Motion Synchronization For Semi-Autonomous Robotic Swarm With A Passivity-Short Human Operator

This paper investigates coordination between a human operator and robotic swarm. The objective is to guarantee human-enabled motion synchronization to desired position/velocity references. The presence of a human in the system could improve performance in completing complex missions and adaptation to changes in environment or mission goal. Although in some works the human is modeled or assumed as a passive system, this does not always hold and a systematic solution to deal with non-passive humans is still needed. To this end, this paper assumes the human operator’s process as a passivity-short system. Based on the positive feedback interconnection of passivity-short systems, we present a novel distributed control architecture interconnecting the human operator and the robotic swarm. The control goals are then proved to be achieved even in the presence of passivity shortage in the human operator. We finally demonstrate the proposed architecture through simulation studies and also implementation on an experimental testbed

[3<i>a</i>,4]-Dihydropyrazolo[1,5<i>a</i>]pyrimidines: Novel, Potent, and Selective Phosphatidylinositol-3-kinase β Inhibitors

A series of novel [3<i>a</i>,4]­dihydropyrazolo­[1,5<i>a</i>]­pyrimidines were identified, which were highly potent and selective inhibitors of PI3Kβ. The template afforded the opportunity to develop novel SAR for both the hinge-binding (R₃) and back-pocket (R₄) substitutents. While cellular potency was relatively modest due to high protein binding, the series displayed low clearance in rat, mouse, and monkey

Rational Design, Synthesis, and SAR of a Novel Thiazolopyrimidinone Series of Selective PI3K-beta Inhibitors

A novel thiazolopyrimidinone series of PI3K-beta selective inhibitors has been identified. This chemotype has provided an excellent tool compound, <b>18</b>, that showed potent growth inhibition in the PTEN-deficient breast cancer cell line MDA-MB-468 under anchorage-independent conditions, and it also demonstrated pharmacodynamic effects and efficacy in a PTEN-deficient prostate cancer PC-3 xenograft mouse model

Discovery of a Novel 2,6-Disubstituted Glucosamine Series of Potent and Selective Hexokinase 2 Inhibitors

A novel series of potent and selective hexokinase 2 (HK2) inhibitors, 2,6-disubstituted glucosamines, has been identified based on HTS hits, exemplified by compound <b>1</b>. Inhibitor-bound crystal structures revealed that the HK2 enzyme could adopt an “induced-fit” conformation. The SAR study led to the identification of potent HK2 inhibitors, such as compound <b>34</b> with greater than 100-fold selectivity over HK1. Compound <b>25</b> inhibits <i>in situ</i> glycolysis in a UM-UC-3 bladder tumor cell line via ¹³CNMR measurement of [3-¹³C]­lactate produced from [1,6-¹³C₂]­glucose added to the cell culture

Discovery of a Novel 2,6-Disubstituted Glucosamine Series of Potent and Selective Hexokinase 2 Inhibitors

A novel series of potent and selective hexokinase 2 (HK2) inhibitors, 2,6-disubstituted glucosamines, has been identified based on HTS hits, exemplified by compound <b>1</b>. Inhibitor-bound crystal structures revealed that the HK2 enzyme could adopt an “induced-fit” conformation. The SAR study led to the identification of potent HK2 inhibitors, such as compound <b>34</b> with greater than 100-fold selectivity over HK1. Compound <b>25</b> inhibits <i>in situ</i> glycolysis in a UM-UC-3 bladder tumor cell line via ¹³CNMR measurement of [3-¹³C]­lactate produced from [1,6-¹³C₂]­glucose added to the cell culture