Identification of Pharmacophoric Fragments of DYRK1A Inhibitors Using Machine Learning Classification Models

Dual-specific tyrosine phosphorylation regulated kinase 1 (DYRK1A) has been regarded as a potential therapeutic target of neurodegenerative diseases, and considerable progress has been made in the discovery of DYRK1A inhibitors. Identification of pharmacophoric fragments provides valuable information for structure- and fragment-based design of potent and selective DYRK1A inhibitors. In this study, seven machine learning methods along with five molecular fingerprints were employed to develop qualitative classification models of DYRK1A inhibitors, which were evaluated by cross-validation, test set, and external validation set with four performance indicators of predictive classification accuracy (CA), the area under receiver operating characteristic (AUC), Matthews correlation coefficient (MCC), and balanced accuracy (BA). The PubChem fingerprint-support vector machine model (CA = 0.909, AUC = 0.933, MCC = 0.717, BA = 0.855) and PubChem fingerprint along with the artificial neural model (CA = 0.862, AUC = 0.911, MCC = 0.705, BA = 0.870) were considered as the optimal modes for training set and test set, respectively. A hybrid data balancing method SMOTETL, a combination of synthetic minority over-sampling technique (SMOTE) and Tomek link (TL) algorithms, was applied to explore the impact of balanced learning on the performance of models. Based on the frequency analysis and information gain, pharmacophoric fragments related to DYRK1A inhibition were also identified. All the results will provide theoretical supports and clues for the screening and design of novel DYRK1A inhibitors.     

双层PLS算法及其在近红外光谱分析中的应用

针对近红外光谱数据局部效应显著,变量个数多,且彼此间常存在严重的复共线性,并与样品组分含量呈非线性关系,构建了一种双层非线性偏最小二乘回归 (DNPLSR)算法。它将非线性回归和偏最小二 乘(PLS)相结合,先在外层由PLS从样本数据中提取成分,并实现每对成分间的非线性映射,再在内层实施PLS算法,将外层因变量成分的拟合误差反馈计算转换权向量的增量,进一步修正转换权向量,以使外层所提取的成分对因变量具有更优的解释能力。最后,将该法应用于80个谷物样品的水组分含量与其近红外光谱的定量关系建模,效果良好,显示出很强的学习能力,所建模型的预报性能也优于其他方法。     

Fourier algorithm method for reconstruction of large-aperture digital holograms based on phase compensation

To simplify the reconstruction calculation of a large-aperture digital hologram we propose a novel Fourier-transformation reconstruction algorithm. When the reconstructed wave is the same as or similar to the reference wave, the higher-order phase term of reconstruction can be compensated for. For example, the variation between the higher-order phase term and the aperture angle with a different field of view in in-line phase-shifting digital holography is analyzed.     

二维衰减全反射红外光谱研究水在聚酰亚胺/二氧化硅纳米高分子复合膜中的吸附扩散行为

考虑到基于聚酰亚胺衍生物的电子器件的稳定性和性能,运用二维衰减全反射红外相关光潜研究了水在聚酰亚胺衍生物:poly(4’4- oxydiphenylene pyromellitimide)和二氧化硅的纳米高分子复合膜中的动态吸附和扩散行为．二维相关光谱区分出了三种不同氢键强度的水分子状态,同时,氢键的数量和强度还对不同状态水分子的扩散速率起了决定性的作用,和PI聚合物本身以及PI表面残留的硅酸形成氢键的水分子的扩散速度则最慢.     

Effect of Mn-site vacancies on the magnetic entropy change and the Curie temperature of La0.67Ca0.33Mn1−xO3 perovskite

Single-phase polycrystalline samples of La_0.67Ca_0.33Mn_1−xO₃ (x=0.00, 0.02, 0.04, 0.06) have been prepared using the sol-gel method. The structure, magnetocaloric properties and the Curie temperature of the samples with different Mn vacancy concentrations have been investigated. The experimental results show that vacancy doping at the Mn-sites has a significant influence on the magnetic properties of La_0.67Ca_0.33Mn_1−xO₃. The Curie temperature decreases monotonically with increasing the Mn-site vacancy concentration x. A remarkable enhancement of the magnetic entropy change has been obtained in the La_0.67Ca_0.33Mn_0.98O₃ sample. The entropy change reaches |ΔS_M|=3.10 J kg⁻¹ K⁻¹ at its Curie temperature (264 K) under an applied magnetic field H=10 kOe, which is almost the same value as that of pure Gd.     

Development and investigation of an optical tilt sensor

An optical tilt sensor was developed and its performance was investigated. The tilt sensor set-up consisted of a laser light source, lenses and an image sensor. A precision reference tilt sensor was also installed on the same stage, and the measurement results of tilt angles using the optical and reference tilt sensors were correlated. The correlation coefficient (R-value) obtained under ideal conditions was 0.99454, indicating that the optical tilt sensor could produce as accurate measurements as the precision reference tilt sensor. The R-value decreased to 0.97714 and 0.93209 when the image sensor was shifted backwards and forwards from the focal plane by 1 mm, respectively. The R-value decreased to 0.96840 when the tilt sensor was performed with the room light turned on. There were not significant differences in the measurement results obtained with air conditioners turned on and off, indicating that the optical tilt sensor was robust and was not sensitive to the surrounding air turbulence. These findings are useful for the final design of the optical tilt sensor.     

Influence of Co–Zr substitution on coercivity in Ba ferrites

Polycrystalline BaCo_xZr_xFe_11.5−2xO_18.25 samples with 0?x?0.6$0?x?0.6$ ions per formula units were prepared by modified citrate precursor method with the initial ratio of Ba:Fe equal to 1:11.5. The cationic site preferences of Co²⁺ and Zr⁴⁺ in Co–Zr substituted Ba ferrite were investigated by magnetic measurements and X-ray diffractometer (XRD) analysis. The coercivity H_c was decreasing with increasing Co–Zr substitution. The datum showed that the max coercive force (H_c) was obtained when substitution of 0.2, while the best saturation magnetizations (M_s) was obtained when substitution of 0.4.     

纳米ZnO／石蜡复合相变材料的热物理性质研究

本文通过将纳米氧化锌（ZnO）颗粒加入熔融的石蜡（PW）并进行搅拌和超声制备了一种纳米ZnO／PW复合相变储能材料。为使纳米氧化锌在基体物质中分散均匀,在制备过程中使用了搅拌和超声以制备均匀的复合材料。使用扫描电镜观察其微观结构表明氧化锌在石蜡中分散良好。对所得ZnO／PW复合相变材料的相变温度、相变焓及导热系数等热物...     

基于ANSYS的芯片冷却器传热分析

针对微槽式芯片冷却器,建立三维仿真模型,分析其稳态工况下的传热情况,获得其温度和热应力分布.分析了五种不同结构形式芯片冷却器工作性能的影响,比较了纯铜和氮化硅复合物两种材质对散热性能的影响.结果表明,铜质冷却器散热性能较好,但内部热应力却高于复合材质冷却器.通过将原冷却通道分割成两个相同的小通道,可提高冷却性能,且应将...     

次谐波聚束器相位控制的算法改进

 为实现次谐波聚束器的数字化相位控制,利用下变频、IQ调制解调技术及商业化的PXI系统,开发了以LabVIEW为平台的低电平控制器。控制器采用了具有自学习和自适应能力的单神经元自适应PID的控制算法,满足了相位稳定度的要求,通过现场测试与传统PID算法进行比较,验证了该算法稳定性好、响应快、抗干扰能力强。