Dual periodic event-triggered control for multi-agent systems with input saturation.

This paper is concerned with the periodic event-triggered consensus of multi-agent systems subject to input saturation. Due to the nonlinearity caused by the input saturation constraint, the accuracy of the event-triggered mechanism to screen data will be reduced. To deal with this problem, a novel dual periodic event-triggered mechanism is first proposed, in which a saturation-assisted periodic event-trigger and a complemental periodic event-trigger work synergistically to screen data more efficiently under the input saturation constraint. In addition, considering the various disturbances in the environment, a more general mixed H∞ and passive performance is introduced to describe the disturbance attenuation level. Based on the Lyapunov-Krasovskii functional, some less conservative consensus criteria are obtained for the multi-agent systems. In addition, under different input saturation constraints, the relationship between the disturbance attenuation level and the data transmission rate is explored. After that, a particle swarm optimization algorithm is a first attempt to estimate and enlarge the region of asymptotic consensus. Finally, an example is given to verify the effectiveness and superiority of our proposed method.

Novel Extended State Observer Design for Uncertain Nonlinear Systems via Refined Dynamic Event-Triggered Communication Protocol.

In this article, an extended state observer (ESO) design problem is investigated for uncertain nonlinear systems subject to limited network bandwidth. First, for rational information exchange scheduling, a dynamic event-triggered (DET) communication protocol is proposed. Different from the traditional static event-triggered strategies with fixed thresholds, an internal dynamic variable is introduced to be adaptively adjusted by a dual-directional regulating mechanism. Thus, more desirable tradeoff between observation performance and communication resource efficiency is achieved. Second, inspired by our early work on Takagi-Sugeno fuzzy ESO (TSFESO), a novel paradigm of event-triggered TSFESO is initially proposed. Third, under the DET mechanism, the TSFESO design approach is derived to carry out exponential convergence for estimation error dynamics. Finally, the effectiveness of the proposed method is verified by numerical examples. The nonlinear estimating efficiency and linear numerical tractability are integrated in TSFESO. In addition, a generalized ESO formulation is developed to allow some nonadditive uncertainties incompatible with total disturbance, such as improved event-triggered strategy, and thus, the application sphere of ESO is further expanded.

dGMP Binding to Thymidylate Kinase from Plasmodium falciparum Shows Half-Site Binding and Induces Protein Dynamics at the Dimer Interface.

Plasmodium falciparum thymidylate kinase (PfTMK) is an essential enzyme for the growth of the organism because of its critical role in the de novo synthesis of deoxythymidine 5'-diphosphate (TDP), a precursor for TTP that is required for DNA replication and repair. The kinetics, thermodynamic parameters, and substrate binding properties of PfTMK for TMP, dGMP, ADP, and ATP were measured and characterized by steady-state kinetics and a combination of isothermal titration calorimetry, tryptophan fluorescence titration, and NMR. Mutational studies were performed to investigate residues that contribute to the unique ability of PfTMK to also utilize dGMP as a substrate. Isothermal titration calorimetry experiments revealed that dGMP binding exhibits a unique half-site binding mechanism. The occlusion of the empty site in the dGMP complex is supported by molecular mechanics calculations. Relaxation dispersion experiments show that the dGMP and enzyme complex is more dynamic at the dimer interface than the TMP complex on the µs-ms time scale. The unique properties of dGMP binding need to be considered in the design of guanosine-based PfTMK-specific inhibitors.

Interaction of α-Thymidine Inhibitors with Thymidylate Kinase from Plasmodium falciparum.

Plasmodium falciparum thymidylate kinase (PfTMK) is a critical enzyme in the de novo biosynthesis pathway of pyrimidine nucleotides. N-(5'-Deoxy-α-thymidin-5'-yl)- N'-[4-(2-chlorobenzyloxy)phenyl]urea was developed as an inhibitor of PfTMK and has been reported as an effective inhibitor of P. falciparum growth with an EC50 of 28 nM [Cui, H., et al. (2012) J. Med. Chem. 55, 10948-10957]. Using this compound as a scaffold, a number of derivatives were developed and, along with the original compound, were characterized in terms of their enzyme inhibition ( Ki) and binding affinity ( KD). Furthermore, the binding site of the synthesized compounds was investigated by a combination of mutagenesis and docking simulations. Although the reported compound is indicated to be highly effective in its inhibition of parasite growth, we observed significantly lower binding affinity and weaker inhibition of PfTMK than expected from the reported EC50. This suggests that significant structural optimization will be required for the use of this scaffold as an effective PfTMK inhibitor and that the inhibition of parasite growth is due to an off-target effect.

Design of Bivalent Nucleic Acid Ligands for Recognition of RNA-Repeated Expansion Associated with Huntington's Disease.

We report the development of a new class of nucleic acid ligands that is comprised of Janus bases and the MPγPNA backbone and is capable of binding rCAG repeats in a sequence-specific and selective manner via, inference, bivalent H-bonding interactions. Individually, the interactions between ligands and RNA are weak and transient. However, upon the installation of a C-terminal thioester and an N-terminal cystine and the reduction of disulfide bond, they undergo template-directed native chemical ligation to form concatenated oligomeric products that bind tightly to the RNA template. In the absence of an RNA target, they self-deactivate by undergoing an intramolecular reaction to form cyclic products, rendering them inactive for further binding. The work has implications for the design of ultrashort nucleic acid ligands for targeting rCAG-repeat expansion associated with Huntington's disease and a number of other related neuromuscular and neurodegenerative disorders.