CBP/P300溴结构域联芳基类抑制剂三维定量构效关系研究

CREB结合蛋白(CBP)和与其高度同源的P300蛋白是组蛋白乙酰化酶的两个亚型,两者通过它们的溴结构域(bromodomain,BRD)与染色质结合,目前,CBP/P300已经成为人类在肿瘤靶点领域中的研究热点。本研究基于CBP/P300溴结构域联芳基类抑制剂建立三维定量构效关系,采用比较分子力场分析法(Co MFA)和比较分子相似性指数分析法(Co MSIA)分别建立35个已知活性抑制剂的3D-QSAR模型,以确定CBP/P300溴结构域联芳基类抑制剂分子结构与生物活性之间的定量关系。Co MFA和Co MSIA模型活性数据p IC50的预测值与实验值基本一致,说明这两个模型具有较高的预测能力和统计学意义。根据Co MFA和Co MSIA模型所提供的立体场、静电场、疏水场、氢键给体场、氢键供体场等信息提出了改善此类抑制剂活性的药物设计思路,为指导设计具有更高活性的新分子和预测更加有效的CBP/P300溴结构域抑制剂提供理论依据。     

基于Copula-SV-t模型的沪深300期现相关性分析

结合SV-t模型和Copula模型,建立两变量金融时间序列的Copula-SV-t模型,并以刚刚上市交易的我国沪深300期货市场和其现货指数为例利用建立的模型进行相关程度和相关模式的分析,根据采用不同的Archimedean Copula函数,通过平方欧式距离评价Copula函数的拟合度.结果表明,股指期现市场之间存在条件正相关关系,且存在非对称的尾部相关关系,上尾部的相关性要强于下尾部的相关性,即期货市场的助涨效应要强于助跌效应.     

Numerical investigation on radiation characteristics of discrete-frequency noise from scarf and scoop aero-intakes

Numerical studies have been carried out to investigate the detailed geometrical effects of full three-dimensional aero-intakes on the radiation of the discrete-frequency rotor-stator interaction noise. The near-field acoustic radiation characteristics and the far-field directivity patterns from the scarf and scoop aero-intakes with three different scarf/scoop angles are quantitatively analyzed and compared. The near-field predictions were obtained by solving the linearized Euler equations with computational aeroacoustic techniques consisting of high-order finite difference scheme, non-reflecting boundary conditions, overset grids and parallel computational methods. For the prediction of far-field directivity pattern, the Kirchhoff integral method was applied. By comparing the directivities of discrete-frequency noise radiating from the scarf and the scoop aero-intakes with that from an axisymmetric aero-intake, it is shown that the 7 dB noise reduction at downward peak radiation angle can be achieved by using the scoop aero-intake with scoop angle of 15°, and the 5 dB noise reduction by the scarf aero-intake with the scarf angle of 15°. The scattering of the radiating acoustic wave by the background mean flow around the aero-intakes shifts the peak lobe radiation angle toward ground and increases the amplitude of the acoustic pressure compared with the cases without mean flow effect. Overall, the scoop aero-intake was found to be more effective than the scarf and the axisymmetric aero-intakes in view of the lower noise radiation toward ground.     

Failure to direct detect magnetic field dephasing corresponding to ERP generation

Functional magnetic resonance imaging (fMRI) has become the method of choice for mapping brain activity in human subjects and detects changes in regional blood oxygenation and volume associated with local changes in neuronal activity. While imaging based on blood oxygenation level dependent (BOLD) contrast has good spatial resolution and sensitivity, the hemodynamic signal develops relatively slowly and is only indirectly related to neuronal activity. An alternative approach termed magnetic source magnetic resonance imaging (msMRI) is based on the premise that neural activity may be mapped by magnetic resonance imaging (MRI) with greater temporal resolution by detecting the local magnetic field perturbations associated with local neuronal electric currents. We used a hybrid ms/BOLD MRI method to investigate whether msMRI could detect signal changes that occur simultaneously at the time of the production of well-defined event-related potentials, the P300 and N170, in regions that previously have been identified as generators of these electrical signals. Robust BOLD activations occurred after some seconds, but we were unable to detect any significant changes in the T2*-weighted signal in these locations that correlated temporally with the timings of the evoked response potentials (ERPs).     

Effects of ultrasound treatment on muscle structure,volatile compounds,and small molecule metabolites of salted Culter alburnus fish

This study investigated the effects of ultrasound treatment on the quality of salted Culter alburnus fish. The results showed that with the increasing ultrasound power, the structural degradation of muscle fibers was intensified, and the conformation of myofibrillar protein was significantly changed. The high-power ultrasound treatment group (300 W) had relatively higher thiobarbiturate reactive substance content (0.37 mg malondialdehyde eq/kg) and peroxidation value (0.63 mmol/kg). A total of 66 volatile compounds were identified with obvious differences among groups. The 200 W ultrasound group exhibited fewer fishy substances (Hexanal, 1-Pentene-3-ol, and 1-Octane-3-ol). Compared with control group, ultrasound groups (200, 300 W) contained more umami taste-related amino peptides such as γ-Glu-Met, γ-Glu-Ala, and Asn-pro. In the ultrasound treatment group, L-isoleucine and L-methionine, which may be used as flavor precursors, were significantly down-regulated, while carbohydrates and its metabolites were up-regulated. Amino acid, carbohydrate, and FA (fatty acyls) metabolism products in salted fish were enriched by ultrasound treatment, and those products might ultimately be related to the taste and flavor of salted fish.