Risk Factors of Depression Screened by Two-Sample Mendelian Randomization Analysis:A Systematic Review

Objective This study explored the potentially modifiable factors for depression and major depressive disorder(MDD)from the MR-Base database and further evaluated the associations between drug targets with MDD.Methods We analyzed two-sample of Mendelian randomization(2SMR)using genetic variant depression(n=113,154)and MDD(n=208,811)from Genome-Wide Association Studies(GWAS).Separate calculations were performed with modifiable risk factors from MR-Base for 1,001 genomes.The MR analysis was performed by screening drug targets with MDD in the DrugBank database to explore the therapeutic targets for MDD.Inverse variance weighted(IVW),fixed-effect inverse variance weighted(FE-IVW),MR-Egger,weighted median,and weighted mode were used for complementary calculation.Results The potential causal relationship between modifiable risk factors and depression contained 459 results for depression and 424 for MDD.Also,the associations between drug targets and MDD showed that SLC6A4,GRIN2A,GRIN2C,SCN10A,and IL1B expression are associated with an increased risk of depression.In contrast,ADRB1,CHRNA3,HTR3A,GSTP1,and GABRG2 genes are candidate protective factors against depression.Conclusion This study identified the risk factors causally associated with depression and MDD,and estimated 10 drug targets with significant impact on MDD,providing essential information for formulating strategies to prevent and treat depression.

Integrated causal inference modeling uncovers novel causal factors and potential therapeutic targets of Qingjin Yiqi granules for chronic fatigue syndrome

Objective:Chronic fatigue syndrome(CFS)is a prevalent symptom of post-coronavirus disease 2019(COVID-19)and is associated with unclear disease mechanisms.The herbal medicine Qingjin Yiqi granules(QJYQ)constitute a clinically approved formula for treating post-COVID-19;however,its potential as a drug target for treating CFS remains largely unknown.This study aimed to identify novel causal factors for CFS and elucidate the potential targets and pharmacological mechanisms of action of QJYQ in treating CFS.Methods:This prospective cohort analysis included 4,212 adults aged≥65 years who were followed up for 7 years with 435 incident CFS cases.Causal modeling and multivariate logistic regression analysis were performed to identify the potential causal determinants of CFS.A proteome-wide,two-sample Mendelian randomization(MR)analysis was employed to explore the proteins associated with the identified causal factors of CFS,which may serve as potential drug targets.Furthermore,we performed a virtual screening analysis to assess the binding affinity between the bioactive compounds in QJYQ and CFS-associated proteins.Results:Among 4,212 participants(47.5%men)with a median age of 69 years(interquartile range:69–70 years)enrolled in 2004,435 developed CFS by 2011.Causal graph analysis with multivariate logistic regression identified frequent cough(odds ratio:1.74,95%confidence interval[CI]:1.15–2.63)and insomnia(odds ratio:2.59,95%CI:1.77–3.79)as novel causal factors of CFS.Proteome-wide MR analysis revealed that the upregulation of endothelial cell-selective adhesion molecule(ESAM)was causally linked to both chronic cough(odds ratio:1.019,95%CI:1.012–1.026,P=2.75 e^(−05))and insomnia(odds ratio:1.015,95%CI:1.008–1.022,P=4.40 e^(−08))in CFS.The major bioactive compounds of QJYQ,ginsenoside Rb2(docking score:−6.03)and RG4(docking score:−6.15),bound to ESAM with high affinity based on virtual screening.Conclusions:Our integrated analytical framework combining epidemiological,genetic,and in silico data provides a novel strategy for elucidating complex disease mechanisms,such as CFS,and informing models of action of traditional Chinese medicines,such as QJYQ.Further validation in animal models is warranted to confirm the potential pharmacological effects of QJYQ on ESAM and as a treatment for CFS.

Moving target defense of routing randomization with deep reinforcement learning against eavesdropping attack

Eavesdropping attacks have become one of the most common attacks on networks because of their easy implementation. Eavesdropping attacks not only lead to transmission data leakage but also develop into other more harmful attacks. Routing randomization is a relevant research direction for moving target defense, which has been proven to be an effective method to resist eavesdropping attacks. To counter eavesdropping attacks, in this study, we analyzed the existing routing randomization methods and found that their security and usability need to be further improved. According to the characteristics of eavesdropping attacks, which are “latent and transferable”, a routing randomization defense method based on deep reinforcement learning is proposed. The proposed method realizes routing randomization on packet-level granularity using programmable switches. To improve the security and quality of service of legitimate services in networks, we use the deep deterministic policy gradient to generate random routing schemes with support from powerful network state awareness. In-band network telemetry provides real-time, accurate, and comprehensive network state awareness for the proposed method. Various experiments show that compared with other typical routing randomization defense methods, the proposed method has obvious advantages in security and usability against eavesdropping attacks.

Passive target tracking with intermittent measurement based on random finite set

In the tracking problem for the maritime radiation source by a passive sensor,there are three main difficulties,i.e.,the poor observability of the radiation source,the detection uncertainty(false and missed detections)and the uncertainty of the target appearing/disappearing in the field of view.These difficulties can make the establishment or maintenance of the radiation source target track invalid.By incorporating the elevation information of the passive sensor into the automatic bearings-only tracking(BOT)and consolidating these uncertainties under the framework of random finite set(RFS),a novel approach for tracking maritime radiation source target with intermittent measurement was proposed.Under the RFS framework,the target state was represented as a set that can take on either an empty set or a singleton; meanwhile,the measurement uncertainty was modeled as a Bernoulli random finite set.Moreover,the elevation information of the sensor platform was introduced to ensure observability of passive measurements and obtain the unique target localization.Simulation experiments verify the validity of the proposed approach for tracking maritime radiation source and demonstrate the superiority of the proposed approach in comparison with the traditional integrated probabilistic data association(IPDA)method.The tracking performance under different conditions,particularly involving different existence probabilities and different appearance durations of the target,indicates that the method to solve our problem is robust and effective.

Numerical optimisation of a classical stochastic system for targeted energy transfer

The paper studies stochastic dynamics of a two-degree-of-freedom system,where a primary linear system is connected to a nonlinear energy sink with cubic stiffness nonlinearity and viscous damping.While the primary mass is subjected to a zero-mean Gaussian white noise excitation,the main objective of this study is to maximise the efficiency of the targeted energy transfer in the system.A surrogate optimisation algorithm is proposed for this purpose and adopted for the stochastic framework.The optimisations are conducted separately for the nonlinear stiffness coefficient alone as well as for both the nonlinear stiffness and damping coefficients together.Three different optimisation cost functions,based on either energy of the system’s components or the dissipated energy,are considered.The results demonstrate some clear trends in values of the nonlinear energy sink coefficients and show the effect of different cost functions on the optimal values of the nonlinear system’s coefficients.

大气湍流下部分相干涡旋光束经粗糙目标回波特性

利用广义Huygens-Fresnel原理和随机高斯粗糙面模型,研究部分相干高斯-谢尔模型涡旋光束的回波特性,通过特殊积分推导出部分相干涡旋光束经随机粗糙面散射后到达接收端的交叉谱密度函数和光强解析式,并进行仿真分析。结果表明:随着拓扑荷数、束腰半径和相干长度的增加,光强自相关函数曲线下降的越来越陡峭;在强湍流环境下,自相关函数衰减越来越严重;内尺度会影响光强自相关函数,并且随着内尺度的增大而衰减严重,外尺度对其影响作用不大;随着粗糙目标相干长度的增大,光强自相关函数的半峰宽值逐渐趋增大。

基于随机超曲面模型的机动星凸形扩展目标跟踪

针对具有强机动性的扩展目标跟踪问题,不仅需要估计目标的运动状态,还要准确识别目标机动过程中的形状变化。由于目标机动和模型的复杂所导致的高维非线性问题,提出了一种基于随机超曲面模型的扩展目标方向自适应跟踪算法。通过使用输入估计检测器对目标机动进行判断,再利用目标机动的大小修正形状参数的先验,其次基于先验信息更新量测,并结合无迹卡尔曼滤波算法,实现对机动扩展目标的状态跟踪和形状识别。利用均方根误差和quasi-Jaccard距离分别对目标质心位置的跟踪质量和形状的跟踪性能进行评价。仿真实验结果证明了该算法的有效性。

基于改进RRT的机器人路径规划算法

随机采样的RRT算法在非完整约束的规划问题中被广泛使用,但RRT方法存在收敛速度慢、随机性强、存在大量的冗余节点的问题,同时难以快速找到路径。针对以上问题提出一种改进的RRT算法。在提出一步记忆机制的基础上,算法基于历史拓展结果进行随机拓展或者向目标拓展;同时,将随机树拓展过程中因碰撞而拓展失败的节点进行随机旋转处理,以使随机树能够成功拓展;最后,采用双树生长策略,从目标点和起点同时生长随机树,加快收敛速度。仿真结果表明,相较于RRT,改进方法计算时间缩短18.1%~88.1%,随机树节点减少24.0%~90.6%。在真实环境下的实验对比验证了改进算法在路径长度、收敛时间等方面的优势。

采用统计线性回归的改进ATBI-GMPHD滤波

提出一种改进的自适应新生目标GM-PHD算法。该算法以存活目标的量测更新权值构建“似然函数”,通过该函数确定量测来源并对新生目标权值做重分配,有效解决了归一化失衡问题。在量测方程高度非线性情况下,引入统计线性回归方法对量测方程进行线性化近似,求解新生目标预测均值和协方差。仿真结果表明,在新生目标信息先验缺失时,改进后的算法具有良好的跟踪精度和较低的计算量。

肾透明细胞癌中双硫死亡核心基因SLC7A11的孟德尔随机化及生物信息学分析

目的分析溶质载体家族7成员11(SLC7A11)在肾透明细胞癌(ccRCC)发生、发展中的作用及其预后价值。方法采用两样本孟德尔随机化分析以识别与ccRCC风险存在因果关系的基因。使用来自UCSC Xena泛癌队列的RNA测序数据及临床数据分析SLC7A11的表达及预后意义。使用TCGA-KIRC数据(训练集)进行基因集富集分析(GSEA)。随后通过逐步Cox回归分析建立了基于SLC7A11的预后模型,并在E-MATB-1980队列(验证集)中进行了外部验证。结果孟德尔随机化分析显示,SLC7A11水平升高会加重ccRCC的患病风险(HR=1.27,95%CI:1.15~1.40,P<0.001)。SLC7A11在各种肿瘤中过表达,并与高T分期和较差的生存预后相关(P<0.05)。GSEA显示SLC7A11富集在增殖和转移相关通路,包括E2F和上皮-间质转化信号通路。SLC7A11预后模型在训练集(1、3、5年AUC=0.78、0.73、0.71)和验证集(1、3、5年AUC=0.70、0.71、0.72)中均显示出强大的预测性能。结论SLC7A11作为ccRCC的潜在生物标志物和治疗靶点,为精准医学提供了新视角。

基于随机化张量算法的红外弱小目标检测

为了降低基于张量低秩稀疏分解的红外弱小目标检测算法的计算复杂度,提升红外弱小目标的检测性能,将图像时空张量与随机化算法进行结合,提出了一种基于随机化张量算法的红外弱小目标检测算法。首先将红外图像序列构造成时空张量作为张量优化模型的输入,然后使用随机化张量算法求解张量优化模型,最后将计算得到的稀疏张量还原为图像,获得目标图像。结果表明,相比于传统基于低秩稀疏分解的算法,所提出的算法不仅计算速度快,而且具有较好的弱小目标检测性能。该研究为提升基于张量低秩稀疏分解的红外弱小目标检测算法的运算速度提供了参考。

基于三角形相似性的点云配准算法

针对点云配准过程易产生错误匹配对、点云配准精度低等问题,提出了一种基于三角形相似性的点云配准方法。三对正确的匹配点对在几何空间上形成的三角形一定满足相似三角形的一些性质,例如三角形三边成固定比例、三角形顶点的法线和平面法线的夹角固定。因此,可以利用这些性质有效地减少点云配准过程中错误匹配点对其影响。该方法首先计算点云中每个点的快速点特征直方图(FPFH)描述符,使用三角形相似性的方法进行特征匹配,通过奇异值(SVD)分解得到一个变换矩阵。实验结果表明,该方法与基于正态分布变换(NDT)算法与最近邻迭代(ICP)算法结合的点云配准算法相比,配准效率提升了15.3%,配准精度提升了18.2%。

基于激光SLAM的物流分拣机器人自主导航研究

物流分拣机器人工作环境的障碍物多,为此提出基于激光SLAM的物流分拣机器人自主导航研究方法。利用激光SLAM确定机器人工作环境中障碍物的分布情况;将目标偏置策略加入到RRT*算法中,通过设置固定概率和变概率的目标偏置策略,在遍历目标点时使路径节点更具导向性,更好地避免机器人与障碍物发生碰撞,再利用搜索随机树搜索其中的最短路径。对比实验表明:与常规方法相比,该方法可在起始点与目标点之间指导机器人按照最短路径行进,导航过程花费时间较短,使机器人自主导航的出错率和能耗均在5%左右。

基于椭圆随机超曲面模型CPHD滤波器的多扩展目标跟踪算法

复杂场景下多扩展目标跟踪在自动驾驶、目标识别等领域具有很高的应用价值。文中提出了一种基于椭圆随机超曲面模型(ERHM)的势概率假设密度(CPHD)滤波器。首先,基于有限集统计理论,利用CPHD滤波器建立多扩展目标的贝叶斯滤波框架;然后,采用ERHM描述扩展目标的量测源分布,并利用无迹变换嵌入CPHD滤波流程;最后,仿真实验结果表明,ERHM-CPHD滤波器对椭圆扩展目标的跟踪性能优于传统的伽马高斯逆威沙特CPHD滤波器,在杂波密度较高、目标新生的位置比较确定的场景或者扩展目标数目较多时,对扩展目标的参数估计更为准确。所提方法在高分辨率雷达多目标跟踪方面具备很好的运用前景。

基于随机有限集的多目标跟踪技术综述

随机有限集理论为多目标跟踪、多传感器融合和态势评估等问题提供了完整、统一的理论框架和解决方案。基于随机有限集的跟踪算法将多目标状态和量测建模为随机有限集,自然地引入航迹起始、终结机制,可实现目标数量和状态的同时估计。通过对随机有限集框架下的概率假设密度、带势概率假设密度、多目标多伯努利滤波器、扩展标签随机集滤波器和泊松多伯努利混合滤波器的研究进展进行详细梳理和综合对比,对基于随机有限集的多目标跟踪领域未来发展方向进行了分析和展望。

基于RRT-BZD算法的移动机器人路径规划

针对传统RRT算法在移动机器人路径规划中效率低、路径非最优的问题,提出一种改进的RRT-BZD算法,以提高RRT算法的收敛速度和算法的搜索效率。改进的RRT-BZD算法通过设置自适应目标偏向策略以及修剪冗余节点,加快了路径规划的收敛速度,减少了算法运行的时间,并且使用贝塞尔插值法使最终的路径更加平滑。在MATLAB仿真环境中分别对不同场景下的算法进行对比实验,实验结果表明:改进的RRT-BZD算法路径代价比传统RRT算法减少了7.93%,计算时间减少了20.28%,验证了改进算法的有效性和可行性。

基于随机历史集的有反馈MSIF目标识别方法

为提高复杂战场环境下的目标识别准确度,提出了一种分布式MSIF模型,并通过加入反馈信息流,对时域内的序贯信息进行处理。以经典D-S证据理论为基础,针对其不能处理高冲突证据的弊端,采用费雪耶兹洗牌方法,置乱泛传感器矩阵中的信息排序,生成随机历史集,并随着运算次数增加,算法反复迭代。通过改进算法,修正了由于高冲突证据过早出现所带来的识别结果偏差。数值算例表明,该方法既能提高信息利用率,同时可克服信息先入性陷阱的影响,准确度较高,且计算量较小,能有效减轻系统负担,适合MSIF目标识别中的大数据量处理。

DEGREE:一种基于Delaunay三角的任意群目标外形识别方法

集群目标相比单一甚至多目标表现出复杂时变集群特性,其外形估计与评价颇具挑战性。针对任意形状的集群目标外形估计与评价难题,本文提出了一种基于数据驱动的多传感器集群目标群形状建模与识别方法,以及一种群目标外形拟合度评判指标。所提算法由三个部分组成:首先,采用信息洪泛(Flooding)方法实现强连接的多传感器对视场中目标信息的采集与传播;其次,采用密度峰值聚类实现观测数据的聚类;最后,采用改进Delaunay三角网络算法实现群目标外形的拟合。所提群外形拟合度指标可用于对群目标外形估计准确度定量评价。通过与超曲面、随机矩阵等经典方法进行比较,证实了所提出算法的有效性和可靠性。

基于文化基因算法求解动态武器目标分配

针对动态武器目标分配(dynamic weapon target assignment,DWTA)问题,提出一种基于进化算法和局部搜索算法的文化基因算法(memetic algorithm,MA)。以最大化目标毁伤为目标,建立考虑能力约束、策略约束、资源约束、拦截可行性约束条件下的DWTA模型;引入虚拟排列进行编码以满足拦截可行性要求,设计将排列转化为实际分配方案的构造方法,给出算法运行过程中对随机事件的处理方法。通过与遗传算法(genetic algorithm,GA)、MA-GLS(memetic algorithm global local search)求解不同测试实例的对比仿真,结果表明,MA算法具有寻优速度快、优化能力强、稳定性好的优点。

Identification of novel drug targets for diabetic retinopathy:proteome-wide mendelian randomization and colocalization analyses

Background:Diabetic retinopathy(DR)urgently needs novel and effective therapeutic targets.Integrated analyses of plasma proteomic and genetic markers can clarify the causal relevance of proteins and discover novel targets for diseases,but no systematic screening for DR has been performed.Methods:Summary statistics of plasma protein quantitative trait loci(pQTL)were derived from two extensive genome-wide analysis study(GWAS)datasets and one systematic review,with over 100 thousand participants covering thousands of plasma proteins.DR data were sourced from the largest FinnGen study,comprising 10,413 DR cases and 308,633 European controls.Genetic instrumental variables were identified using multiple filters.In the two-sample MR analysis,Wald ratio and inverse variance-weighted(IVW)MR were utilized to investigate the causality of plasma proteins with DR.Bidirectional MR,Bayesian Co-localization,and phenotype scanning were employed to test for potential reverse causality and confounding factors in the main MR analyses.By systemically searching druggable gene lists,the ChEMBL database,DrugBank,and Gene Ontology database,the druggability and relevant functional pathways of the identified proteins were systematically evaluated.Results:Genetically predicted levels of 24 proteins were significantly associated with DR risk at a false discovery rate<0.05 including 11 with positive associations and 13 with negative associations.For each standard deviation increase in plasm protein levels,the odds ratios(ORs)for DR varied from 0.51(95%CI:0.36-0.73;P=2.22×10-5)for tubulin polymerization-promoting protein family member 3(TPPP3)to 2.02(95%CI:1.44-2.83;P=5.01×10-5)for olfactomedin like 3(OLFML3).Bidirectional MR indicated there was no reverse causality that interfered with the results of the main MR analyses.Four proteins exhibited strong co-localization evidence(PH4≥0.8):cytoplasmic tRNA synthetase(WARS),acrosin binding protein(ACRBP),and intercellular adhesion molecule 1(ICAM1)were negatively associated with DR risk,while neurogenic locus notch homolog protein 2(NOTCH2)showed a positive association.No confounding factors were detected between pQTLs and DR according to the phenotypic scan.Drugability assessments highlighted 6 proteins already in drug development endeavor and 18 novel drug targets,with metalloproteinase inhibitor 3(TIMP)currently in phase I clinical trials for DR.GO analysis identified 18 of 24 plasma proteins enriching 22 pathways related to cell differentiation and proliferation regulation.Conclusions:Twenty-four promising drug targets for DR were identified,including four plasma proteins with particular co-localization evidence.These findings offer new insights into DR's etiology and therapeutic targeting,exemplifying the value of genomic and proteomic data in drug target discovery.