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All herpesviruses encode a conserved DNA polymerase that is required for viral genome replication and serves as an important therapeutic target. Currently available herpesvirus therapies include nucleoside and non-nucleoside inhibitors (NNI) that target the DNA-bound state of herpesvirus polymerase and block replication. Here we report the ternary complex crystal structure of Herpes Simplex Virus 1 DNA polymerase bound to DNA and a 4-oxo-dihydroquinoline NNI, PNU-183792 (PNU), at 3.5 Å resolution. PNU bound at the polymerase active site, displacing the template strand and inducing a conformational shift of the fingers domain into an open state. These results demonstrate that PNU inhibits replication by blocking association of dNTP and stalling the enzyme in a catalytically incompetent conformation, ultimately acting as a nucleotide competing inhibitor (NCI). Sequence conservation of the NCI binding pocket further explains broad-spectrum activity while a direct interaction between PNU and residue V823 rationalizes why mutations at this position result in loss of inhibition., Various herpesvirus therapeutics target the viral DNA polymerase. Here, the authors present the crystal structure of herpesvirus polymerase in the elongating state with bound primer-template DNA and the broad-spectrum non-nucleoside inhibitor PNU-183792, which is of interest for further drug design.

The purpose of the work in this paper is to gain insight into several fundamental questions that arise whenever a distributed multiple-vehicle control system is endowed with communication capabilities. These fundamental questions include: what data should each vehicle share?, how frequently should communication take place?, and what benefit does communication provide? These questions are evaluated with respect to a target tracking task in which multiple pursuit vehicles estimate the state of a target vehicle. This task has three main components: communication, estimation, and control. Communication takes place on a broadcast network, estimation is achieved with an Unscented Kalman Filters, and the controller is behavior-based. Simulation results show that communication always improves distributed estimate results. Which information to transmit depends on available bandwidth, and more frequent communication generally yields better estimates. Simulation results also show how coordinated control can be beneficial to target tracking in a cluttered environment.

A series of three new cyano-containing diamines based upon 1,4-bis(4-aminophenoxy)benzene was synthesized and polymerized with six different dianhydrides to yield 18 different polyimides. Due to the high dipole moment of the cyano group, it was believed that these polymers would display differing degrees of electroactivity depending upon the degree and position of cyano substitution. The type of dianhydride bridging group and length are also factors that affect the electroactivity of polyimides. Polyimides based upon 1,4-bis(4-aminophenoxy)benzene were used as reference materials by which the respective cyano-containing analogs were compared. As the degree of cyano group substitution increased, the glass transition temperature increased. As cyano substitution increased, the polymer chain flexibility decreased due to hindered rotation about the phenyl-ether-phenyl linkages in the diamine portion of the polymer. The tensile moduli ranged from 2.97 to 4.57 GPa and ultimate tensile strengths from 79 to 156 MPa, which are typical values of aromatic polyimides.

An improved, less expensive route to a high-performance poly(aryl ether phenylquinoxaline) has been developed. Thus, an isomeric mixture of self- polymerizable (A-B) quinoxaline monomers, 2-(4-hydroxyphenyl)-3-phenyl-6- chloroquinoxaline and 3-(4-hydroxyphenyl)-2-phenyl-6-chloroquinoxaline, was prepared by the condensation of 1,2-diamino-4-chlorobenzene with 4-hydroxybenzil The mixture was polymerized at 200°C in benzophenone containing potassium carbonate and a freshly prepared copper(I)chloride/quinoline catalyst mixture. The polymer obtained displayed an intrinsic viscosity of 1.53 dl/g (m-cresol at 30.0±0.1°C and a glass transition temperature of 252°C (DSC), similar to samples prepared previously from an analogous fluorine-substituted mixture.