Influence of viral genes on the cell-to-cell spread of RNA silencing

The turnip crinkle virus-based vector TCV–GFPDCP had been devised previously to study cell-to-cell and long-distance spread of virus-induced RNA silencing. TCV–GFPDCP, which had been constructed by replacing the coat protein (CP) gene with a green fluorescent protein (GFP) coding sequence, was able to induce RNA silencing in single epidermal cells, from which RNA silencing spread from cell-to-cell. Using this unique local silencing assay together with mutagenesis analysis, two TCV genes, p8 and p9, which were involved in the intercellular spread of virus-induced RNA silencing, were identified. TCV–GFPDCP and its p8- or p9-mutated derivatives, TCVmp8–GFPDCP and TCVmp9–GFPDCP, replicated efficiently but were restricted to single Nicotiana benthamiana epidermal cells. TCV–GFPDCP, TCVmp8–GFPDCP, or TCVmp9–GFPDCP was able to initiate RNA silencing that targeted and degraded recombinant viral RNAs in inoculated leaves of the GFP-expressing N. benthamiana line 16c. However, cell-to-cell spread of silencing to form silencing foci was triggered only by TCV–GFPDCP. Non-replicating TCVmp88–GFPDCP and TCVmp28mp88–GFPDCP with dysfunctional replicase genes, and single-stranded gfp RNA did not induce RNA silencing. Transient expression of the TCV p9 protein could effectively complement TCVmp9–GFPDCP to facilitate intercellular spread of silencing. These data suggest that the plant cellular trafficking machinery could hijack functional viral proteins to permit cell-to-cell movement of RNA silencing

Control energy of complex networks towards distinct mixture states

Controlling complex networked systems is a real-world puzzle that remains largely unsolved. Despite recent progress in understanding the structural characteristics of network control energy, target state and system dynamics have not been explored. We examine how varying the final state mixture affects the control energy of canonical and conformity-incorporated dynamical systems. We find that the control energy required to drive a network to an identical final state is lower than that required to arrive a non-identical final state. We also demonstrate that it is easier to achieve full control in a conformity-based dynamical network. Finally we determine the optimal control strategy in terms of the network hierarchical structure. Our work offers a realistic understanding of the control energy within the final state mixture and sheds light on controlling complex systems.This work was funded by The National Natural Science Foundation of China (Grant Nos. 61763013, 61703159, 61403421), The Natural Science Foundation of Jiangxi Province (No. 20171BAB212017), The Measurement and Control of Aircraft at Sea Laboratory (No. FOM2016OF010), and China Scholarship Council (201708360048). The Boston University Center for Polymer Studies is supported by NSF Grants PHY-1505000, CMMI-1125290, and CHE-1213217, and by DTRA Grant HDTRA1-14-1-0017. (61763013 - National Natural Science Foundation of China; 61703159 - National Natural Science Foundation of China; 61403421 - National Natural Science Foundation of China; 20171BAB212017 - Natural Science Foundation of Jiangxi Province; FOM2016OF010 - Measurement and Control of Aircraft at Sea Laboratory; 201708360048 - China Scholarship Council; PHY-1505000 - NSF; CMMI-1125290 - NSF; CHE-1213217 - NSF; HDTRA1-14-1-0017 - DTRA)Published versio

An agent-based modeling template for a cohort of veterans with diabetic retinopathy

BACKGROUNDAgent-based models are valuable for examining systems where large numbers of discrete individuals interact with each other, or with some environment. Diabetic Veterans seeking eye care at a Veterans Administration hospital represent one such cohort.OBJECTIVEThe objective of this study was to develop an agent-based template to be used as a model for a patient with diabetic retinopathy (DR). This template may be replicated arbitrarily many times in order to generate a large cohort which is representative of a real-world population, upon which in-silico experimentation may be conducted.METHODSAgent-based template development was performed in java-based computer simulation suite AnyLogic Professional 6.6. The model was informed by medical data abstracted from 535 patient records representing a retrospective cohort of current patients of the VA St. Louis Healthcare System Eye clinic. Logistic regression was performed to determine the predictors associated with advancing stages of DR. Predicted probabilities obtained from logistic regression were used to generate the stage of DR in the simulated cohort.RESULTSThe simulated cohort of DR patients exhibited no significant deviation from the test population of real-world patients in proportion of stage of DR, duration of diabetes mellitus (DM), or the other abstracted predictors. Simulated patients after 10 years were significantly more likely to exhibit proliferative DR (PCONCLUSIONSAgent-based modeling is an emerging platform, capable of simulating large cohorts of individuals based on manageable data abstraction efforts. The modeling method described may be useful in simulating many different conditions where course of disease is described in categorical stages

Characterization of a novel type of HIV-1 particle assembly inhibitor using a quantitative Luciferase-Vpr packaging-based assay

The HIV-1 auxiliary protein Vpr and Vpr-fusion proteins can be copackaged with Gag precursor (Pr55Gag) into virions or membrane-enveloped virus-like particles (VLP). Taking advantage of this property, we developed a simple and sensitive method to evaluate potential inhibitors of HIV-1 assembly in a living cell system. Two proteins were coexpressed in recombinant baculovirus-infected Sf9 cells, Pr55Gag, which formed the VLP backbone, and luciferase fused to the N-terminus of Vpr (LucVpr). VLP-encapsidated LucVpr retained the enzymatic activity of free luciferase. The levels of luciferase activity present in the pelletable fraction recovered from the culture medium correlated with the amounts of extracellular VLP released by Sf9 cells assayed by conventional immunological methods. Our luciferase-based assay was then applied to the characterization of betulinic acid (BA) derivatives that differed from the leader compound PA-457 (or DSB) by their substituant on carbon-28. The beta-alanine-conjugated and lysine-conjugated DSB could not be evaluated for their antiviral potentials due to their high cytotoxicity, whereas two other compounds with a lesser cytotoxicity, glycine-conjugated and ε-NH-Boc-lysine-conjugated DSB, exerted a dose-dependent negative effect on VLP assembly and budding. A fifth compound with a low cytotoxicity, EP-39 (ethylene diamine-conjugated DSB), showed a novel type of antiviral effect. EP-39 provoked an aberrant assembly of VLP, resulting in nonenveloped, morula-like particles of 100-nm in diameter. Each morula was composed of nanoparticle subunits of 20-nm in diameter, which possibly mimicked transient intermediates of the HIV-1 Gag assembly process. Chemical cross-linking in situ suggested that EP-39 favored the formation or/and persistence of Pr55Gag trimers over other oligomeric species. EP-39 showed a novel type of negative effect on HIV-1 assembly, targeting the Pr55Gag oligomerisation. The biological effect of EP-39 underlined the critical role of the nature of the side chain at position 28 of BA derivatives in their anti-HIV-1 activity

Imitative Follower Deception in Stackelberg Games

Information uncertainty is one of the major challenges facing applications of game theory. In the context of Stackelberg games, various approaches have been proposed to deal with the leader's incomplete knowledge about the follower's payoffs, typically by gathering information from the leader's interaction with the follower. Unfortunately, these approaches rely crucially on the assumption that the follower will not strategically exploit this information asymmetry, i.e., the follower behaves truthfully during the interaction according to their actual payoffs. As we show in this paper, the follower may have strong incentives to deceitfully imitate the behavior of a different follower type and, in doing this, benefit significantly from inducing the leader into choosing a highly suboptimal strategy. This raises a fundamental question: how to design a leader strategy in the presence of a deceitful follower? To answer this question, we put forward a basic model of Stackelberg games with (imitative) follower deception and show that the leader is indeed able to reduce the loss due to follower deception with carefully designed policies. We then provide a systematic study of the problem of computing the optimal leader policy and draw a relatively complete picture of the complexity landscape; essentially matching positive and negative complexity results are provided for natural variants of the model. Our intractability results are in sharp contrast to the situation with no deception, where the leader's optimal strategy can be computed in polynomial time, and thus illustrate the intrinsic difficulty of handling follower deception. Through simulations we also examine the benefit of considering follower deception in randomly generated games

Fabrication and I-V Characterization of ZnO Nanorod Based Metal-Insulator-Semiconductor Junction

We report on the characteristics of a ZnO based metal insulator semiconductor (MIS) diode comprised of a heterostructure of n-ZnO nanorods/n-GaN. The MIS structure consisted of unintentional - doped n type ZnO nanorods grown on n-GaN sample using hydrothermal synthesis at low temperature (100°). The ZnO nanorod layer was vertically grown from the GaN sample, having the diameter 100nm and length 2µm. Then, an insulator layer for electrical isolation was deposited on the top of ZnO nanorod layer by using spin coating method. A metal layer (gold) was finally deposited on the top. The I-V dependences show a rectifying diode like behavior with a leakage current of 2.10⁻⁵ A and a threshold voltage of about 3V. Depend on the thickness of the insulator, the I-V dependences of the n-ZnO/n-GaN heterostructure was varied from rectifying behavior to Ohmic and nearly linear.Singapore-MIT Alliance (SMA

ZnO Nanorods Grown on p-GaN Using Hydrothermal Synthesis and Its Optoelectronic Devices Application

The ZnO nanorods with the length of 1-1.5 μm were deposited on p-GaN by hydrothermal synthesis at low temperature 100°C. The structural and optical properties of the as-grown ZnO rods were investigated by X-Ray diffraction (XRD) and photoluminescence (PL) spectra. After annealing treatment the as-grown films in air at 600°C, 30min, and the ZnO rods showed good crystallinity and optical properties with strong UV emission at 378 nm. In addition, a sharp UV emission peak at 369.45 nm with the FWHM 20 meV, which attributed to the bound exciton recombination, was also observed from the ZnO rods at 80K. Next, the e-beam evaporation method was used to deposit metal contact on n-ZnO and p-GaN. Here, we use Au and Ni/Au as metal contacts for n-ZnO and p-GaN, respectively. The current-voltage characteristics of the fabricated n-ZnO/p-GaN heterojunction revealed rectifying behavior with a leakage current of 10⁻⁸ A at -10V, a forward current 4x10⁻⁶ A at 10V bias. The heterojunction also showed a good photoresponse, with the change of the current – voltage characteristics under ultraviolet illumination. Under UV illumination, the forward turn on voltage changed to 7.5V. This result showed the ability to manipulate the electron transport in the ZnO based heterojunction devices.Singapore-MIT Alliance (SMA

An improved game-theoretic approach to uncover overlapping communities

How can we uncover overlapping communities from complex networks to understand the inherent structures and functions? Chen et al. firstly proposed a community game (Game) to study this problem, and the overlapping communities have been discovered when the game is convergent. It is based on the assumption that each vertex of the underlying network is a rational game player to maximize its utility. In this paper, we investigate how similar vertices affect the formation of community game. The Adamic–Adar Index (AA Index) has been employed to define the new utility function. This novel method has been evaluated on both synthetic and real-world networks. Experimental study shows that it has significant improvement of accuracy (from 4.8% to 37.6%) compared with the Game on 10 real networks. It is more efficient on Facebook networks (FN) and Amazon co-purchasing networks than on other networks. This result implicates that “friend circles of friends” of Facebook are valuable to understand the overlapping community division

Charge storage in nanocrystal systems: Role of defects?

Wet thermal oxidations of polycrystalline Si₀.₅₄Ge₀.₄₆ films at 600°C for 30 and 50 min were carried out. A stable mixed oxide was obtained for films that were oxidized for 50 min. For film oxidized for 30 min, however, a mixed oxide with Ge nanocrystallites embedded in the oxide matrix was obtained. A trilayer gate stack structure that consisted of tunnel oxide/oxidized polycrystalline Si₀.₅₄Ge₀.₄₆/rf sputtered SiO₂ layers was fabricated. We found that with a 30 min oxidized middle layer, annealing the structure in N₂ ambient results in the formation of germanium nanocrystals and the annealed structure exhibits memory effect. For a trilayer structure with middle layer oxidized for 50 min, annealing in N₂ showed no nanocrystal formation and also no memory effect. Annealing the structures with 30 or 50 min oxidized middle layer in forming gas ambient resulted in nanocrystals embedded in the oxide matrix but no memory effect. This suggests that the charge storage mechanism for the trilayer structure is closely related to the interfacial traps of the nanocrystals.Singapore-MIT Alliance (SMA