中国能源资源开发利用布局与国土资源节约集约耦合关系

本文主要以我国东部、东北部、中部和西部为研究对象,从能源资源潜力、能源勘探开发现状、能源资源开发利用布局等方面,探究能源资源开发利用和国土资源节约集约之间的耦合关系,并提出相关建议,这将对我国走结构优化、节约集约、效率提升的绿色发展新路具有一定的参考价值。     

奥利维蒂展厅的猜想（下篇）：形式背后的思考

本文选取奥利维蒂展厅（Negozio Olivetti）夹层廊桥为研究对象。以之最终建造结果为出发点层层还原形式背后的思考,涉及结构、空间体验、场地应答、建造逻辑等层面。并最终揭示斯卡帕语言的精确性,以及其形式推敲的方法。     

Structural Basis of Cysteine Ligase MshC Inhibition by Cysteinyl-Sulfonamides

Mycothiol (MSH), the major cellular thiol in Mycobacterium tuberculosis (Mtb), plays an essential role in the resistance of Mtb to various antibiotics and oxidative stresses. MshC catalyzes the ATP-dependent ligation of 1-O-(2-amino-2-deoxy-α-d-glucopyranosyl)-d-myo-inositol (GlcN-Ins) with l-cysteine (l-Cys) to form l-Cys-GlcN-Ins, the penultimate step in MSH biosynthesis. The inhibition of MshC is lethal to Mtb. In the present study, five new cysteinyl-sulfonamides were synthesized, and their binding affinity with MshC was evaluated using a thermal shift assay. Two of them bind the target with EC₅₀ values of 219 and 231 µM. Crystal structures of full-length MshC in complex with these two compounds showed that they were bound in the catalytic site of MshC, inducing dramatic conformational changes of the catalytic site compared to the apo form. In particular, the observed closure of the KMSKS loop was not detected in the published cysteinyl-sulfamoyl adenosine-bound structure, the latter likely due to trypsin treatment. Despite the confirmed binding to MshC, the compounds did not suppress Mtb culture growth, which might be explained by the lack of adequate cellular uptake. Taken together, these novel cysteinyl-sulfonamide MshC inhibitors and newly reported full-length apo and ligand-bound MshC structures provide a promising starting point for the further development of novel anti-tubercular drugs targeting MshC.     

Discovery of Flavonoids as Novel Inhibitors of ATP Citrate Lyase: Structure–Activity Relationship and Inhibition Profiles

ATP citrate lyase (ACLY) is a key enzyme in glucolipid metabolism and its aberrantly high expression is closely associated with various cancers, hyperlipemia and atherosclerotic cardiovascular diseases. Prospects of ACLY inhibitors as treatments of these diseases are excellent. To date, flavonoids have not been extensively reported as ACLY inhibitors. In our study, 138 flavonoids were screened and 21 of them were subjected to concentration–response curves. A remarkable structure–activity relationship (SAR) trend was found: ortho-dihydroxyphenyl and a conjugated system maintained by a pyrone ring were critical for inhibitory activity. Among these flavonoids, herbacetin had a typical structure and showed a non–aggregated state in solution and a high inhibition potency (IC₅₀ = 0.50 ± 0.08 μM), and therefore was selected as a representative for the ligand–protein interaction study. In thermal shift assays, herbacetin improved the thermal stability of ACLY, suggesting a direct interaction with ACLY. Kinetic studies determined that herbacetin was a noncompetitive inhibitor of ACLY, as illustrated by molecular docking and dynamics simulation. Together, this work demonstrated flavonoids as novel and potent ACLY inhibitors with a remarkable SAR trend, which may help design high–potency ACLY inhibitors. In–depth studies of herbacetin deepened our understanding of the interactions between flavonoids and ACLY.     

供电企业实施客户关系管理的难点及对策研究

本文在阐明供电企业实施客户关系管理的现实意义基础上,系统分析了供电企业实施客户关系管理存在的几大障碍因素,并提出相对的解决措施.     

鬼臼脂素衍生物的结构表征和抗肿瘤活性预测

应用分子电性距离矢量(MEDV)对鬼臼脂素衍生物进行结构表征和抗肿瘤活性的活性预测,通过逐步回归(SMR)方法建立了MEDV与活性之间的定量模型,取得了良好的结果,其模型相关系数为R=0．949;继以留一法(Leave-one—out,LOO)进行交互检验,复相关系数为R^2=0．619,说明定量相关模型具有良好的稳定性和预测能力。     

基于多重依赖关系的传递闭包研究及应用

文中通过改进Warshall-Folyd的算法,提出了一种依赖传递闭包算法和相应的动态闭包算法,其核心思想是依据依赖关系的分类和性质,定义关系矩阵和运算算子,使算法能解决选择依赖关系,并能表达直接、间接和选择三种依赖关系;同时,所提出动态算法能够运行时根据问题规模动态添加关系元素和依赖关系,解决在基本关系原则和部分关系集上求取闭包的问题。结合安全通用标准CC中关于组件间依赖关系的规定,给出了本文所提出算法的一个实际应用,表明算法取得了很好的效果。     

融合常用语的大规模疾病术语图谱构建

国家卫计委要求医疗机构使用国际疾病分类(international classification of diseases, ICD)编码,然而由于临床疾病描述存在大量的常用词,导致电子病历中录入的诊断名称与ICD编码直接映射匹配率低.基于区域健康平台上的真实诊断数据,构建了融合常用语的疾病术语图谱.具体来说,在基于疾病构成成分的规则算法基础上,提出了基于数据增强的BERT(bidirectional encoder representation from transformers)上下位关系识别算法,将5万多个诊断常用语和ICD10(international classification of diseases 10th revision,Chinese version)中的疾病进行同义关系和上下位关系识别,进一步融合了ICD11(international classification of diseases 11th revision,Chinese version)的层次结构,此外,还提出了基于疾病-科室关联图谱的任务分配方法以进行人工校验,最终94 478个疾病实体形成了包含1 460条同义关系、46 508条上下位关系的大规模疾病术语图谱.评估实验表明,基于疾病术语图谱,对临床诊断数据的覆盖率比基于ICD10的直接映射编码的覆盖率提升了75.31%,另外,利用疾病术语图谱自动进行编码疾病相比于医生人工编码会缩短约59.75%的编码时间,且正确率达到85%.
     

论《追风筝的人》中的背叛与救赎

用文学批评的手法从社会学的角度研究了卡勒德·胡赛尼的作品《追风筝的人》中阿富汗贫富悬殊下的社会伦理和人物冲突,以及身处不同阶级和宗教信仰里友谊与背叛之间的矛盾;并分析了文中风筝的象征意义,探讨了人性的本质与救赎。     

诱发IAF夹杂物与原晶粒的尺寸匹配关系

 对于氧化物冶金船板钢而言,细小弥散分布的夹杂物会对其原始晶粒产生钉扎和诱发晶内铁素体的双重作用,且研究发现诱发晶内铁素体的夹杂物尺寸与原始奥氏体晶粒尺寸存在一定的匹配关系。围绕上述问题进行了系统的分析研究和数据统计,结果表明,不同晶粒尺寸下,诱发晶内铁素体的夹杂物尺寸与原奥氏体晶粒度间存在近似线性关系,且随着奥氏体晶粒度的增大,诱发晶内铁素体的夹杂物尺寸则相应减小。