近年来,复合材料层合板结构被广泛地应用于航空航天、军工、建筑工程等领域。但是,由于其几何尺寸的不准确性、材料参数的分散性、载荷环境的波动性等不确定性因素的影响,可能会对复合材料层合板结构的可靠性和安全性,以及系统的输出响...近年来,复合材料层合板结构被广泛地应用于航空航天、军工、建筑工程等领域。但是,由于其几何尺寸的不准确性、材料参数的分散性、载荷环境的波动性等不确定性因素的影响,可能会对复合材料层合板结构的可靠性和安全性,以及系统的输出响应产生重大影响。由于复合材料层合板的层间黏结不良、外部应力集中等因素,当复合材料层合板结构的能量释放速率达到层间断裂韧性时,就会发生分层。因此对复合材料层合板结构的分层可靠性进行分析具有重要的意义。目前,对于复合材料层合板结构的可靠性分析主要是采用一阶可靠性方法(first order reliability method,FORM)、二阶可靠性方法(second order reliability method,SORM)和重要性抽样方法(importance sampling,IS)等传统可靠性分析方法,并将其和蒙特卡罗模拟(Monte Carlo simulation,MCS)对比。但是,当复合材料结构不确定性维度高且复杂时,这些方法不仅计算效率太低,而且不能保证其计算精度。相比于传统的可靠性分析方法,可以利用基于自适应Kriging模型集成策略和主动学习函数结合蒙特卡罗模拟(adaptive Kriging-based Monte Carlo simulation,AK-MCS)的方法,对复合材料层合板结构进行可靠性分析。而直接概率积分方法(direct probability integral method,DPIM)具有更高的计算效率和精度,特别是对于高维度和复杂的可靠性分析问题。所以,本文采用AK-MCS方法和DPIM对模式Ⅰ、模式Ⅱ和混合Ⅰ/Ⅱ模式下的复合材料层合板结构分层的可靠度进行了研究。结果表明:DPIM和AK-MCS与传统可靠性分析方法相比具有更高的计算精度和计算效率,但是DPIM以其高效的计算效率脱颖而出,尽管其精度略低于AK-MCS,但在处理随机变量更多、非线性程度更高的混合Ⅰ/Ⅱ模式下的层合板结构分层的可靠性时展现出明显优势。综合考虑精度与时效性的平衡,DPIM能够准确地评估复合材料结构的可靠度,保障其在航天航空装备等领域的安全运行。展开更多
Multiple morphological abnormalities of the flagella(MMAF)represent a severe form of sperm defects leading to asthenozoospermia and male infertility.In this study,we identified a novel homozygous splicing mutation(c.8...Multiple morphological abnormalities of the flagella(MMAF)represent a severe form of sperm defects leading to asthenozoospermia and male infertility.In this study,we identified a novel homozygous splicing mutation(c.871-4 ACA>A)in the adenylate kinase 7(AK7)gene by whole-exome sequencing in infertile individuals.Spermatozoa from affected individuals exhibited typical MMAF characteristics,including coiled,bent,short,absent,and irregular flagella.Transmission electron microscopy analysis showed disorganized axonemal structure and abnormal mitochondrial sheets in sperm flagella.Immunofluorescence staining confirmed the absence of AK7 protein from the patients’spermatozoa,validating the pathogenic nature of the mutation.This study provides direct evidence linking the AK7 gene to MMAF-associated asthenozoospermia in humans,expanding the mutational spectrum of AK7 and enhancing our understanding of the genetic basis of male infertility.展开更多
Aimed at the problem of the low computational efficiency of the existing urethral-valve reliability analysis,an efficient reliability analysis method of the wireless energy-transmitting urethral-valve(WETUV)was propos...Aimed at the problem of the low computational efficiency of the existing urethral-valve reliability analysis,an efficient reliability analysis method of the wireless energy-transmitting urethral-valve(WETUV)was proposed.The method is called FTA-AK-SS,based on the active learning Kriging(AK)model,subset simulation(SS)algorithm,and fault tree analysis(FTA).According to the principle of FTA,we established the fault tree model of the WETUV to determine its minimum cut set and bottom events.Then we defined the random variables affecting its reliability.The U learning function was used to selectively add the sample points of random variables to update the initial Kriging surrogate model.At the same time,combined with the SS algorithm,the reliability and sensitivity analyses of the WETUV were realized.The result shows that compared with the traditional Monte Carlo simulation and FTA-Kriging-SS methods,the proposed method significantly improves the calculation efficiency of the WETUV under the premise of ensuring calculation accuracy.The reliability of the WETUV is greatly affected by the rubber pad’s aging,the receiver coil’s corrosion,and the position deviation.This study can provide a new way to realize a high-efficiency reliability calculation and analysis for urethral valves.展开更多
Medically assisted reproduction(MAR)techniques are highly dependent on the sperm quantity and quality.Low sperm concentrations can be bypassed at least to some point by the usage of more sophisticated MAR techniques l...Medically assisted reproduction(MAR)techniques are highly dependent on the sperm quantity and quality.Low sperm concentrations can be bypassed at least to some point by the usage of more sophisticated MAR techniques like intracytoplasmic sperm injection(ICSI).Compared to this,disruptions in established indicators of sperm quality like motility or morphology pose greater challenges for the therapy of couple infertility.展开更多
文摘近年来,复合材料层合板结构被广泛地应用于航空航天、军工、建筑工程等领域。但是,由于其几何尺寸的不准确性、材料参数的分散性、载荷环境的波动性等不确定性因素的影响,可能会对复合材料层合板结构的可靠性和安全性,以及系统的输出响应产生重大影响。由于复合材料层合板的层间黏结不良、外部应力集中等因素,当复合材料层合板结构的能量释放速率达到层间断裂韧性时,就会发生分层。因此对复合材料层合板结构的分层可靠性进行分析具有重要的意义。目前,对于复合材料层合板结构的可靠性分析主要是采用一阶可靠性方法(first order reliability method,FORM)、二阶可靠性方法(second order reliability method,SORM)和重要性抽样方法(importance sampling,IS)等传统可靠性分析方法,并将其和蒙特卡罗模拟(Monte Carlo simulation,MCS)对比。但是,当复合材料结构不确定性维度高且复杂时,这些方法不仅计算效率太低,而且不能保证其计算精度。相比于传统的可靠性分析方法,可以利用基于自适应Kriging模型集成策略和主动学习函数结合蒙特卡罗模拟(adaptive Kriging-based Monte Carlo simulation,AK-MCS)的方法,对复合材料层合板结构进行可靠性分析。而直接概率积分方法(direct probability integral method,DPIM)具有更高的计算效率和精度,特别是对于高维度和复杂的可靠性分析问题。所以,本文采用AK-MCS方法和DPIM对模式Ⅰ、模式Ⅱ和混合Ⅰ/Ⅱ模式下的复合材料层合板结构分层的可靠度进行了研究。结果表明:DPIM和AK-MCS与传统可靠性分析方法相比具有更高的计算精度和计算效率,但是DPIM以其高效的计算效率脱颖而出,尽管其精度略低于AK-MCS,但在处理随机变量更多、非线性程度更高的混合Ⅰ/Ⅱ模式下的层合板结构分层的可靠性时展现出明显优势。综合考虑精度与时效性的平衡,DPIM能够准确地评估复合材料结构的可靠度,保障其在航天航空装备等领域的安全运行。
文摘目的基于生物信息学与机器学习方法探讨多囊卵巢综合征(polycystic ovary syndrome,PCOS)关键基因,并在临床水平进行验证,同时筛选对相关基因起调控作用的中药。方法应用GEO数据库获取4个数据集,使用R软件包“Limma”和加权基因共表达网络分析(weighted gene co-expression network analysis,WGCNA)筛选PCOS组与健康对照组的差异表达基因,并对其进行功能富集和细胞免疫浸润分析。应用机器学习算法获取PCOS关键基因,绘制列线图,建立受试者工作特征(receiver operator characteristic,ROC)曲线评估列线图与每个关键基因识别PCOS的能力及特异性和敏感性。收集临床PCOS患者外周血单个核细胞,对关键基因表达量与PCOS识别情况进行临床验证。通过COREMINE数据库、古今医案云平台预测潜在调控PCOS的中药,并分析其性味归经及功效。结果4个数据集共获得42个样本,其中PCOS组21个样本,健康对照组21个样本。共获得差异基因127个,基因本体(gene ontology,GO)分析显示差异基因与肾上腺髓质素受体信号过程、细胞间桥、类固醇结合等有关;京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)分析显示差异基因与核因子-κB(nuclear factor-κB,NF-κB)介导的肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)信号传导、血管生成、白细胞介素-2(interleukin-2,IL-2)-信号转导和转录激活因子5(signal transducer and activator of transcription 5,STAT5)信号等相关。进一步进行细胞免疫浸润,发现PCOS组γδT细胞、单核细胞、激活的肥大细胞水平升高,浆细胞、CD4初始T细胞、激活的自然杀伤(natural killer,NK)细胞水平降低。最小绝对收缩和选择算子(logistic least absolute shrinkage and selection operator,LASSO)-Cox比例风险模型(Cox proportional-hazards model,COX)回归筛选11个关键靶点,包括AK4、DEPP1、DUOX2、FGG、GAREM1、PLOD2、SLC41A2、SPIN4、THNSL1、TMEM187、ZNF443,PCOS组关键基因的表达量均低于对照组(P<0.05),单个关键基因识别PCOS的曲线下面积(area under urve,AUC)为0.76~0.90,诺莫图识别PCOS的AUC为0.98。临床数据验证共纳入PCOS组12例,健康对照组12例,PCOS组AK4、ZNF443、DUOX2、DEPP1、FGG、SLC41A2、SPIN4与TMEM187的基因表达量均低于健康对照组(P<0.05),应用诺莫图验证对PCOS的识别,AUC为1。预测到与差异基因相关的中药85味,中药的四气以寒、温、平为主,五味以苦、甘、辛味为主,归经以肝、肺、胃经为主,功效以清热解毒、理气为主。结论AK4、DEPP1、DUOX2、FGG、GAREM1、PLOD2、SLC41A2、SPIN4、THNSL1、TMEM187、ZNF443可能是识别PCOS的潜在关键生物标志物以及对潜在治疗中药的预测二者为PCOS的诊断和治疗提供了新思路。
基金supported by the National Key Research and Development Program of China(No.2021YFC2700202,No.2022YFA0806303,and No.2022YFC2702601)the Global Select Project of the Institute of Health and Medicine,Hefei Comprehensive National Science Center(DJK-LX-2022010)the Joint Fund for New Medicine of USTC(YD9100002034).
文摘Multiple morphological abnormalities of the flagella(MMAF)represent a severe form of sperm defects leading to asthenozoospermia and male infertility.In this study,we identified a novel homozygous splicing mutation(c.871-4 ACA>A)in the adenylate kinase 7(AK7)gene by whole-exome sequencing in infertile individuals.Spermatozoa from affected individuals exhibited typical MMAF characteristics,including coiled,bent,short,absent,and irregular flagella.Transmission electron microscopy analysis showed disorganized axonemal structure and abnormal mitochondrial sheets in sperm flagella.Immunofluorescence staining confirmed the absence of AK7 protein from the patients’spermatozoa,validating the pathogenic nature of the mutation.This study provides direct evidence linking the AK7 gene to MMAF-associated asthenozoospermia in humans,expanding the mutational spectrum of AK7 and enhancing our understanding of the genetic basis of male infertility.
基金Foundation item:the National Natural Science Foundation of China(No.52075101)the Natural Science Foundation of Guangdong Province(No.2017A030313265)Guangzhou Scientific Research Plan(No.201904010184)。
文摘Aimed at the problem of the low computational efficiency of the existing urethral-valve reliability analysis,an efficient reliability analysis method of the wireless energy-transmitting urethral-valve(WETUV)was proposed.The method is called FTA-AK-SS,based on the active learning Kriging(AK)model,subset simulation(SS)algorithm,and fault tree analysis(FTA).According to the principle of FTA,we established the fault tree model of the WETUV to determine its minimum cut set and bottom events.Then we defined the random variables affecting its reliability.The U learning function was used to selectively add the sample points of random variables to update the initial Kriging surrogate model.At the same time,combined with the SS algorithm,the reliability and sensitivity analyses of the WETUV were realized.The result shows that compared with the traditional Monte Carlo simulation and FTA-Kriging-SS methods,the proposed method significantly improves the calculation efficiency of the WETUV under the premise of ensuring calculation accuracy.The reliability of the WETUV is greatly affected by the rubber pad’s aging,the receiver coil’s corrosion,and the position deviation.This study can provide a new way to realize a high-efficiency reliability calculation and analysis for urethral valves.
文摘Medically assisted reproduction(MAR)techniques are highly dependent on the sperm quantity and quality.Low sperm concentrations can be bypassed at least to some point by the usage of more sophisticated MAR techniques like intracytoplasmic sperm injection(ICSI).Compared to this,disruptions in established indicators of sperm quality like motility or morphology pose greater challenges for the therapy of couple infertility.
