lncRNA-dependent mechanisms of androgen-receptor-regulated gene activation programs.

Although recent studies have indicated roles of long non-coding RNAs (lncRNAs) in physiological aspects of cell-type determination and tissue homeostasis, their potential involvement in regulated gene transcription programs remains rather poorly understood. The androgen receptor regulates a large repertoire of genes central to the identity and behaviour of prostate cancer cells, and functions in a ligand-independent fashion in many prostate cancers when they become hormone refractory after initial androgen deprivation therapy. Here we report that two lncRNAs highly overexpressed in aggressive prostate cancer, PRNCR1 (also known as PCAT8) and PCGEM1, bind successively to the androgen receptor and strongly enhance both ligand-dependent and ligand-independent androgen-receptor-mediated gene activation programs and proliferation in prostate cancer cells. Binding of PRNCR1 to the carboxy-terminally acetylated androgen receptor on enhancers and its association with DOT1L appear to be required for recruitment of the second lncRNA, PCGEM1, to the androgen receptor amino terminus that is methylated by DOT1L. Unexpectedly, recognition of specific protein marks by PCGEM1-recruited pygopus 2 PHD domain enhances selective looping of androgen-receptor-bound enhancers to target gene promoters in these cells. In 'resistant' prostate cancer cells, these overexpressed lncRNAs can interact with, and are required for, the robust activation of both truncated and full-length androgen receptor, causing ligand-independent activation of the androgen receptor transcriptional program and cell proliferation. Conditionally expressed short hairpin RNA targeting these lncRNAs in castration-resistant prostate cancer cell lines strongly suppressed tumour xenograft growth in vivo. Together, these results indicate that these overexpressed lncRNAs can potentially serve as a required component of castration-resistance in prostatic tumours

Karriere-Handbuch

We design and synthesize four fused-ring electron acceptors based on 6,6,12,12-tetrakis(4-hexylphenyl)- indacenobis(dithieno[3,2-b;2′,3′-d]thiophene) as the electron- rich unit and 1,1-dicyanomethylene-3-indanones with 0− 2 fluorine substituents as the electron-deficient units. These four molecules exhibit broad (550−850 nm) and strong absorption with high extinction coefficients of (2.1−2.5) × 105 M−1 cm−1. Fluorine substitution downshifts the LUMO energy level, red-shifts the absorption spectrum, and enhances electron mobility. The polymer solar cells based on the fluorinated electron acceptors exhibit power conversion efficiencies as high as 11.5%, much higher than that of their nonfluorinated counterpart (7.7%). We investigate the effects of the fluorine atom number and position on electronic properties, charge transport, film morphology, and photovoltaic properties

Single-Junction Binary-Blend Nonfullerene Polymer Solar Cells with 12.1% Efficiency

A new fluorinated nonfullerene acceptor, ITIC-Th1, has been designed and synthesized by introducing fluorine (F) atoms onto the end-capping group 1,1-dicyanomethylene-3-indanone (IC). On the one hand, incorporation of F would improve intramolecular interaction, enhance the push–pull effect between the donor unit indacenodithieno[3,2-b]thiophene and the acceptor unit IC due to electron-withdrawing effect of F, and finally adjust energy levels and reduce bandgap, which is beneficial to light harvesting and enhancing short-circuit current density (JSC). On the other hand, incorporation of F would improve intermolecular interactions through C-F···S, C-F···H, and C-F···π noncovalent interactions and enhance electron mobility, which is beneficial to enhancing JSC and fill factor. Indeed, the results show that fluorinated ITIC-Th1 exhibits redshifted absorption, smaller optical bandgap, and higher electron mobility than the nonfluorinated ITIC-Th. Furthermore, nonfullerene organic solar cells (OSCs) based on fluorinated ITIC-Th1 electron acceptor and a wide-bandgap polymer donor FTAZ based on benzodithiophene and benzotriazole exhibit power conversion efficiency (PCE) as high as 12.1%, significantly higher than that of nonfluorinated ITIC-Th (8.88%). The PCE of 12.1% is the highest in fullerene and nonfullerene-based single-junction binary-blend OSCs. Moreover, the OSCs based on FTAZ:ITIC-Th1 show much better efficiency and better stability than the control devices based on FTAZ:PC71BM (PCE = 5.22%)

Dynamics Analysis and Optimal Control for a Delayed Rumor-Spreading Model

In this work, we analyze a delayed rumor-propagation model. First, we analyze the existence and boundedness of the solution of the model. Then, we give the conditions for the existence of the rumor-endemic equilibrium. Regrading the delay as a bifurcating parameter, we explore the local asymptotic stability and Hopf bifurcation of the rumor-endemic equilibrium. By a Lyapunov functional technique, we examine the global asymptotically stability of the rumor-free and the rumor-endemic equilibria. We provide two control variables in the rumor-spreading model with time delay, and get the optimal solution via the optimal procedures. Finally, we present some numerical simulations to verify our theoretical predictions. They illustrate that the delay is a crucial issue for system, and it can lead to not just Hopf bifurcation but also chaos

Dynamics Analysis of a Mathematical Model for New Product Innovation Diffusion

In this paper, a mathematical model with time-delay-related parameters and media coverage to describe the diffusion process of new products is proposed, in which the time-delay-related parameters denote the stage in which potential customers decide whether to adopt a new product. Then, the stability and the Hopf bifurcation of the proposed model are analyzed in detail. The center manifold theorem and the normal form theory are used to investigate the stability of the bifurcating periodic solution. Moreover, a numerical simulation is conducted to investigate the difference between the model with delay-dependent parameters and that with delay-independent parameters. The results show that there is significant difference between the two models

Dynamics Analysis and Optimal Control for a Delayed Rumor-Spreading Model

In this work, we analyze a delayed rumor-propagation model. First, we analyze the existence and boundedness of the solution of the model. Then, we give the conditions for the existence of the rumor-endemic equilibrium. Regrading the delay as a bifurcating parameter, we explore the local asymptotic stability and Hopf bifurcation of the rumor-endemic equilibrium. By a Lyapunov functional technique, we examine the global asymptotically stability of the rumor-free and the rumor-endemic equilibria. We provide two control variables in the rumor-spreading model with time delay, and get the optimal solution via the optimal procedures. Finally, we present some numerical simulations to verify our theoretical predictions. They illustrate that the delay is a crucial issue for system, and it can lead to not just Hopf bifurcation but also chaos

Gas concentration prediction model for fully mechanized coal mining face

In view of problems of gas concentration prediction method based on least squares support vector machine (LS-SVM) such as easy to fall into local optimal solution, low search efficiency and easy to occur premature convergence during parameter optimization process, a gas concentration prediction model based on ACO-LS-SVM was proposed. Firstly, k-means clustering analysis is performed on collected large amount of gas data on fully mechanized coal mining face to reduce dimension. Then, improved ant colony algorithm is used to optimize penalty parameters and kernel function parameters of LS-SVM, and the optimized parameters are substituted into the LS-SVM model for regression prediction. The simulation results show that when absolute error threshold of gas concentration is 0.03%, 0.04%, 0.05%, the prediction accuracy of the gas concentration prediction model based on ACO-LS-SVM is about 95%, which is better than SVM model and LS-SVM model