keith J Joung, Ahmet Yildiz
    Abstract:

    A new engineered version of SpCas9, called HypaCas9, displays enhanced accuracy of editing without significant loss of efficiency at the Desired Target.

  • enhanced proofreading governs crispr cas9 Targeting accuracy
    Nature, 2017
    Co-Authors: Janice S Chen, Yavuz S Dagdas, Benjamin P Kleinstiver, Moira M Welch, Alexander A Sousa, Lucas B Harrington, Samuel H Sternberg, Keith J Joung, Ahmet Yildiz
    Abstract:

    A new engineered version of SpCas9, called HypaCas9, displays enhanced accuracy of editing without significant loss of efficiency at the Desired Target. One of the main concerns about the use of CRISPR in genomic editing is the possibility of 'off-Target' events. Scientists have been modifying the central enzyme involved in CRISPR editing, Cas9 or its homologues, to reduce this unwanted property. Jennifer Doudna and colleagues describe a new version of this nuclease, HypaCas9, which enables more accurate editing, without substantial loss of efficiency on the Desired Target. The RNA-guided CRISPR–Cas9 nuclease from Streptococcus pyogenes (SpCas9) has been widely repurposed for genome editing1,2,3,4. High-fidelity (SpCas9-HF1) and enhanced specificity (eSpCas9(1.1)) variants exhibit substantially reduced off-Target cleavage in human cells, but the mechanism of Target discrimination and the potential to further improve fidelity are unknown5,6,7,8,9. Here, using single-molecule Forster resonance energy transfer experiments, we show that both SpCas9-HF1 and eSpCas9(1.1) are trapped in an inactive state10 when bound to mismatched Targets. We find that a non-catalytic domain within Cas9, REC3, recognizes Target complementarity and governs the HNH nuclease to regulate overall catalytic competence. Exploiting this observation, we design a new hyper-accurate Cas9 variant (HypaCas9) that demonstrates high genome-wide specificity without compromising on-Target activity in human cells. These results offer a more comprehensive model to rationalize and modify the balance between Target recognition and nuclease activation for precision genome editing.

Bruce Francis - One of the best experts on this subject based on the ideXlab platform.

  • Geometric Analysis of the Formation Problem for Autonomous Robots
    IEEE Transactions on Automatic Control, 2010
    Co-Authors: Florian Dorfler, Bruce Francis
    Abstract:

    In the formation control problem for autonomous robots, a distributed control law steers the robots to the Desired Target formation. A local stability result of the Target formation can be derived by methods of linearization and center manifold theory or via a Lyapunov-based approach. Besides the Target formation, the closed-loop dynamics of the robots feature various other unDesired invariant sets such as nonrigid formations. This note addresses a global stability analysis of the closed-loop formation control dynamics. We pursue a differential geometric approach and derive purely algebraic conditions for local stability of invariant embedded submanifolds. These theoretical results are then applied to the well-known example of a cyclic triangular formation and result in instability of all invariant sets other than the Target formation.