SHEsis,a powerful software platform for analyses of linkage disequilibrium,haplotype construction,and genetic association at polymorphism loci

In multiloci-based genetic association studies of complex diseases, a powerful and high efficient tool for analyses oflinkage disequilibrium (LD) between markers, haplotype distributions and many chi-square/p values with a large numberof samples has been sought for long. In order to achieve the goal of obtaining meaningful results directly from raw data,we developed a robust and user-friendly software platform with a series of tools for analysis in association study withhigh efficiency. The platform has been well evaluated by several sets of real data.

Recent progress in the study of Hedgehog signaling

The Hedgehog （Hh） family of secreted signaling proteins plays a critical role in regulating the development of several tissues and organ systems. The ability of Hh proteins to exert their biological effects is regulated by a series of post-translational processes. These processes include an intramolecular cleavage, covalent addition of cholesterol and/or palmitate, and conversion into a multimeric freely diffusible form. The processing of Hh proteins affects their trafficking, potency, and ability to signal over several cell diameters. Here we review the current understanding of the Hh signaling mechanisms that govern the establishment of the Hh gradient and the transduction of the Hh signal in the light of recent data.

Targeted inhibition of Notch1 gene enhances the killing effects of Paclitaxel on triple-negative breast cancer cells

Objective:To study the influence of targeted inhibition of Notch1 gene on the killing effects of Paclitaxel on triple-negative breast cancer cells.Methods:The triple-negative [estrogen receptor(ER)/progesterone receptor(PR)/human epidermal growth factor receptor 2(Her2)] breast cancer cell line MDA-MB-231 and ER/PR/HER-2-positive breast cancer cell line MCF-7 were cultured,transfected with Notch1-si RNA-overexpression plasmid and blank plasmid,and treated with different concentrations of paclitaxel,and then the cell proliferation activity and apoptosis rate as well as the m RNA expression of Caspase-3,Caspase-9 and Bcl-2 were determined.Results:Paclitaxel could decrease the MDA-MB-231 and MCF-7 cell proliferation activity as well as Bcl-2 mRNA expression,and increase MDA-MB-231 and MCF-7 cell apoptosis rate as well as Caspase-3 and Caspase-9 mRNA expression in dosedependent manners;with the same dose of paclitaxel treatment,the inhibitory effects on MDAMB-231 cell proliferation activity and Bcl-2 m RNA expression as well as the promoting effects on MDA-MB-231 cell apoptosis and mR NA expression of Caspase-3 and Caspase-9 were weaker than those on MCF-7 cell;after 0.5 μM paclitaxel combined with Notch1-siRNA treatment,MDA-MB-231 cell proliferation activity and Bcl-2 mRNA expression were significantly lower than those after 0.5 μM paclitaxel combined with control plasmid treatment while cell apoptosis rate and mR NA expression of Caspase-3 and Caspase-9 were higher than those after 0.5 μM paclitaxel combined with control plasmid treatment.Conclusions:Targeted inhibition of Notch1 gene may enhance the killing effects of paclitaxel on triple-negative breast cancer cells by up-regulating the expression of Caspase-3 and Caspase-9 and inhibiting the expression of Bcl-2.

Effect and mechanism of baicalin and geniposide on excitotoxicity of acute cerebral ischemia

OBJECTIVE Based on the methods of microdialysis,HPLC-MS/MS and gene chip tech.nology,the mechanism of Baicalin and Geniposide(BC/GP) against excitatory amino acid toxicity in ce.rebral ischemia was studied.This will provide guidance for the clinical application of BC/GP and the study of excitatory amino acid toxicity in cerebral ischemia.METHODS(1) Microdialysis technique and HPLC-MS/MS was performed to study the pharmacodynamics of BC/GP against cerebral ischemia.(1)18 SD rats with body weight of(280±20) g were randomly divided into control group,treatment groups with BC/CP at low dose,medium dose and high dose(equal to the dosage of crude drugs for 30 mg·kg^(-1),45 mg·kg^(-1) and 60 mg·kg^(-1) respectively).Rats in each group were given intragastric administration for seven days to establish cerebral ischemia model.Then,microdialysis probe was applied to collect cerebrospinal fluid from hippocampus before and after cerebral ischemia.(2) First,we established the HPLC-MS/MS method for measuring drugs and excitatory amino acids.Then we detected the microdi.alysis samples and observed their changes in animals.(2) The mechanism of BC/GP against excitatory toxicity of cerebral ischemia were observed at gene level by chip technique.(1) 16 SD rats with body weight of 240±20 g were randomly divided into sham group,model group,treatment group of BC(60 mg·kg^(-1)),treatment group of GP(60 mg·kg^(-1)) and treatment group of BC/GP(7:3)(60 mg·kg^(-1)).Rats in eachgroup were given intragastric administration for seven days to establish cerebral ischemia model.Then the rats were sacrificed,and the hippocampus were rapidly harvested and stored at-80℃ for further detection.(2) After the quality inspection of the hippocampal,the qualified samples were subjected to detect the levels of neurotransmitter receptor gene in the ischemic of rats by gene chip technology.Finally,the results were analyzed by the method of ΔΔCt.RESULTS(1) Only three compounds includ.ed GP,glutamic acid and aspartic acid were detected in microdialysis samples by HPLC-MS/MS.The concentration of GP increased and lasted for 120 min with a significant dose-dependent after cerebral ischemia.Compared with low dose group,the AUC(0-t),MRT(0-∞),Cmax and t1/2 z in high-dose group showed significant difference(P<0.01).Compared with the model group,the levels of glutamic acid and aspartic acid in the treatment groups decreased significantly,especially in the middle and high dose groups.(2)89 genes in the neurotransmitter receptor gene signaling pathway were detected by gene chip technol.ogy.There were 22 genes with |Fold Regulation| >1.5 in the model group,compared with the sham group.Five of the 22 genes showed statistically significant differences,including Grin2 c(2.9026),Chrna7(-1.5877),and Tacr2(-1.7695).Htr3 a(-1.8172) and Grm6(-2.3527).There were 5 genes with |Fold Regulation|>1.5 in the BC group,compared with the model group,Two of them exhibited statistically significant differences,including Brs3(1.797)and Grin2 c(-1.7979).There were 14 genes with |Fold Reg.ulation| >1.5 in the GP group,compared with the model group.Three of them displayed statistically significant differences,including Hcrtr2(-1.6584),Sctr(-3.8524) and Grin2 c(-4.8408).Compared with model group,the genes of |Fold Regulation| >1.5 in BC/GP(7:3) group are 5,and only one of them showed a significant differences.CONCLUSION(1) After administration of BC and GP,GP can cross the blood-brain barrier and reduce the release of excitatory amino acids in the hippocampus.(2) BC/GP can inhibit the interaction between excitatory amino acids and excitatory amino acid receptors and attenuate the toxicity of excitatory amino acids by down-regulating the expression of glutamic acid receptor Grin2 c gene.(3) BC/GP may exert their brain protection effect by reducing the release of excit.atory amino acids and inhibiting the expression of excitatory amino acid receptors.

Anti-inflammatory Effect of Heat-sensitive Moxibustion via the NF-κB Signaling Pathway on Cerebral Ischemia/Reperfusion Injury in Rats

Ischemic stroke is universally acknowledged as a common cause of long-term disability or even death. Suspended moxibustion, an indirect form of moxibustion, is when moxibustion is placed superficially over the skin without being in contact with it. Some researchers have used this method to treat stroke patients, but strong evidence of its therapeutic effectiveness is lacking. However, the effect of traditional suspended moxibustion has recently been improved with the development of heat-sensitive suspended moxibustion. Our previous studies showed that moxibustion for 35 min provided a more effective treatment strategy than moxibustion for 15 min, and moxibustion by 35 min with tail temperature increase had a better outcome than that without, however, the mechanism underlying the effect is not clear. In this study, we treated the stroke rats with moxibustion by 35min and divided them into non-heat sensitive moxibustion(NHSM) group and heat sensitive moxibustion (HSM) group according to difference in the tail temperature increase, then we compared the effect and investigated the mechanisms between NHSM and HSM. We found that HSM significantly decreased tail-flick latency, increased neurological function score, decreased infarct volume, reduced inflammatory cells, decreased the expression of inflammatory factor ICAM-1 and reduced the expression of NF-κB p65 and p-IKKα/β in rats with focal cerebral ischemia/reperfusion injury. Our experimental findings revealed that HSM exerted its anti-inflammatory and neuroprotective effects from MCAO-induced injury by decreasing the expression of the NF-κB signaling pathway.

Simulation of the emission lines radiated from cataclysmic variables

Cataclysmic variables are special celestial bodies because they have particular light curves and spectra.The mechanisms for generating emission lines radiated from dwarf novae in their quiescent phases are studied.We assume that the incident radiation field which is emitted by a hot source（white dwarf and boundary layer）irradiates the gaseous layer evaporated from the accretion disk,and the emission lines are radiated from the gas.We model the fluxes of emission lines by using the photoionization code CLOUDY.Using this method,we input some reasonable parameters and get a series of simulated spectra.In order to find a simulated spectrum which is the best fit to an observed spectrum,we use a cross-correlation method to match them.After the calculation,we use the approximation that the parameters of the simulated spectrum can simulate the observed spectrum.Finally,we learn more about the physical conditions of the system.

硫掺杂铁基单原子催化剂结构与催化活性的密度泛函理论研究

通过密度泛函理论计算研究了硫原子掺杂对铁基单原子催化剂结构稳定性和催化活性的影响.采用结构优化和自由能计算的方法,评估了硫掺杂构型的热力学和电化学稳定性.结果表明:硫原子呈卫星式排布环绕单原子催化剂活性位点,形成稳定的催化剂结构,并对活性位点的电子结构进行调控.进一步比较了硫掺杂前后的催化活性,结果显示硫掺杂能够显著降低氧还原反应的过电势,特别是对称性破缺的体系表现出最低的过电势.

Observation of Charge Density Wave in Layered Hexagonal Cu1.89Te Single Crystal

We report comprehensive transport, electron microscopy and Raman spectroscopy studies on transition-metal chalcogenides Cu1.89Te single crystals. The metallic Cu1.89Te displays successive metal-semiconductor transitions at low temperatures and almost ideal linear MR when magnetic field up to 33 T. Through the electron diffraction patterns, the stable room-temperature phase is identified as a 3 × 3 × 2 modulated superstructure based on the Nowotny hexagonal structure. The superlattice spots of transmission electron microscopy and scanning tunneling microscopy clearly show the structural transitions from the room-temperature commensurate Ⅰ phase, named as C-Ⅰ phase, to the low temperature commensurate Ⅱ(C-Ⅱ) phase. All the results can be understood in terms of charge density wave(CDW) instability, yielding intuitive evidences for the CDW formations in Cu1.89Te. The additional Raman modes below room temperature further reveal that the zone-folded phonon modes may play an important role on the CDW transitions. Our research sheds light on the novel electron features of Cu1.89Te at low temperature, and may provide potential applications for future nano-devices.

草酸浓度调控对水系锌离子电池正极材料NH_(4)V_(4)O_(10)合成的优化

采用一步水热法,调整不同的草酸含量制备了NH_(4)V_(4)O_(10)(NVO)样品,并研究其作为水系锌离子电池正极材料的电化学性能.实验发现:草酸的浓度在决定样品组成上起到了关键性作用.当浓度较低时,得到NVO和(NH_(4))_(2)V_(4)O_(9)的混合相;草酸浓度过高则会导致VO_(2)的生成.当偏钒酸铵与草酸的摩尔比保持在1∶1时,成功合成了纯相NVO.电化学测试结果表明:纯相NVO在0.2 A·g^(-1)的电流密度下,比容量达到了479.3 mAh·g^(-1),性能显著优于其它样品.此外,该材料在0.1 mV·s^(-1)的扫描速率下,赝电容贡献率高达82.48%.

白屈菜红碱对人卵巢癌SKOV3细胞迁移、侵袭和上皮-间质转化的影响

目的:探讨白屈菜红碱(CHE)对人卵巢癌SKOV3细胞迁移、侵袭和上皮-间质转化(EMT)的抑制作用,阐明其相关作用机制。方法:体外培养SKOV3细胞,分为对照组和2.5、5.0、10.0、20.0及40.0μmol·L^(-1)CHE组,采用噻唑蓝(MTT)法检测各组细胞增殖抑制率。体外培养SKOV3细胞,分为对照组、转移生长因子β1(TGF-β1)组、TGF-β1+5μmol·L^(-1)CHE组和TGF-β1+10μmol·L^(-1)CHE组,采用细胞划痕实验检测各组细胞迁移率,Transwell小室实验检测各组细胞中迁移细胞数和侵袭细胞数,Westren blotting法检测各组细胞中E-钙黏蛋白(E-cadherin)、N-钙黏蛋白(N-cadherin)和波形蛋白(Vimentin)蛋白表达水平,免疫荧光染色法检测各组细胞中E-cadherin和N-cadherin荧光强度。结果:MTT法,与对照组比较,5.0、10.0、20.0和40.0μmol·L^(-1)CHE组细胞增殖抑制率明显升高(P<0.05或P<0.01)。细胞划痕实验,与对照组比较,TGF-β1组细胞迁移率明显升高(P<0.01);与TGF-β1组比较,TGF-β1+5μmol·L^(-1)CHE组和TGF-β1+10μmol·L^(-1)CHE组细胞迁移率明显降低(P<0.01)。Transwell小室实验,与对照组比较,TGF-β1组细胞中迁移细胞数和侵袭细胞数明显增加(P<0.05);与TGF-β1组比较,TGF-β1+5μmol·L^(-1)CHE组和TGF-β1+10μmol·L^(-1)CHE组细胞中迁移细胞数和侵袭细胞数明显减少(P<0.01)。Westren blotting法,与对照组比较,TGF-β1组细胞中E-cadherin蛋白表达水平明显降低(P<0.01),N-cadherin和Vimentin蛋白表达水平明显升高(P<0.05或P<0.01);与TGF-β1组比较,TGF-β1+5μmol·L^(-1)CHE组和TGF-β1+10μmol·L^(-1)CHE组细胞中E-cadherin蛋白表达水平明显升高(P<0.01),N-cadherin和Vimentin蛋白表达水平明显降低(P<0.01)。免疫荧光染色,与对照组比较,TGF-β1组细胞中E-cadherin荧光强度明显降低,N-cadherin荧光强度明显升高;与TGF-β1组比较,TGF-β1+5μmol·L^(-1)CHE组和TGF-β1+10μmol·L^(-1)CHE组细胞中E-cadherin荧光强度明显升高,N-cadherin荧光强度明显降低。结论:CHE能够抑制人卵巢癌SKOV3细胞增殖、迁移、侵袭和EMT。

软件漏洞模糊测试的关键分支探索及热点更新算法

在软件开发及应用中,由于具有可复现性,模糊测试能够帮助发现漏洞和有针对性地对漏洞成因进行分析。为了解决模糊测试过程的效率及测试力度等问题,提出了软件漏洞模糊测试的关键分支探索及热点更新算法。该方法通过捕获、分析和利用受检程序在处理测试用例时的执行位置的关键信息,以指导模糊测试过程的探索方向和测试用例的生成。实验结果表明,提出的方法相较于传统随机发散的模糊测试方法在漏洞发现能力上有较大提升,在Otfcc、Swftools等14个开源程序中发现了100余个未被公布的漏洞,为模糊测试用于软件漏洞检测提供了新的可靠途径。

T22/TP304H异种钢焊接接头性能分析与剩余寿命评估

异种钢焊接在亚临界锅炉中被广泛运用,其焊接接头性能会直接影响锅炉的运行安全和服役寿命。针对已服役20万小时以上的锅炉中带垫板T22/TP304H异种钢焊接接头,采用微观组织观察、常温与高温拉伸试验以及高温持久试验等方法,全面评估了焊接接头的组织形态、力学性能和耐久性。结果表明,TP304H母材及焊缝中有析出物聚集现象,易诱发焊接区域萌生裂纹;长期服役的接头拉伸强度低于ASME标准要求的最低值,力学性能出现较大程度的衰退;通过温度曲线推算法估算,焊接接头的剩余寿命为29 745 h,但其运行可靠性已显著降低,应对接头部位进行检修并加强后期巡检工作。该研究可为T22/TP304H异种钢焊接头的组织与性能研究和设备后续的安全运行提供理论参考。

Gut microbiota modulating intestinal stem cell differentiation

Proliferation and differentiation of intestinal stem cell(ISC)to replace damaged gut mucosal epithelial cells in inflammatory states is a critical step in ameliorating gut inflammation.However,when this disordered proliferation continues,it induces the ISC to enter a cancerous state.The gut microbiota on the free surface of the gut mucosal barrier is able to interact with ISC on a sustained basis.Micro-biota metabolites are able to regulate the proliferation of gut stem and progenitor cells through transcription factors,while in steady state,differentiated colono-cytes are able to break down such metabolites,thereby protecting stem cells at the gut crypt.In the future,the gut flora and its metabolites mediating the regulation of ISC differentiation will be a potential treatment for enteropathies.

人字齿行星齿轮系统激励参数二维域界特性

为探究人字齿行星齿轮系统激励参数二维域界特性,课题组构建了系统的平移-扭转动力学模型,运用Runge-Kutta法对消除刚体位移和量纲一化的系统微分方程组进行数值求解,基于离散空间域胞映射法绘制了啮合阻尼比与太阳轮输入转速和太阳轮输入功率构成的二维域界图,并结合位移分岔图、FFT频谱图、相图和Poincaré映射对系统激励参数二维域界特性进行分析。结果表明:在满足系统工况条件下,适当增大啮合阻尼比可使系统由混沌运动转变为周期运动;啮合阻尼比较小时,系统对太阳轮输入转速变化敏感,提高太阳轮输入转速可使系统进入稳定1周期运动,减轻系统振动响应;太阳轮输入功率较小时,系统处于大范围混沌运动区域,通过增加太阳轮输入功率,系统更趋向于稳定周期运动,提高系统运行稳定性。研究结果可为人字齿行星齿轮系统选择稳定运行的激励参数范围提供参考。

基于离散逆Preisach模型的磁悬浮系统非线性补偿研究

磁悬浮平台控制中,电磁铁铁芯材料的磁滞特性会很大程度影响控制精度,补偿磁滞特性是磁悬浮精密控制系统中必不可少的一部分,为了实现对磁悬浮精密控制系统中磁滞非线性的补偿,课题组使用离散逆Preisach模型构造了一个补偿器。首先建立了离散逆Preisach模型,再依据磁滞补偿原理,构造补偿器;根据逆模型的曲线形状,建立了基于双曲正切的分布函数验证离散逆Preisach模型构造的合理性;最后使用非负最小二乘法辨识模型。结果表明离散逆Preisasch模型描述电磁铁逆磁滞回线的最大误差为0.3%。所构造的补偿器具有良好的补偿效果,为磁悬浮系统的磁滞补偿提供了一种可行方案。

基于混合粒子群算法的圆柱型电磁铁优化设计

为了解决当电磁铁外型相同如何使电磁力最大的问题,将现有电磁铁设计思路应用到圆柱型电磁铁设计中,并采用改进的混合粒子群方法优化电磁铁内部结构参数。运用等效磁路法推导出电磁铁数学模型,并通过Maxwell有限元仿真对比验证准确性,然后采用单目标优化方法,得到影响电磁力的参数,最后采用改进的粒子群算法进行多目标优化,得到优化后的参数值。得到的几组优化数据表明:多目标优化方法得到的有效工作区域电磁力更大,仿真结果表明优化后的电磁力综合提高20%,证明优化方法有效。

热风干燥和冷冻干燥对西洋参外观、显微特征和人参皂苷含量影响的比较研究

Purpose Our purpose was to compare the difference between hot-air dried American ginseng(HDAG)(Panacis Quinquefolii Radix)and freeze-dried American ginseng(FDAG)(Panacis Quinquefolii Radix)and provide a better drying approach for improv-ing the quality of American ginseng(Panacis Quinquefolii Radix).Methods In our present study,we compared the appearance features of HDAG and FDAG using a CR-410 colorimeter and scanning electron microscopy.Furthermore,we qualitatively and quantitatively determined ginsenosides in HDAG and FDAG by using UPLC-Q Exactive Orbitrap-MS/MS and high-performance liquid chromatography.Results Our present results showed that compared to the hot-air drying method,freeze-drying(FD)has obvious advantages in not only good appearances but also higher bioactive constituents for drying the American ginseng(Panacis Quinquefolii Radix).Conclusion FD is beneficial for the retention of ginsenosides in American ginseng(Panacis Quinquefolii Radix)and also helpful for maintaining the bioactive effects of this functional food.

电伴热和保温材质对取水装置防冻性能实验研究

目前,高寒高海拔地区的农牧民依旧存在季节性饮水不便的问题,传统的末端取水装置因严寒条件极易冰冻。文章模拟西藏地区气候地理特征,利用电伴热和包裹不同保温材质作为保温防冻措施,以水作为储热介质,研究不同功率电伴热带和保温材质对取水装置保温性能的影响。分析了不同保温材质下储热介质的平均升温速率、降温速率,并对比了其经济性。结果表明:2×25 mm橡塑保温棉辅以40 W/m电伴热带的保温效果最佳,可保证冬季严寒条件下取水装置保持不冻,并且该材料经济性较好,在工程应用中具有广泛前景。

Comparison of the anti-apoptotic effects of 15-and 35-minute suspended moxibustion after focal cerebral ischemia/reperfusion injury

Heat-sensitive suspended moxibustion has a neuroprotective effect against focal cerebral ischemia/reperfusion injury, but the underly- ing mechanisms remain unclear. The duration of heat-sensitive suspended moxibustion （usually from 30 minutes to 1 hour） is longer than traditional suspended moxibustion （usually 15 minutes）. However, the effects of 15- and 35-minute suspended moxibustion in rats with cerebra/ischemia/reperfusion injury are poorly understood. In this study, we performed 15- or 35-minute suspended moxibustion at acupoint Dazhui （GV14） in an adult rat model of focal cerebral ischemia/reperfusion injury. Infarct volume was evaluated with the 2,3,5-triphenyltetrazolium chloride assay. Histopathological changes and neuronal apoptosis at the injury site were assessed by hematoxy- lin-eosin staining and terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Caspase-9 and caspase-3 expression at the in- jury site was detected using immunofluorescent staining. Bax and Bcl-2 expression at the injury site was assessed using western blot assay. In the 35-minute moxibustion group, infarct volume was decreased, neuronal apoptosis was reduced, caspase-9, caspase-3 and Bax expres- sion was lower, and Bcl-2 expression was increased, compared with the 15-minute moxibustion group. Our findings show that 35-minute moxibustion has a greater anti-apoptotic effect than 15-minute moxibustion after focal cerebral ischemia/reperfusion injury.