Direct Injection of CRISPR/Cas9-Related mRNA into Cytoplasm of Parthenogenetically Activated Porcine Oocytes Causes Frequent Mosaicism for Indel Mutations

Some reports demonstrated successful genome editing in pigs by one-step zygote microinjection of mRNA of CRISPR/Cas9-related components. Given the relatively long gestation periods and the high cost of housing, the establishment of a single blastocyst-based assay for rapid optimization of the above system is required. As a proof-of-concept, we attempted to disrupt a gene (GGTA1) encoding the α-1,3-galactosyltransferase that synthesizes the α-Gal epitope using parthenogenetically activated porcine oocytes. The lack of α-Gal epitope expression can be monitored by staining with fluorescently labeled isolectin BS-I-B₄ (IB4), which binds specifically to the α-Gal epitope. When oocytes were injected with guide RNA specific to GGTA1 together with enhanced green fluorescent protein (EGFP) and human Cas9 mRNAs, 65% (24/37) of the developing blastocysts exhibited green fluorescence, although almost all (96%, 23/24) showed a mosaic fluorescent pattern. Staining with IB4 revealed that the green fluorescent area often had a reduced binding activity to IB4. Of the 16 samples tested, six (five fluorescent and one non-fluorescent blastocysts) had indel mutations, suggesting a correlation between EGFP expression and mutation induction. Furthermore, it is suggested that zygote microinjection of mRNAs might lead to the production of piglets with cells harboring various mutation types.     

Glibenclamide for the Treatment of Ischemic and Hemorrhagic Stroke

Ischemic and hemorrhagic strokes are associated with severe functional disability and high mortality. Except for recombinant tissue plasminogen activator, therapies targeting the underlying pathophysiology of central nervous system (CNS) ischemia and hemorrhage are strikingly lacking. Sur1-regulated channels play essential roles in necrotic cell death and cerebral edema following ischemic insults, and in neuroinflammation after hemorrhagic injuries. Inhibiting endothelial, neuronal, astrocytic and oligodendroglial sulfonylurea receptor 1–transient receptor potential melastatin 4 (Sur1–Trpm4) channels and, in some cases, microglial K_ATP (Sur1–Kir6.2) channels, with glibenclamide is protective in a variety of contexts. Robust preclinical studies have shown that glibenclamide and other sulfonylurea agents reduce infarct volumes, edema and hemorrhagic conversion, and improve outcomes in rodent models of ischemic stroke. Retrospective studies suggest that diabetic patients on sulfonylurea drugs at stroke presentation fare better if they continue on drug. Additional laboratory investigations have implicated Sur1 in the pathophysiology of hemorrhagic CNS insults. In clinically relevant models of subarachnoid hemorrhage, glibenclamide reduces adverse neuroinflammatory and behavioral outcomes. Here, we provide an overview of the preclinical studies of glibenclamide therapy for CNS ischemia and hemorrhage, discuss the available data from clinical investigations, and conclude with promising preclinical results that suggest glibenclamide may be an effective therapeutic option for ischemic and hemorrhagic stroke.     

Fully coupled LES-DEM of particle interaction and agglomeration in a turbulent channel flow

Coupled large eddy simulation and the discrete element method are applied to study turbulent particle–laden flows, including particle dispersion and agglomeration, in a channel. The particle–particle interaction model is based on the Hertz–Mindlin approach with Johnson–Kendall–Roberts cohesion to allow the simulation of van der Waals forces in a dry air flow. The influence of different particle surface energies, and the impact of fluid turbulence, on agglomeration behaviour are investigated. The agglomeration rate is found to be strongly influenced by the particle surface energy, with a positive relationship observed between the two. Particle agglomeration is found to be enhanced in two separate regions within the channel. First, in the near-wall region due to the high particle concentration there driven by turbophoresis, and secondly in the buffer region where the high turbulence intensity enhances particle–particle interactions.     

Model checking temporal knowledge and commitments in multi-agent systems using reduction

Though modeling and verifying Multi-Agent Systems (MASs) have long been under study, there are still challenges when many different aspects need to be considered simultaneously. In fact, various frameworks have been carried out for modeling and verifying MASs with respect to knowledge and social commitments independently. However, considering them under the same framework still needs further investigation, particularly from the verification perspective. In this article, we present a new technique for model checking the logic of knowledge and commitments (CTLKC⁺). The proposed technique is fully-automatic and reduction-based in which we transform the problem of model checking CTLKC⁺ into the problem of model checking an existing logic of action called ARCTL. Concretely, we construct a set of transformation rules to formally reduce the CTLKC⁺ model into an ARCTL model and CTLKC⁺ formulae into ARCTL formulae to get benefit from the extended version of NuSMV symbolic model checker of ARCTL. Compared to a recent approach that reduces the problem of model checking CTLKC⁺ to another logic of action called GCTL¹, our technique has better scalability and efficiency. We also analyze the complexity of the proposed model checking technique. The results of this analysis reveal that the complexity of our reduction-based procedure is PSPACE-complete for local concurrent programs with respect to the size of these programs and the length of the formula being checked. From the time perspective, we prove that the complexity of the proposed approach is P-complete with regard to the size of the model and length of the formula, which makes it efficient. Finally, we implement our model checking approach on top of extended NuSMV and report verification results for the verification of the NetBill protocol, taken from business domain, against some desirable properties. The obtained results show the effectiveness of our model checking approach when the system scales up.     

R-curves determination of ordinary refractory ceramics assisted by digital image correlation method

As a figure-of-merit, the rising ratio of crack propagation resistance to fracture initiation resistance indicates a reduction of the brittleness and enhances the thermal shock resistance of ordinary refractory ceramics. The significant nonlinear fracture behaviour is related to the development of a fracture process zone (FPZ). The universal dimensionless load–displacement diagram method is applied as a promising graphical method for the determination of R-curves for magnesia refractories showing different brittleness. By applying digital image correlation (DIC) together with the graphical method, the problems arisen with accurate determination of the fracture initiation resistance and the crack length are overcome. Meanwhile, the R-curve is subdivided with respect to the fracture processes, viz the fracture initiation, the development of FPZ and the onset of traction free macro-crack. With the simultaneous crack lengths evaluated from DIC, the contribution of each fracture process to the crack propagation resistance at certain loading stage is quantitatively presented.     

Adaptive actuator failure compensation design for unknown chaotic multi‐input systems

In this paper, an adaptive control approach is designed for compensating the faults in the actuators of chaotic systems and maintaining the acceptable system stability. We propose a state‐feedback model reference adaptive control scheme for unknown chaotic multi‐input systems. Only the dimensions of the chaotic systems are required to be known. Based on Lyapunov stability theory, new adaptive control laws are synthesized to accommodate actuator failures and system nonlinearities. An illustrative example is studied. The simulation results show the effectiveness of the design method. Copyright © 2014 John Wiley & Sons, Ltd.     

Elitist clonal selection algorithm for optimal choice of free knots in B-spline data fitting

Data fitting with B-splines is a challenging problem in reverse engineering for CAD/CAM, virtual reality, data visualization, and many other fields. It is well-known that the fitting improves greatly if knots are considered as free variables. This leads, however, to a very difficult multimodal and multivariate continuous nonlinear optimization problem, the so-called knot adjustment problem. In this context, the present paper introduces an adapted elitist clonal selection algorithm for automatic knot adjustment of B-spline curves. Given a set of noisy data points, our method determines the number and location of knots automatically in order to obtain an extremely accurate fitting of data. In addition, our method minimizes the number of parameters required for this task. Our approach performs very well and in a fully automatic way even for the cases of underlying functions requiring identical multiple knots, such as functions with discontinuities and cusps. To evaluate its performance, it has been applied to three challenging test functions, and results have been compared with those from other alternative methods based on AIS and genetic algorithms. Our experimental results show that our proposal outperforms previous approaches in terms of accuracy and flexibility. Some other issues such as the parameter tuning, the complexity of the algorithm, and the CPU runtime are also discussed.     

综放高瓦斯矿井煤层瓦斯涌出量综合预测

为了成功预测竹林山煤矿综放高瓦斯矿井大采高工作面煤层瓦斯涌出量,以主采3号煤层为主要研究对象,针对3号煤层以往开采情况,通过布设测点测量其煤层瓦斯含量和了解相邻矿井瓦斯含量,采用分源预测法、回归法及统计法等预测方法得到了3号煤层瓦斯含量的分布规律,并绘制了3号煤层的瓦斯含量等值线图。对矿井不同生产时期的瓦斯含量进行预测,得到了生产前期、中期及后期采区的最大绝对瓦斯涌出量和最大相对瓦斯涌出量,说明了竹林山煤矿各个时期均属于高瓦斯矿井。     

Controllability and observability of multi-agent systems with heterogeneous and switching topologies

ABSTRACT

This paper focuses on controllability and observability of multi-agent systems with heterogeneous and switching topologies, where the first- and the second-order information interaction topologies are different and switching. First, based on the controllable state set, a controllability criterion is obtained in terms of the controllability matrix corresponding to the switching sequence. Next, by virtue of the subspace sequence, two necessary and sufficient algebraic conditions are established for controllability in terms of the system matrices corresponding to all the possible topologies. Furthermore, controllability is considered from the graphic perspective. It is proved that the system is controllable if the union graph of all the possible topologies is controllable. With respect to observability, two sufficient and necessary conditions are derived by taking advantage of the system matrices and the corresponding invariant subspace, respectively. Finally, some simulation examples are worked out to illustrate the theoretical results.     

A review on some classes of algebraic systems

ABSTRACT

In this paper, we review some algebraic control system. Precisely, linear and bilinear systems on Euclidean spaces and invariant and linear systems on Lie groups. The fourth classes of systems have a common issue: to any class, there exists an associated subgroup. From this object, we survey the controllability property. Especially, from those coming from our contribution to the theory.