The complement system in age-related macular degeneration

Age-related macular degeneration (AMD) is a chronic and progressive degenerative disease of the retina, which culminates in blindness and affects mainly the elderly population. AMD pathogenesis and pathophysiology are incredibly complex due to the structural and cellular complexity of the retina, and the variety of risk factors and molecular mechanisms that contribute to disease onset and progression. AMD is driven by a combination of genetic predisposition, natural ageing changes and lifestyle factors, such as smoking or nutritional intake. The mechanism by which these risk factors interact and converge towards AMD are not fully understood and therefore drug discovery is challenging, where no therapeutic attempt has been fully effective thus far. Genetic and molecular studies have identified the complement system as an important player in AMD. Indeed, many of the genetic risk variants cluster in genes of the alternative pathway of the complement system and complement activation products are elevated in AMD patients. Nevertheless, attempts in treating AMD via complement regulators have not yet been successful, suggesting a level of complexity that could not be predicted only from a genetic point of view. In this review, we will explore the role of complement system in AMD development and in the main molecular and cellular features of AMD, including complement activation itself, inflammation, ECM stability, energy metabolism and oxidative stress.

     

The futility of decision making research

We have each spent more than 50 years doing research that has had little impact. Even more lamentable is that our field, judgment and decision making (JDM), has on the whole had little impact during that span. We attribute that failure to the use of methodologies that emphasize testing models rather than looking for differences in behavior. The “cognitive revolution” led the field astray, toward the goal of studying model fit rather than comparing observable results. With modeling as the goal, experimentation was stultified. Simple tasks became dominant. Although a poor metaphor for real decision making, the gambling paradigm has lasted forever because the inputs to the decision are known to the researcher and thus easily modeled.     

免疫缺陷大鼠模型的研究进展

免疫缺陷动物模型是指通过筛选自发突变或者基因工程改造建立的缺失一种或多种免疫系统组分，并用于生物医学研究的动物模型。免疫缺陷小鼠模型发展较为成熟，为人源化、患者来源异种移植(patient-derived xenograft, PDX)、干细胞移植以及传染性疾病等研究提供了良好的工具。与小鼠相比，大鼠具有体型更大，代谢和生理与人更接近，更易进行手术操作、样本获取，以及长期应用于临床前毒理和药理的评估等优势。因此，近年来出现了各种免疫缺陷大鼠模型。文章通过动物模型之间的比较，着重综述了免疫缺陷大鼠模型的最新进展，并展望其在干细胞研究和抗肿瘤治疗中的应用前景。     

融媒体背景下传统民营科技型企业的互联网转型:协同进化视角

借助隐喻手段,基于融媒体发展背景,以协同进化为理论依据,剖析传统民营科技型企业的互联网转型过程,总结机理与路径,提出协同进化式转型的理论模型.以千城智联(上海)网络科技有限公司为案例企业,分析其与地方电视台的协同进化过程,研究发现:①基因改变意味着组织认知模式的变化,具体表现是互联网思维的建立以及从单式思维到链式思维的转变;②协同进化基本路径为企业基因改变→企业行为转变→合作方基因改变→合作方行为转变→企业与合作方性状变化;③协同进化的标志是生态位改变,后者由协同关系的转变来衡量,分别经历了买卖关系、资源共享关系、价值共创与共享关系三种状态;④协同关系的演进激发平台网络效应的形成.     

Robust Chattering-Free Finite Time Attitude Tracking Control with Input Saturation

This paper addresses the attitude tracking control problem of a rigid spacecraft in the presence of the modeling uncertainty, external disturbance, and saturated control input by designing two robust attitude tracking controllers. The basic controller is formulated using an integral sliding mode surface which is continuous and provides an asymptotic convergence rate for the closed-loop system. In this case, only the external disturbance with the prior information is considered. Then, to provide a finite time convergence rate and further improve the robustness of the control system under the unknown system uncertainty containing both the modeling uncertainty and external disturbance,a novel integral terminal sliding mode surface(ITSMS) is designed and associated with the continuous adaptive control method. Besides, a command filter is utilized to deal with the immeasurability problem within the proposed ITSMS and an auxiliary system to counteract the input saturation problem. Digital simulations are presented to verify the effectiveness of the proposed controllers.     

Bidirectional Feedback Dynamic Particle Filter with Big Data for the Particle Degeneracy Problem

Particle Filter(PF) is a data assimilation method to solve recursive state estimation problem which does not depend on the assumption of Gaussian noise, and is able to be applied for various systems even with non-linear and non-Gaussian noise. However, while applying PF in dynamic systems, PF undergoes particle degeneracy,sample impoverishment, and problems of high computational complexity. Rapidly developing sensing technologies are providing highly convenient availability of real-time big traffic data from the system under study like never before. Moreover, some sensors can even receive control commands to adjust their monitoring parameters. To address these problems, a bidirectional dynamic data-driven improvement framework for PF(B3 DPF) is proposed.The B3 DPF enhances feedback between the simulation model and the big traffic data collected by the sensors,which means the execution strategies(sensor data management, parameters used in the weight computation,resampling) of B3 DPF can be optimized based on the simulation results and the types and dimensions of traffic data injected into B3 DPF can be adjusted dynamically. The first experiment indicates that the B3 DPF overcomes particle degeneracy and sample impoverishment problems and accurately estimates the state at a faster speed than the normal PF. More importantly, the new method has higher accuracy for multidimensional random systems.In the rest of experiments, the proposed framework is applied to estimate the traffic state on a real road network and obtains satisfactory results. More experiments can be designed to validate the universal properties of B3 DPF.     

Structure and function of Zika virus NS5 protein: perspectives for drug design

Zika virus (ZIKV) belongs to the positive-sense single-stranded RNA-containing Flaviviridae family. Its recent outbreak and association with human diseases (e.g. neurological disorders) have raised global health concerns, and an urgency to develop a therapeutic strategy against ZIKV infection. However, there is no currently approved antiviral against ZIKV. Here we present a comprehensive overview on recent progress in structure–function investigation of ZIKV NS5 protein, the largest non-structural protein of ZIKV, which is responsible for replication of the viral genome, RNA capping and suppression of host interferon responses. Structural comparison of the N-terminal methyltransferase domain and C-terminal RNA-dependent RNA polymerase domain of ZIKV NS5 with their counterparts from related viruses provides mechanistic insights into ZIKV NS5-mediated RNA replication, and identifies residues critical for its enzymatic activities. Finally, a collection of recently identified small molecule inhibitors against ZIKV NS5 or its closely related flavivirus homologues are also discussed.