One critical step in RNA interference (RNAi) experiments is to design small interfering RNAs (siRNAs) that can greatly reduce the expression of the target transcripts, but not of other unintended targets. Although var...
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One critical step in RNA interference (RNAi) experiments is to design small interfering RNAs (siRNAs) that can greatly reduce the expression of the target transcripts, but not of other unintended targets. Although various statistical and computational approaches have been attempted, this remains a challenge facing RNAi researchers. Here, we present a new experimentally validated method for siRNA design. By analyzing public siRNA data and focusing on hyperfunctional siRNAs, we identified a set of sequence features as potency selection criteria to build an siRNA design algorithm with support vector machines. Additional bioinformatics filters were also included in the algorithm to increase RNAi specificity by reducing potential sequence cross-hybridization or microRNA-like effects. Independent validation experiments were performed, which indicated that the newly designed siRNAs have significantly improved performance, and worked effectively even at low concentrations. Furthermore, our cell-based studies demonstrated that the siRNA off-target effects were significantly reduced when the siRNAs were delivered into cells at the 3 nM concentration compared to 30 nM. Thus, the capability of our new design program to select highly potent siRNAs also renders increased RNAi specificity because these siRNAs can be used at a much lower concentration. The siRNA design web server is available at http://***/tools/sidesign/.
The paper extends the result of Harman and Pronzato [Harman, R., Pronzato, L., 2007. Improvements on removing non-optimal support points in D-optimum design algorithms. Statistics & Probability Letters 77, 90-94],...
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The paper extends the result of Harman and Pronzato [Harman, R., Pronzato, L., 2007. Improvements on removing non-optimal support points in D-optimum design algorithms. Statistics & Probability Letters 77, 90-94], which corresponds to p = 0, to all strictly concave criteria in Kiefer's phi(p)-class. We show that, for any given design measure any support point x(*) of a phi(p)-optimal design is such that the directional derivative of phi(p) at xi in the direction of the delta measure at x(*) is larger than some bound h(p) [xi] which is easily computed. (C) 2013 Elsevier B.V. All rights reserved.
A new technique is suggested for the continuous and selective heating of the solid phase in a flowing dispersion. This technique is implemented in a heater-valve-pulsed apparatus unit. Mathematical models are develope...
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A new technique is suggested for the continuous and selective heating of the solid phase in a flowing dispersion. This technique is implemented in a heater-valve-pulsed apparatus unit. Mathematical models are developed for the cocurrent and countercurrent designs of the heater. Analytical solutions are obtained for the model equations, and parameters governing the continuous selective heating of the solid phase are determined. A design algorithm is suggested for the unit.
Abstract—A computer-oriented algorithm for synthesizing combinational logic circuits from a collection of functionally packaged circuits is developed. The algorithm uses a hierarchy of "goals" in an iterati...
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Abstract—A computer-oriented algorithm for synthesizing combinational logic circuits from a collection of functionally packaged circuits is developed. The algorithm uses a hierarchy of "goals" in an iterative decision process in a manner similar to that employed by theorem proving and gamne playing programs. With each iteration a set of "tasks" finds the circuit package which satisfies the highest level goal while meeting circuit constraints.
Necessary and sufficient condition for the stabilizability of linear discrete systems by a static output feedback control are formulated and used in designing algorithms for robust stabilizing controls and controls th...
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Necessary and sufficient condition for the stabilizability of linear discrete systems by a static output feedback control are formulated and used in designing algorithms for robust stabilizing controls and controls that ensure concurrent stabilization of a family of discrete systems. algorithms are implemented by MATLAB and SCILAB with LMISOLVER and SeDuMi interfaces. The results are generalized to random-structure systems.
Calmodulin (CaM) is a second messenger protein that has evolved to bind tightly to a variety of targets and, as such, exhibits low binding specificity. We redesigned CaM by using a computational protein design algorit...
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Calmodulin (CaM) is a second messenger protein that has evolved to bind tightly to a variety of targets and, as such, exhibits low binding specificity. We redesigned CaM by using a computational protein design algorithm to improve its binding specificity for one of its targets, smooth muscle myosin light chain kinase (smMLCK). Residues in or near the CaM/smMLCK binding interface were optimized;CaM interactions with alternative targets were not directly considered in the optimization. The predicted CaM sequences were constructed and tested for binding to a set of eight targets including smMLCK. The best CaM variant, obtained from a calculation that emphasized intermolecular interactions, showed up to a 155-fold increase in binding specificity. The increase in binding specificity was not due to improved binding to smMLCK, but due to decreased binding to the alternative targets. This finding is consistent with the fact that the sequence of wild-type CaM is nearly optimal for interactions with numerous targets.
An approach to designing algorithms for confining constraints within the aircraft control trajectory is elaborated on the basis of geometric transformations in three-dimensional state space. algorithms are designed to...
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An approach to designing algorithms for confining constraints within the aircraft control trajectory is elaborated on the basis of geometric transformations in three-dimensional state space. algorithms are designed to confine the constraints for airborne control complexes and adaptive to the current coordinate-parametric state of the object and configuration of the constraining surface. Formulas for computing the aircraft position angles in space during maneuvers to veer off from the constraining surface are derived. The veer-off trajectory is realized by direct optimization tools and algorithms. An example is given to illustrate to veer off from surface of a paraboloid of rotation.
A design algorithm based on a modified minimizing search technique is applied to design a visible antireflection coating for a wide angular incidence with an angle up to 30degrees from the normal. The design approach ...
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A design algorithm based on a modified minimizing search technique is applied to design a visible antireflection coating for a wide angular incidence with an angle up to 30degrees from the normal. The design approach consisting of tuning and minimizing operations is, effective in refining the antireflective performance and simplifying the design structure of the desired solution. It is shown that the maximum wide angular visible spectral reflectance of minimizing search antireflection coating designs for a three-material 60-layer system is reduced to less than 0.490% with 15-21-layered structures, and the average visible spectral reflectance for each incident angle is reduced to below 0.137%.
Two-dimensional (2-d) cutting components are essential in the Architecture, Engineering, and Construction (AEC) industry. However, due to the complexity of computing cut components' reuse, the 2-d cutting componen...
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Two-dimensional (2-d) cutting components are essential in the Architecture, Engineering, and Construction (AEC) industry. However, due to the complexity of computing cut components' reuse, the 2-d cutting component still lacks appropriate design-aid tools to generate accurate graphical and numerical results in the architectural design process, leading to material waste and hindering the entry of intelligent technologies. This research proposed a grid-based planning workflow based on the BIM and parametric design (PD) to accurately generate and optimize 2d cutting components' planning. The proposed workflow combined the "2-d bin packing problem" problem-solving method in operations research to compute the components' reuse. Moreover, an evolutionary algorithm was used to enable the workflow can goal-oriented optimize the design alternatives according to requirements, expanding the workflow's adaptability. A prototype system was developed to verify the proposed workflow. The results show that compared with current design-aid approaches, the proposed workflow can generate accurate graphical and numerical results while reducing material waste by 7%-12% due to the refined design. The outcomes improve the intelligence of the AEC industry while promoting the industry's sustainable development.
Many design algorithms can be formulated as determining a set of parameters to satisfy conventional and infinite dimensional constraints. An algorithm, with quadratic rate of convergence, for solving such inequalities...
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Many design algorithms can be formulated as determining a set of parameters to satisfy conventional and infinite dimensional constraints. An algorithm, with quadratic rate of convergence, for solving such inequalities, is presented.
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