GuanHua Chen

Identification of influenza A nucleoprotein as an antiviral target

Influenza A remains a significant public health challenge because of the emergence of antigenically shifted or highly virulent strains. Antiviral resistance to available drugs such as adamantanes or neuraminidase inhibitors has appeared rapidly, creating a need for new antiviral targets and new drugs for influenza virus infections. Using forward chemical genetics, we have identified influenza A nucleoprotein (NP) as a druggable target and found a small-molecule compound, nucleozin, that triggers the aggregation of NP and inhibits its nuclear accumulation. Nucleozin impeded influenza A virus replication in vitro with a nanomolar median effective concentration (EC50) and protected mice challenged with lethal doses of avian influenza A H5N1. Our results demonstrate that viral NP is a valid target for the development of small-molecule therapies.

Sequential Establishment of Stripe Patterns in an Expanding Cell Population

A synthetic circuit implementing density-controlled bacterial motility autonomously produces a tunable stripe pattern. Periodic stripe patterns are ubiquitous in living organisms, yet the underlying developmental processes are complex and difficult to disentangle. We describe a synthetic genetic circuit that couples cell density and motility. This system enabled programmed Escherichia coli cells to form periodic stripes of high and low cell densities sequentially and autonomously. Theoretical and experimental analyses reveal that the spatial structure arises from a recurrent aggregation process at the front of the continuously expanding cell population. The number of stripes formed could be tuned by modulating the basal expression of a single gene. The results establish motility control as a simple route to establishing recurrent structures without requiring an extrinsic pacemaker.

Identification of novel small-molecule inhibitors of severe acute respiratory syndrome-associated coronavirus by chemical genetics.

Abstract The severe acute respiratory syndrome-associated coronavirus (SARS-CoV) infected more than 8,000 people across 29 countries and caused more than 900 fatalities. Based on the concept of chemical genetics, we screened 50,240 structurally diverse small molecules from which we identified 104 compounds with anti-SARS-CoV activity. Of these 104 compounds, 2 target the SARS-CoV main protease (Mpro), 7 target helicase (Hel), and 18 target spike (S) protein-angiotensin-converting enzyme 2 (ACE2)-mediated viral entry. The EC50 of the majority of the 104 compounds determined by SARS-CoV plaque reduction assay were found to be at low micromolar range. Three selected compounds, MP576, HE602, and VE607, validated to be inhibitors of SARS-CoV Mpro, Hel, and viral entry, respectively, exhibited potent antiviral activity (EC50 < 10 μM) and comparable inhibitory activities in target-specific in vitro assays.

Time-dependent Density Functional Theory For Open Systems

With our proof of the holographic electron density theorem for time-dependent systems, a first-principles method for any open electronic system is established. By introducing the self-energy density functionals for the dissipative interactions between the reduced system and its environment, we develop a time-dependent densityfunctional theory formalism based on an equation of motion for the Kohn-Sham reduced single-electron density matrix of the reduced system. Two approximate schemes are proposed for the dissipative interactions, the complete second-order approximation and the wide-band limit approximation. A numerical method based on the wide-band limit approximation is subsequently developed and implemented to simulate the steady and transient current through various realistic molecular devices. Simulation results are presented and discussed.

A novel polyphase multipole square-wave permanent magnet motor drive for electric vehicles

A novel high-power-density permanent magnet (PM) motor drive for electric vehicles (EVs) is proposed. The motor is a polyphase multipole square-wave PM motor, which can be classified as a kind of PM brushless DC motor. The distinct features of the proposed motor as compared to those of the conventional PM brushless DC motor are as follows. First, the multipole magnetic circuit arrangement enables the minimization of the magnetic yoke, resulting in the reduction of motor volume and weight. Second, the coil span is purposely designed to be equal to one slot pitch, thus saving the amount of copper used. Third, by using a fractional number of slots per pole per phase, the arrangement of the numbers of poles and slots is so unique that the magnetic force between the stator and the rotor at any rotating position is uniform, hence eliminating the cogging torque that usually occurs in PM motors. Finally, the motor can be controlled to operate at a constant torque region and a constant power region with field weakening, thus both high starting torque and high cruising speed can be achieved. Therefore, as the proposed motor drive possesses the distinct advantages of high power density, high efficiency, and superior dynamic performance, it is very suitable for EV applications. A prototype of a five-phase 22-pole 5 kW motor drive has been designed for an experimental EV. >

Elementary building blocks of graphene-nanoribbon-based electronic devices

Graphene nanoribbon junction based electronic devices are proposed in this letter. Nonequilibrium Green’s function calculations show that nanoribbon junctions tailored from single layer graphene with different edge shapes and widths can act as metal/semiconductor junctions and quantum dots can be implemented. In virtue of the possibilities of patterning monolayer graphene down to atomic precision, these structures, quite different from the previously reported two-dimensional bulk graphene or carbon nanotube devices, are expected to be used as the building blocks of the future nanoelectronics.Graphene nano-ribbons junctions based electronic devices are proposed in this Letter. Non-equilibrium Green function calculations show that nano-ribbon junctions tailored from single layer graphene with different edge shape and width can act as metal-semiconductor junctions and quantum dots can be implemented. In virtue of the possibilities of patterning monolayer graphene down to atomic precision, these structures, quite different from the previously reported two-dimensional bulk graphene or carbon nanotube devices, are expected to be used as the building blocks of the future nano-electronics.

Combined first-principles calculation and neural-network correction approach for heat of formation

Despite their success, the results of first-principles quantum mechanical calculations contain inherent numerical errors caused by various intrinsic approximations. We propose here a neural-network-based algorithm to greatly reduce these inherent errors. As a demonstration, this combined quantum mechanical calculation and neural-network correction approach is applied to the evaluation of standard heat of formation ΔfH⊖ for 180 small- to medium-sized organic molecules at 298 K. A dramatic reduction of numerical errors is clearly shown with systematic deviation being eliminated. For example, the root-mean-square deviation of the calculated ΔfH⊖ for the 180 molecules is reduced from 21.4 to 3.1 kcal mol−1 for B3LYP/6-311+G(d,p) and from 12.0 to 3.3 kcal mol−1 for B3LYP/6-311+G(3df,2p) before and after the neural-network correction.

A tribological study of double-walled and triple-walled carbon nanotube oscillators

We reported in a previous study (Zhao et al 2003 Phys. Rev. Lett. 91 175504) that energy transfer from the orderly intertube translational oscillation to intratube vibrational modes for an isolated system of two coaxial carbon nanotubes at low temperatures takes place primarily via two distinct types of collective motion of the carbon nanotubes, i.e., off-axial rocking motion of the inner tube and radial wavy motion of the outer tube, and that these types of motion may or may not occur for such a system, depending upon the amount of the initial extrusion of the inner tube out of the outer tube. Our present study, using micro-canonical molecular dynamics (MD), indicates the existence of an energy threshold, largely independent of system sizes and configurations, for a double-walled nano-oscillator to deviate from the intertube translational oscillation and thus to encounter significant intertube friction. The frictional forces associated with several distinct dissipative mechanisms are all found to exhibit no proportional dependence upon the normal force between the two surfaces in relative sliding, contrary to the conventional understanding resulting from tribological studies of macroscopic systems. Furthermore, simulation has been performed at different initial temperatures, revealing a strong temperature dependence of friction in the early phase of oscillation. Finally, our studies of three-walled nano-oscillators show that an initial extrusion of the middle tube can cause inner-tube off-axial instabilities, leading to strong frictional effects.

Electronic Coherence and Nonlinear Susceptibilities of Conjugated Polyenes

A dynamic theory that connects electronic motions and the nonlinear optical response of conjugated polyenes is developed by introducing the concept of electronic normal modes. A useful picture for the mechanism of optical nonlinearities is obtained by identifying the few dominant modes. This quasi-particle electron-hole representation establishes a close analogy with small semiconductor particles (quantum dots) and is very different from the traditional approach based on electronic eigenstates. The effective conjugation length (coherence size), which controls the scaling and saturation of the static third-order susceptibility X(3) with the number of double bonds, is related to the coherence of the relative motion of electron-hole pairs created upon optical excitation.

Valence‐bond charge‐transfer solvation model for nonlinear optical properties of organic molecules in polar solvents

A simple model is developed for predicting solvation effects on the nonlinear optical properties of charge transfer organic materials such as 1,1 dicyano,6‐(di‐butyl amine) hexatriene. This model is based on the valence‐bond charge‐transfer (VB‐CT) framework, using a continuum description of the solvent. The resulting VB‐CT solvation model leads to analytic formulas for the absorption frequency (Eg), the polarizability (α), the hyperpolarizabilities (β,γ,δ), and the bond length alternation with only one solvent dependent parameter (e, the dielectric constant of the solution). The theory involves just four solvent‐independent parameters, V0, t, SF, and Q which are related to the band gap, bandwidth, geometry, and dipole moment of the CT molecule [plus a length (RDA) and force constant (k) derivable from standard force fields]. The results are in good agreement with experiment.