项目驱动式教学法在计算机基础课程中的应用

项目驱动式教学做为一种新兴的教学模式越来越多的应用于各门学科的教学应用当中。计算机基础这门课程由于其理论知识更新速度快,实践操作要求高的特点,将之与项目驱动式教学法相结合可以起到很好的教学效果。本文将传统教学方法和项目驱动式教学法进行对比,针对当前教学过程中存在的问题提出相应的解决方法。     

一种基于UML状态图的规约变异测试方法

规约变异测试从软件功能的角度,对规约进行分析,从而揭示规约中存在的问题。本文提出一种基于UML状态图的变异测试方法,针对每种变异算子,分析其是否会引入冲突,进而有效避免不合理的变异操作;分析了每种变异算子产生等价变异体的条件,能够在生成变异体的同时检测并移除等价变异体,进而减少其对测试过程的影响;给出了杀掉每种变异体所需满足的条件,可在此基础上产生杀掉特定变异体所需的测试用例,从而提高测试用例集的质量。在此基础上,根据变异算子的实际功能,整合了功能相同的算子,减少了变异算子的数量,从而进一步降低了变异测试的开销。实验结果表明,本方法能够较好地提高测试用例的质量,进而提升测试的效率。     

基于机会约束的电动汽车充光储一体化充电站容量优化方法

针对电动汽车充电站建设运营成本高,土地利用率较低,功能单一的缺点,提出了电动汽车充光储一体化充电站的容量优化方法。考虑光伏出力及电动汽车充电负荷的不确定性,研究在不确定性环境下的容量配置问题,以保证优化方案的可靠性。基于机会约束规划,以建设运营成本最小为目标建立电动汽车充光储一体化充电站容量配置模型,通过序列运算理论将模型中含有随机变量的约束进行确定性转化,采用CPLEX作为模型的求解工具。算例验证了所提模型及方法的有效性。     

基于柔性互联技术的含高渗透率新能源配电网多目标优化运行

智能软开关（SOP）可控制潮流、提供无功补偿,进而改善配电网电压、降低网损。因此,针对可再生能源大规模接入配电网后电能质量下降问题,采用K-means算法构建风-光典型场景,同时建立了基于SOP、可投切电容器的含高渗透率分布式电源的主动配电网优化运行模型。该模型以电压偏差、系统网损最小以及系统运行成本最低为目标,综合考虑了能源利用率及系统运行稳定性。最后利用基于参考点的非支配排序方法的多目标优化算法（NSGA-III）进行求解,输出Pareto最优解集,并采用改进的IEEE 33节点系统对所建立模型的有效性进行了验证。     

计及多能需求的综合能源服务商优化运行策略研究

随着分布式发电技术的不断成熟及发展,未来综合能源服务将是整合不同类型分布式发电并满足用户不同用能需求的有效途径。提出了一种含有多种分布式发电资源同时考虑多用能需求的综合能源服务商优化运行策略模型。首先建立了含有风电、光伏、燃气轮机、电储能、电热泵、辅助锅炉等分布式资源及电、热用能需求的园区综合能源系统优化调度模型;其次计算优化运行后的能源利用效率;最后,分析对比了不同季节、实时电价及天然气价格变化对综合能源服务商运行策略及盈利的影响。仿真结果验证了模型的有效性,其中综合能源服务商的收益对天然气的价格变化更为敏感。     

基于改进深度强化学习的智能微电网群控制优化方法

针对微电网群控制的经济效益、负荷波动以及碳排放问题,提出一种基于改进深度强化学习的智能微电网群运行优化方法。首先,计及分布式电源、电动汽车及负荷特性,提出微电网的系统模型。然后,针对微电网群的运行特点,提出4个系统优化目标和5个约束条件,并且引入分时电价机制调控负荷运行。最后,利用改进深度强化学习算法对微电网群进行优化,合理调控多种能源协同出力,调整负荷状态,实现电网经济运行。仿真结果表明了所提方法的有效性,与其他方法相比,其收益较高且碳排放量较小,可实现系统的经济环保运行。     

张北柔性直流电网交流耗能装置运行特性仿真

为验证利用可控硅将大功率电阻快速投入交流系统的耗能装置能否在投运后安全可靠运行,从而解决张北柔直工程双极性接线故障状况下过负荷造成的线路和设备损毁问题,该工作通过PSCAD电磁暂态仿真软件建立了张北换流站交流耗能装置的电路模型;然后对耗能装置的运行特性进行了分析,并模拟了过剩风能与耗能装置分组投切时系统的电压电流;最后讨论了耗能装置故障状况对系统的影响。结果表明:耗能装置可以快速有效地消纳过剩功率,且当其故障时不会对系统造成威胁。可见交流耗能装置设计合理,可将其投运在柔性直流系统中。     

Rational Design of CYP3A4 Inhibitors: A One-Atom Linker Elongation in Ritonavir-Like Compounds Leads to a Marked Improvement in the Binding Strength

Inhibition of the major human drug-metabolizing cytochrome P450 3A4 (CYP3A4) by pharmaceuticals and other xenobiotics could lead to toxicity, drug–drug interactions and other adverse effects, as well as pharmacoenhancement. Despite serious clinical implications, the structural basis and attributes required for the potent inhibition of CYP3A4 remain to be established. We utilized a rational inhibitor design to investigate the structure–activity relationships in the analogues of ritonavir, the most potent CYP3A4 inhibitor in clinical use. This study elucidated the optimal length of the head-group spacer using eleven (series V) analogues with the R₁/R₂ side-groups as phenyls or R₁–phenyl/R₂–indole/naphthalene in various stereo configurations. Spectral, functional and structural characterization of the inhibitory complexes showed that a one-atom head-group linker elongation, from pyridyl–ethyl to pyridyl–propyl, was beneficial and markedly improved K_s, IC₅₀ and thermostability of CYP3A4. In contrast, a two-atom linker extension led to a multi-fold decrease in the binding and inhibitory strength, possibly due to spatial and/or conformational constraints. The lead compound, 3h, was among the best inhibitors designed so far and overall, the strongest binder (K_s and IC₅₀ of 0.007 and 0.090 µM, respectively). 3h was the fourth structurally simpler inhibitor superior to ritonavir, which further demonstrates the power of our approach.     

The GAUGAA Motif Is Responsible for the Binding between circSMARCA5 and SRSF1 and Related Downstream Effects on Glioblastoma Multiforme Cell Migration and Angiogenic Potential

Circular RNAs (circRNAs) are a large class of RNAs with regulatory functions within cells. We recently showed that circSMARCA5 is a tumor suppressor in glioblastoma multiforme (GBM) and acts as a decoy for Serine and Arginine Rich Splicing Factor 1 (SRSF1) through six predicted binding sites (BSs). Here we characterized RNA motifs functionally involved in the interaction between circSMARCA5 and SRSF1. Three different circSMARCA5 molecules (Mut1, Mut2, Mut3), each mutated in two predicted SRSF1 BSs at once, were obtained through PCR-based replacement of wild-type (WT) BS sequences and cloned in three independent pcDNA3 vectors. Mut1 significantly decreased its capability to interact with SRSF1 as compared to WT, based on the RNA immunoprecipitation assay. In silico analysis through the “Find Individual Motif Occurrences” (FIMO) algorithm showed GAUGAA as an experimentally validated SRSF1 binding motif significantly overrepresented within both predicted SRSF1 BSs mutated in Mut1 (q-value = 0.0011). U87MG and CAS-1, transfected with Mut1, significantly increased their migration with respect to controls transfected with WT, as revealed by the cell exclusion zone assay. Immortalized human brain microvascular endothelial cells (IM-HBMEC) exposed to conditioned medium (CM) harvested from U87MG and CAS-1 transfected with Mut1 significantly sprouted more than those treated with CM harvested from U87MG and CAS-1 transfected with WT, as shown by the tube formation assay. qRT-PCR showed that the intracellular pro- to anti-angiogenic Vascular Endothelial Growth Factor A (VEGFA) mRNA isoform ratio and the amount of total VEGFA mRNA secreted in CM significantly increased in Mut1-transfected CAS-1 as compared to controls transfected with WT. Our data suggest that GAUGAA is the RNA motif responsible for the interaction between circSMARCA5 and SRSF1 as well as for the circSMARCA5-mediated control of GBM cell migration and angiogenic potential.     

The GNAQ T96S Mutation Affects Cell Signaling and Enhances the Oncogenic Properties of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC), the most common malignant tumor in the liver, grows and metastasizes rapidly. Despite advances in treatment modalities, the five-year survival rate of HCC remains less than 30%. We sought genetic mutations that may affect the oncogenic properties of HCC, using The Cancer Genome Atlas (TCGA) data analysis. We found that the GNAQ T96S mutation (threonine 96 to serine alteration of the Gαq protein) was present in 12 out of 373 HCC patients (3.2%). To examine the effect of the GNAQ T96S mutation on HCC, we transfected the SK-Hep-1 cell line with the wild-type or the mutant GNAQ T96S expression vector. Transfection with the wild-type GNAQ expression vector enhanced anchorage-independent growth, migration, and the MAPK pathways in the SK-Hep-1 cells compared to control vector transfection. Moreover, cell proliferation, anchorage-independent growth, migration, and the MAPK pathways were further enhanced in the SK-Hep-1 cells transfected with the GNAQ T96S expression vector compared to the wild-type GNAQ-transfected cells. In silico structural analysis shows that the substitution of the GNAQ amino acid threonine 96 with a serine may destabilize the interaction between the regulator of G protein signaling (RGS) protein and GNAQ. This may reduce the inhibitory effect of RGS on GNAQ signaling, enhancing the GNAQ signaling pathway. Single nucleotide polymorphism (SNP) genotyping analysis for Korean HCC patients shows that the GNAQ T96S mutation was found in only one of the 456 patients (0.22%). Our data suggest that the GNAQ T96S hotspot mutation may play an oncogenic role in HCC by potentiating the GNAQ signal transduction pathway.