MicroRNA Mirn140 modulates Pdgf signaling during palatogenesis

Disruption of signaling pathways such as those mediated by sonic hedgehog (Shh) or platelet-derived growth factor (Pdgf) causes craniofacial abnormalities, including cleft palate. The role that microRNAs play in modulating palatogenesis, however, is completely unknown. We show that, in zebrafish, the microRNA Mirn140 negatively regulates Pdgf signaling during palatal development, and we provide a mechanism for how disruption of Pdgf signaling causes palatal clefting. The pdgf receptor alpha (pdgfra) 3' UTR contained a Mirn140 binding site functioning in the negative regulation of Pdgfra protein levels in vivo. pdgfra mutants and Mirn140-injected embryos shared a range of facial defects, including clefting of the crest-derived cartilages that develop in the roof of the larval mouth. Concomitantly, the oral ectoderm beneath where these cartilages develop lost pitx2 and shha expression. Mirn140 modulated Pdgf-mediated attraction of cranial neural crest cells to the oral ectoderm, where crest-derived signals were necessary for oral ectodermal gene expression. Mirn140 loss of function elevated Pdgfra protein levels, altered palatal shape and caused neural crest cells to accumulate around the optic stalk, a source of the ligand Pdgfaa. These results suggest that the conserved regulatory interactions of mirn140 and pdgfra define an ancient mechanism of palatogenesis, and they provide candidate genes for cleft palate.     

基于专家系统的防空火力分配模型

利用人工智能的原理,模拟军事专家的思维活动,建立基于专家系统的防空火力分配模型.该模型具有自学习功能,可自动获取和修改知识库中的知识,具有很好的实用性,可随时与用户进行交互.用产生式规则和原型表示可拦截条件及多目标优化分配原则等知识,采用了虚拟飞行时间作为综合威胁判断准则和可调整的分配始线和分配终线,能较好地满足实际需要.     

BP网络泛化能力改进研究

详细阐述了防止BP网络过度训练的方法,总结了常用的增强网络泛化能力的方法。并在此基础上,提出了基于主要影响因素和基于修正误差函数来增强网络泛化能力的方法,取得了良好的效果,提高了BP神经网络的适应性。     

一种新的模糊自校正控制学习算法

提出一种基于模糊竞争学习的模糊自校正控制方法.通过基于模糊竞争学习确定一种在线模糊辨识算法,在采用此模糊辨识方法对对象进行在线估计的基础上,用调节器实现参数的自动整定.为了验证所提方法的有效性,给出了非线性系统的控制结果.     

纳米复合技术改善工业ZnO压敏电阻避雷器微观结构及电性能的研究

运用纳米复合技术对工业ZnO压敏电阻避雷器的制备工艺的改进,研制出压敏电压340 V/mm,漏电流小于1μA,非线性系数大于56的压敏电阻器。根据ZnO晶粒生长动力学方程,研究了纳米复合ZnO粉体的烧结过程以及烧结过程中的晶粒生长规律,用扫描电镜和能谱对瓷体显微结构及面扫成分进行了分析,讨论了添加纳米复合粉的ZnO压敏电阻避雷器微观组织与综合性能的关系。实验表明,添加纳米复合粉体是降低大规模生产成本,提高经济效益,并得到综合性能优良产品的有效方法。     

公路交通事故黑点总体特征分析

采用改进的事故频数法选取了江苏、安徽两省部分二级以上公路事故黑点,运用事故数及致死事故率2个指标对事故黑点数据进行统计分析.得出了公路事故黑点总体特征表明:公路事故黑点所占里程短、事故数集中,事故致死率略大于一般路段;各等级公路事故黑点在事故时间分布、季节及气候影响、事故的道路线形分布等特征方面具有相似性,在事故类型分布、事故形态分布、事故空间分布等方面又具有不同特征.     

德士古渣油气化系统数学模拟

对德士古渣油气化系统进行了过程分析,建立了单元设备物料和热量衡算的数学模型,提出了计算气化炉微量组分的方法。运用序贯模块法对该系统进行了稳态模拟计算,结果同设计值和工厂值吻合较好。     

The emerging link between O-GlcNAcylation and neurological disorders

O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is involved in the regulation of many cellular cascades and neurological diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and stroke. In the brain, the expression of O-GlcNAcylation is notably heightened, as is that of O-linked N-acetylglucosaminyltransferase (OGT) and β-N-acetylglucosaminidase (OGA), the presence of which is prominent in many regions of neurological importance. Most importantly, O-GlcNAcylation is believed to contribute to the normal functioning of neurons; conversely, its dysregulation participates in the pathogenesis of neurological disorders. In neurodegenerative diseases, O-GlcNAcylation of the brain’s key proteins, such as tau and amyloid-β, interacts with their phosphorylation, thereby triggering the formation of neurofibrillary tangles and amyloid plaques. An increase of O-GlcNAcylation by pharmacological intervention prevents neuronal loss. Additionally, O-GlcNAcylation is stress sensitive, and its elevation is cytoprotective. Increased O-GlcNAcylation ameliorated brain damage in victims of both trauma-hemorrhage and stroke. In this review, we summarize the current understanding of O-GlcNAcylation’s physiological and pathological roles in the nervous system and provide a foundation for development of a therapeutic strategy for neurological disorders.     

A genome-wide association study in Han Chinese identifies new susceptibility loci for ankylosing spondylitis

To identify susceptibility loci for ankylosing spondylitis, we performed a two-stage genome-wide association study in Han Chinese. In the discovery stage, we analyzed 1,356,350 autosomal SNPs in 1,837 individuals with ankylosing spondylitis and 4,231 controls; in the validation stage, we analyzed 30 suggestive SNPs in an additional 2,100 affected individuals and 3,496 controls. We identified two new susceptibility loci between EDIL3 and HAPLN1 at 5q14.3 (rs4552569; P = 8.77 × 10(-10)) and within ANO6 at 12q12 (rs17095830; P = 1.63 × 10(-8)). We also confirmed previously reported associations in Europeans within the major histocompatibility complex (MHC) region (top SNP, rs13202464; P < 5 × 10(-324)) and at 2p15 (rs10865331; P = 1.98 × 10(-8)). We show that rs13202464 within the MHC region mainly represents the risk effect of HLA-B*27 variants (including HLA-B*2704, HLA-B*2705 and HLA-B*2715) in Chinese. The two newly discovered loci implicate genes related to bone formation and cartilage development, suggesting their potential involvement in the etiology of ankylosing spondylitis.     

Frequent mutations of chromatin remodeling genes in transitional cell carcinoma of the bladder

Transitional cell carcinoma (TCC) is the most common type of bladder cancer. Here we sequenced the exomes of nine individuals with TCC and screened all the somatically mutated genes in a prevalence set of 88 additional individuals with TCC with different tumor stages and grades. In our study, we discovered a variety of genes previously unknown to be mutated in TCC. Notably, we identified genetic aberrations of the chromatin remodeling genes (UTX, MLL-MLL3, CREBBP-EP300, NCOR1, ARID1A and CHD6) in 59% of our 97 subjects with TCC. Of these genes, we showed UTX to be altered substantially more frequently in tumors of low stages and grades, highlighting its potential role in the classification and diagnosis of bladder cancer. Our results provide an overview of the genetic basis of TCC and suggest that aberration of chromatin regulation might be a hallmark of bladder cancer.