基于频响分析的某车型复合材料后车门的模态参数识别分析

以某车型的复合材料后车门为研究对象,基于有限元分析方法,通过对复合材料车门在自由模态下的频响分析,识别出车门在一阶模态下的弯曲和扭转特性,为复合材料车门结构设计提供指导。

Clinical classification and gene mutation of Chinese probands with Charcot-Marie-Tooth disease Analysis of 57 cases

Charcot-Marie-Tooth （CMT） disease is the most common inherited peripheral neuropathic disorder. CMT is clinically and genetically heterogeneous. To date, 27 genes associated with the disease have been cloned. The present study carried out clinical classification according to clinical, electrophysiological and pathological features, conducted inheritance classification according to inheritance patterns, and performed mutation analysis of 13 CMT disease genes （PMP22, CX32, HSPB1, MNF2, MPZ, HSPB8, GDAP1, NFL, EGR2, SIMPLE, RAB7, LMNA, MTMR2） in 57 Chinese probands with CMT. Five cases of AD-CMT1 and 13 cases of sporadic CMT1 were diagnosed as CMT1A; five cases of X-CMT1, one case of X-CMT2 and one case of sporadic CMT1 were diagnosed as CMTXl; four cases of AD-CMT2 were diagnosed as CMT2F; one case of AD-CMT2 and one case of sporadic CMT2 were diagnosed as CMT2A2; one case of AD-CMT2 was diagnosed as CMT2L; one case of AD-CMT2 was diagnosed as CMT2J; one case of AR-CMT1 was diagnosed as CMT4A. Among the 57 CMT probands, seven genotypes were determined among 34 patients, with a detection rate of 59.6%. The results indicated that the clinical classification and inheritance classification are indispensable for selecting potential disease genes for mutation detection, and for efficient molecular diagnosis.

A novel transgenic mouse model of Chinese CharcotMarie-Tooth disease type 2L

We previously found that the K141N mutation in heat shock protein B8 （HSPB8） was responsible for Charcot-Marie-Tooth disease type 2L in a large Chinese family. The objective of the present study was to generate a transgenic mouse model bearing the K141N mutation in the human HSPB8 gene, and to determine whether this K141NHSPB8 transgenic mouse model would manifest the clinical phenotype of Charcot-Marie-Tooth disease type 2L, and consequently be suitable for use in studies of disease pathogenesis. Transgenic mice overexpressing K141N HSPB8 were generated using K141N mutant HSPB8 cDNA cloned into a pCAGGS plasmid driven by a human cytomegalovirus expression system. PCR and western blot analysis confirmed integration of the KI41NHSPB8 gene and widespread expression in tissues of the transgenic mice. The K141N HSPB8 transgenic mice exhibited decreased muscle strength in the hind limbs and impaired motor coordination, but no obvious sensory disturbance at 6 months of age by behavioral assessment. Electrophysiological analysis showed that the compound motor action potential amplitude in the sciatic nerve was significantly decreased, but motor nerve conduction velocity remained normal at 6 months of age. Pathological analysis of the sciatic nerve showed reduced myelinated fiber density, notable axonal edema and vacuolar degeneration in K141N HSPB8 transgenic mice, suggesting axonal involvement in the peripheral nerve damage in these animals. These findings indicate that the KI4mHSPB8 transgenic mouse successfully models Charcot-Marie-Tooth disease type 2L and can be used to study the pathogenesis of the disease.

Effect of the surface microstructure of arsenopyrite on the attachment of Sulfobacillus thermosulfidooxidans in the presence of dissolved As(Ⅲ)

Understanding bacterial adsorption and the evolution of biofilms on arsenopyrite with different surface structures is of great signific-ance to clarifying the mechanism of microbe-mineral interfacial interactions and the production of acidic mine drainage impacting the environ-ment.In this study,the attachment of Sulfobacillus thermosulfidooxidans cells and subsequent biofilm formation on arsenopyrite with different surface structures in the presence of dissolved As(Ⅲ)was studied.Arsenopyrite slices with a specific surface were obtained by electrochemic-al corrosion at 0.26 V.The scanning electronic microscopy-energy dispersion spectra analyses indicated that the arsenopyrite surface deficient in sulfur and iron obtained by electrochemical treatment was not favorable for the initial adsorption of bacteria,and the addition of As(Ⅲ)in-hibited the adsorption of microbial cells.Epifluorescence microscopy showed that the number of cells attaching to the arsenopyrite surface in-creased with time;however,biofilm formation was delayed significantly when As(Ⅲ)was added.

Prenatal diagnosis of spinocerebellar ataxia type 3/Machado-Joseph disease in China's Mainland A case report

Spinocerebellar ataxia type 3/Machado-Joseph disease （SCA3/MJD） is a progressive, currently untreatable and ultimately fatal ataxic disorder that belongs to the group of neurological disorders known as CAG-repeat or polyglutamine diseases. Here, we present the first prenatal diagnosis of SCA3/MJD in China's Mainland in a woman who was known to carry an expanded CAG-trinucleotide repeat in the MJD1 gene. After evaluating motivation and psychological tolerance of the couple, amniocentesis was performed after 14 weeks of gestation. Polymerase chain reactions followed by T-vector cloning and direct sequencing were employed to evaluate the CAG-repeat number of the fetal MJD1 gene. We identified a truncated CAG expansion of 78 repeats in the MJD1 gene of the fetus compared with 81 repeats in his mother.

Protein O-GlcNAcylation homeostasis regulates facultative heterochromatin to fine-tune sog-Dpp signaling during Drosophila early embryogenesis

Protein O-GlcNAcylation is a monosaccharide post-translational modification maintained by two evolutionarily conserved enzymes, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). Mutations in human OGT have recently been associated with neurodevelopmental disorders, although the mechanisms linking O-GlcNAc homeostasis to neurodevelopment are not understood. Here, we investigate the effects of perturbing protein O-GlcNAcylation using transgenic Drosophila lines that overexpress a highly active OGA. We reveal that temporal reduction of protein O-GlcNAcylation in early embryos leads to reduced brain size and olfactory learning in adult Drosophila. Downregulation of O-GlcNAcylation induced by the exogenous OGA activity promotes nuclear foci formation of Polycomb-group protein Polyhomeotic and the accumulation of excess K27 trimethylation of histone H3 (H3K27me3) at the mid-blastula transition. These changes interfere with the zygotic expression of several neurodevelopmental genes, particularly short gastrulation (sog), a component of an evolutionarily conserved sog-Decapentaplegic (Dpp) signaling system required for neuroectoderm specification. Our findings highlight the importance of early embryonic O-GlcNAcylation homeostasis for the fidelity of facultative heterochromatin redeployment and initial cell fate commitment of neuronal lineages, suggesting a possible mechanism underpinning OGT-associated intellectual disability.

土-膨润土隔离墙孔压静力触探非单调消散曲线研究（英文）

目的:土-膨润土隔离墙的水力特性可通过孔压静力触探试验进行评价。本文旨在研究土-膨润土隔离墙中孔压消散试验产生非单调孔压消散曲线的原因,并对现有计算固结系数与渗透系数的方法在土-膨润土隔离墙中的适用性进行分析。创新点:1.首次在土-膨润土隔离墙中测得非单调的孔压消散曲线;2.本文认为在土-膨润土隔离墙中测得非单调孔压消散曲线是由于探头贯入过程中在填料及其包裹的土块中产生的超孔压不一致引起的,并且由于填料的低渗透性,孔压上升的时间较长;3.比较不同方法的分析结果,并推荐结果与实测相近的计算方法作为工程应用。方法:1.通过室内一维固结试验和柔性壁渗透试验,分别获得墙体材料的固结系数和渗透系数;2.通过现场土-膨润土隔离墙的孔压静力触探试验与孔压消散试验,获得相应的力学参数与孔压消散曲线;3.分别采用不同方法对墙体材料的固结系数和渗透系数进行计算,并将计算结果与室内试验结果进行比较。结论:1.填料的非均质性导致探头贯入过程中产生的超孔压存在重分布,这使得土-膨润土隔离墙中产生了非单调孔压消散曲线,并且由于填料的低渗透性,测得孔压上升的时间较长;2.四种计算固结系数的方法中,有三种结果与室内一维固结试验结果相近,另一种结果则明显偏大;3.四种计算渗透系数的方法中,基于太沙基固结理论的关系式得到的结果与室内柔壁渗透试验结果相近,另两种经验公式得到的结果偏小,而基于探头贯入数据计算的渗透系数则偏大。

Targeted methylation sequencing reveals dysregulated Wnt signaling in Parkinson disease

Parkinson disease（PD） is a progressive neurodegenerative movement disorder. Both environmental and genetic factors play important roles in PD etiology. A number of environmental toxins cause parkinsonism in human and animal models. Genetic studies of rare early onset familial PD cases resulted in identification of disease-linked mutations in multiple genes. Nevertheless, the potential interaction between environment and genetics in PD pathogenesis remains largely unknown. We hypothesized that environmental factors induce abnormal epigenetic regulation that is involved in the pathogenesis of both familial and sporadic PD. We determined the global methylation status of 80,000e110,000 Cp G sites in each of the five sporadic PD patient brains and five age and postmodern interval matched control brains utilizing bisulfite padlock sequencing. Multiple genes involved in neurogenesis, particularly the ones in the Wnt signaling pathway, were hypermethylated in PD brains compared to their matched control brains. Consistent with the DNA methylation changes, marked reduction of protein expression was observed for four Wnt and neurogenesis related genes（FOXC1, NEURG2, SPRY1, and CTNNB1） in midbrain dopaminergic（DA） neurons of PD. The treatment of low concentration of 1-methyl-4-phenylpyridinium（MPPt） for cells resulted in downregulation of Wnt related genes. The study revealed an important link between the epigenetic disregulation of Wnt signaling and the pathogenesis and progression of PD.

Trafficking abnormality and ER stress underlie functional deficiency of hearing impairmentassociated connexin-31 mutants

Hearing impairment(HI)affects 1/1000 children and over 2%of the aged population.We have previously reported that mutations in the gene encoding gap junction protein connexin-31(Cx31)are associated with HI.The pathological mechanism of the disease mutations remains unknown.Here,we show that expression of Cx31 in the mouse inner ear is developmentally regulated with a high level in adult inner hair cells and spiral ganglion neurons that are critical for the hearing process.In transfected cells,wild type Cx31 protein(Cx31wt)forms functional gap junction at cell-cell-contacts.In contrast,two HIassociated Cx31 mutants,Cx31R180X and Cx31E183K resided primarily in the ER and Golgi-like intracellular punctate structures,respectively,and failed to mediate lucifer yellow transfer.Expression of Cx31 mutants but not Cx31wt leads to upregulation of and increased association with the ER chaperone BiP indicating ER stress induction.Together,the HI-associated Cx31 mutants are impaired in trafficking,promote ER stress,and hence lose the ability to assemble functional gap junctions.The study reveals a potential pathological mechanism of HI-associated Cx31 mutations.

Identification and characterization of human neuronal voltage-gated calcium channel gamma 3 subunit gene

By homologous expressed sequence tag (EST) searching, one EST (GenBank: W29095) was obtained, which shows 75% identity in 435 bp overlap with the coding sequence of mouse Cacng2 gene. A 1 545 bp cDNA fragment was obtained from the nested polymerase chain reaction (PCR) and rapid applification of cDNA end (RACE) reaction in the human brain prefrontal cortex cDNA library and the human brain Ready cDNA with the primers designed on W29095. The fragment contained a 948-bp open reading frame (ORF) encoding 315 amino acids, and was named CACNG3. As it was identical to a BAC clone (GenBank: AC004125) from chromosome 16p12-p13.1, the CACNG3 gene was mapped to human chromosome 16p12-p13.1, and the coding region was composed of 4 exons. Reverse transcription PCR (RT-PCR) analysis showed that the CACNG3 gene expressed in human adult brain and fetal brain. Single strand comformation polymorphism (SSCP) analysis was performed in 3 pedigrees with autosomal recessive retinitis pigmentosa, 8 pedigrees with autosomal

Genome-wide CRISPR activation screen identifies candidate receptors for SARS-CoV-2 entry

The outbreak of coronavirus disease 2019(COVID-19) caused by SARS-CoV-2 has created a global health crisis. SARS-CoV-2 infects varieties of tissues where the known receptor ACE2 is low or almost absent, suggesting the existence of alternative viral entry pathways. Here, we performed a genome-wide barcoded-CRISPRa screen to identify novel host factors that enable SARS-CoV-2 infection. Beyond known host proteins, i.e., ACE2, TMPRSS2, and NRP1, we identified multiple host components,among which LDLRAD3, TMEM30A, and CLEC4G were confirmed as functional receptors for SARS-CoV-2. All these membrane proteins bind directly to spike’s N-terminal domain(NTD). Their essential and physiological roles have been confirmed in either neuron or liver cells. In particular, LDLRAD3 and CLEC4G mediate SARS-CoV-2 entry and infection in an ACE2-independent fashion. The identification of the novel receptors and entry mechanisms could advance our understanding of the multiorgan tropism of SARS-CoV-2, and may shed light on the development of COVID-19 countermeasures.

石墨烯量子点修饰柔性硅纳米线阵列用于NO2检测

将化学刻蚀法与金属辅助刻蚀法相结合,制备了形貌统一、分布均匀的高质量柔性硅纳米线阵列结构,用石墨烯量子点对其表面进行修饰,得到了表面稳定且具有强载流子传输能力的柔性石墨烯量子点/硅纳米线核-壳结构阵列,用其制备气敏设备检测NO2.结果表明,基于该阵列的电阻式气敏设备对NO2的检测灵敏性及可重复性极高,检测浓度极限达20 mg/m3;不同弯曲度的柔性石墨烯量子点/硅纳米线阵列的气敏特性未大幅度降低,弯曲90o时响应电流峰值为未弯曲时的70%.

A COUPLED DYNAMIC MODEL OF BRAND ACCEPTANCE AND PROMOTIVE INFORMATION SPREADING

When people try to decide to buy or not to, they are often influenced by both their inherentopinions and the social marketing activities e.g. advertising, social news with strong point of view.Then people will make their final choice, or even convince other people to buy. After all, this is thebrand acceptance formation process. Factually, the dynamics of brand acceptance is essentially aninterwoven dynamics of endogenous opinion dynamics disturbed by an information diffusion process.To have a better understanding of the dynamics of brand acceptance, we propose and analyze a coupledagent-based dynamic model that combines the Majority-Rule-based Voter model in opinion dynamicswith the SI Model for information spreading to analyze the dynamics of brand acceptance in socialmedia. We focus on two important parameters in diffusion dynamics： the decayed transmission rate （fl）and the diffusion frequency （f）. When the system is stable, the order parameter of the system is theduration time （r）. In the absence of opinion interaction, the simulation results indicate that, when abrand tries to occupy a larger market share through social marketing approaches, it is always effectiveto let the opponent to be the propaganda target. While with the Majority-Rule-based Voter Modelincluded, we observe that the opinion interaction could have a dual function, which shows that a brandholding a small market share in the first place needs to adopt diverse marketing approaches accordingto different marketing environment types.