Constitutively-active androgen receptor splice variants (AR-V) lacking the ligand-binding domain have been implicated in the pathogenesis of castration-resistant prostate cancer and in mediating resistance to newer drugs that target the androgen axis. AR-V regulate expression of both canonical AR targets and a unique set of cancer-specific targets that are enriched for cell cycle functions. However, little is known about how AR-V control gene expression. Here we report that two major AR-V, termed AR-V7 and ARv567es, not only homodimerize and heterodimerize with each other but also heterodimerize with full-length androgen receptor (AR-FL) in an androgen-independent manner. We found that heterodimerization of AR-V and AR-FL was mediated by N- and C-terminal interactions and by the DNA-binding domain of each molecule, whereas AR-V homodimerization was mediated only by DNA-binding domain interactions. Notably, AR-V dimerization was required to transactivate target genes and to confer castration-resistant cell growth. Our results clarify the mechanism by which AR-V mediate gene regulation and provide a pivotal pathway for rational drug design to disrupt AR-V signaling, as a rational strategy for effective treatment of advanced prostate cancer.

Hepatitis B virus (HBV) infection is a common infectious disease. Here we perform a genome-wide association study (GWAS) among Chinese populations to identify novel genetic loci involved in persistent HBV infection. GWAS scan is performed in 1,251 persistently HBV infected subjects (PIs, cases) and 1,057 spontaneously recovered subjects (SRs, controls), followed by replications in four independent populations totally consisting of 3,905 PIs and 3,356 SRs. We identify a novel locus at 8p21.3 (index rs7000921, odds ratio=0.78, P=3.2 × 10−12). Furthermore, we identify significant expression quantitative trait locus associations for INTS10 gene at 8p21.3. We demonstrate that INST10 suppresses HBV replication via IRF3 in liver cells. In clinical plasma samples, we confirm that INST10 levels are significantly decreased in PIs compared with SRs, and negatively correlated with the HBV load. These findings highlight a novel antiviral gene INTS10 at 8p21.3 in the clearance of HBV infection.

This paper develops a model predictive flocking control scheme for second-order multi-agent systems with input constraints. By penalizing both the control effort and the irregularity of the position distribution to a desired lattice formation, a decentralized controller is designed based only on neighboring measurements. Geometric properties of the optimal path are used to provide conditions guaranteeing convergence to a rigid -lattice flock avoiding inter-agent collision. Finally, numerical simulation is carried out to demonstrate the effectiveness of the proposed design.Index Terms-Flocking, model predictive control, multi-agent system.

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In recent ten years, wireless sensor network technology has a rapid development. After a brief introduction of the wireless sensor network, some main research results of energy conservation and node deployment is provided. Then the applications of WSN in the medical health, environment and agriculture, intelligent home furnishing and building, military, space and marine exploration are outlined. In addition, we analyze the advantage of WSN in these areas. Finally, we summarize the main factors that affect the applications of wireless sensor network.

A large-scale system consisting of self-propelled particles, moving under the directional alignment rule ͑DAR͒, can often self-organize to an ordered state that emerges from an initially rotationally symmetric configuration. It is commonly accepted that the DAR, which leads to effective long-range interactions, is the underlying mechanism contributing to the collective motion. However, in this paper, we demonstrate that a swarm under the DAR has unperceived and inherent singularities. Furthermore, we show that the compelled symmetry-breaking effects at or near the singularities, as well as the topological connectivity of the swarm in the evolution process, contribute fundamentally to the emergence of the collective behavior; and the elimination or weakening of singularities in the DAR will induce an unexpected sharp transition from coherent movement to isotropic dispersion. These results provide some insights into the fundamental issue of collective dynamics: What is the underlying mechanism causing the spontaneous symmetry breaking and leading to eventual coherent motion?

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