基于距离度量学习的半监督多视角谱聚类算法

为了有效利用少量先验信息提高多视角数据聚类效果,提出了一种基于距离度量学习的半监督多视角谱聚类算法(简称ML-SMC)。首先,利用距离度量学习引入先验信息,将多视角数据映射到反映先验约束条件的空间.然后,根据相似性构造每个视角的视图,将多视角聚类问题转化为最小正则割的图划分问题。实验结果表明：ML-SMC算法聚类结果的精度优于3种经典的多视角聚类算法和4种半监督单视角聚类算法。并且通过利用少量先验信息ML-SMC算法能够有效提高聚类效果。     

Differential Domain Distribution of gnomAD- and Disease-Linked Connexin Missense Variants

Twenty-one human genes encode connexins, a family of homologous proteins making gap junction (GJ) channels, which mediate direct intercellular communication to synchronize tissue/organ activities. Genetic variants in more than half of the connexin genes are associated with dozens of different Mendelian inherited diseases. With rapid advances in DNA sequencing technology, more variants are being identified not only in families and individuals with diseases but also in people in the general population without any apparent linkage to Mendelian inherited diseases. Nevertheless, it remains challenging to classify the pathogenicity of a newly identified connexin variant. Here, we analyzed the disease- and Genome Aggregation Database (gnomAD, as a proxy of the general population)-linked variants in the coding region of the four disease-linked α connexin genes. We found that the most abundant and position-sensitive missense variants showed distinct domain distribution preference between disease- and gnomAD-linked variants. Plotting missense variants on topological and structural models revealed that disease-linked missense variants are highly enriched on the structurally stable/resolved domains, especially the pore-lining domains, while the gnomAD-linked missense variants are highly enriched in the structurally unstable/unresolved domains, especially the carboxyl terminus. In addition, disease-linked variants tend to be on highly conserved residues and those positions show evolutionary co-variation, while the gnomAD-linked missense variants are likely on less conserved residue positions and on positions without co-variation. Collectively, the revealed distribution patterns of disease- and gnomAD-linked missense variants further our understanding of the GJ structure–biological function relationship, which is valuable for classifying the pathogenicity of newly identified connexin variants.     

Dual Activity BLEG-1 from Bacillus lehensis G1 Revealed Structural Resemblance to B3 Metallo-β-Lactamase and Glyoxalase II: An Insight into Its Enzyme Promiscuity and Evolutionary Divergence

Metallo-β-lactamases (MBLs) are class B β-lactamases from the metallo-hydrolase-like MBL-fold superfamily which act on a broad range of β-lactam antibiotics. A previous study on BLEG-1 (formerly called Bleg1_2437), a hypothetical protein from Bacillus lehensis G1, revealed sequence similarity and activity to B3 subclass MBLs, despite its evolutionary divergence from these enzymes. Its relatedness to glyoxalase II (GLXII) raises the possibility of its enzymatic promiscuity and unique structural features compared to other MBLs and GLXIIs. This present study highlights that BLEG-1 possessed both MBL and GLXII activities with similar catalytic efficiencies. Its crystal structure revealed highly similar active site configuration to YcbL and GloB GLXIIs from Salmonella enterica, and L1 B3 MBL from Stenotrophomonas maltophilia. However, different from GLXIIs, BLEG-1 has an insertion of an active-site loop, forming a binding cavity similar to B3 MBL at the N-terminal region. We propose that BLEG-1 could possibly have evolved from GLXII and adopted MBL activity through this insertion.     

NMR-Guided Repositioning of Non-Steroidal Anti-Inflammatory Drugs into Tight Junction Modulators

Bioavailability is a major bottleneck in the clinical application of medium molecular weight therapeutics, including protein and peptide drugs. Paracellular transport of these molecules is hampered by intercellular tight junction (TJ) complexes. Therefore, safe chemical regulators for TJ loosening are desired. Here, we showed a potential application of select non-steroidal anti-inflammatory drugs (NSAIDs) as TJ modulators. Based on our previous observation that diclofenac and flufenamic acid directly bound various PDZ domains with a broad specificity, we applied solution nuclear magnetic resonance techniques to examine the interaction of other NSAIDs and the first PDZ domain (PDZ1) of zonula occludens (ZO)-1, ZO-1(PDZ1). Inhibition of ZO-1(PDZ1) is expected to provide loosening of the epithelial barrier function because the domain plays a crucial role in maintaining TJ integrity. Accordingly, diclofenac and indomethacin were found to decrease the subcellular localization of claudin (CLD)-2 but not occludin and ZO-1 at the apicolateral intercellular compartment of Madin–Darby canine kidney (MDCK) II cells. These NSAIDs exhibited 125–155% improved paracellular efflux of fluorescein isothiocyanate insulin for the Caco-2 cell monolayer. We propose that these NSAIDs can be repurposed as drug absorption enhancers for peptide drugs.     

A Holistic Evolutionary and 3D Pharmacophore Modelling Study Provides Insights into the Metabolism,Function, and Substrate Selectivity of the Human Monocarboxylate Transporter 4 (hMCT4)

Monocarboxylate transporters (MCTs) are of great research interest for their role in cancer cell metabolism and their potential ability to transport pharmacologically relevant compounds across the membrane. Each member of the MCT family could potentially provide novel therapeutic approaches to various diseases. The major differences among MCTs are related to each of their specific metabolic roles, their relative substrate and inhibitor affinities, the regulation of their expression, their intracellular localization, and their tissue distribution. MCT4 is the main mediator for the efflux of L-lactate produced in the cell. Thus, MCT4 maintains the glycolytic phenotype of the cancer cell by supplying the molecular resources for tumor cell proliferation and promotes the acidification of the extracellular microenvironment from the co-transport of protons. A promising therapeutic strategy in anti-cancer drug design is the selective inhibition of MCT4 for the glycolytic suppression of solid tumors. A small number of studies indicate molecules for dual inhibition of MCT1 and MCT4; however, no selective inhibitor with high-affinity for MCT4 has been identified. In this study, we attempt to approach the structural characteristics of MCT4 through an in silico pipeline for molecular modelling and pharmacophore elucidation towards the identification of specific inhibitors as a novel anti-cancer strategy.     

混合进化算法研究甲基叔戊基醚合成反应动力学

将遗传算法与模拟退火算法相结合,以自适应多重退火交叉策略和自适应多重退火变异策略分别代替传统遗传算法中的单一交叉策略和单一变异策略,在此基础上进一步与进化策略相结合,开发出了一种多进化模式的混合进化算法. 用以上算法对以强酸性阳离子交换树脂A-15为催化剂用甲醇和叔戊醇为原料合成甲基叔戊基醚反应动力学方程中的速度常数、水的阻害系数等参数进行了求解计算,并与传统算法进行了比较. 结果表明：本研究所提出的混合进化算法收敛速度快,估算精度高,有效抑制了早熟现象的发生,所得到的有关动力学参数可靠,模型计算结果与实验结果吻合良好.     

基于聚类选择k近邻的LLE算法及故障检测

针对化工过程在多种运行模式下多种流形结构具有不同最优近邻数问题,提出了基于聚类选择k近邻的局部线性嵌入(LLE)过程监控方法。使用LLE算法提取高维数据的低维子流形,通过局部线性回归得到高维数据空间到特征空间的映射矩阵;选择Silhouette指标作为聚类有效性指标评估嵌入空间样本信息的相似性,进而确定最优近邻数,根据映射矩阵构建故障监控统计量及其控制限,进行故障检测。最后将所提算法与其他经典算法应用于TE化工过程对比分析,验证了算法的有效性。     

Lipids from Wastewater-Activated Sludge Cultivated on Acetic Acid as Potential Alternatives to High-Value Oils and Fats

This study focuses on new interpretations of the published literature by statistically evaluating the potential of microbial lipids from activated sludge (AS) as alternatives to high-value oils and fats. There are two data analysis stages involved in this study after compilation and organization of fatty acid profiles from the literature databases: (1) comparison of fatty acid profiles of the cultivated AS lipids with that of oils and fats found in the literature databases, and (2) hierarchical cluster analysis of the fatty acids of the combined dataset of literature oils and fats, and the AS lipids. Results show that fatty acid profiles of lipids from cultivated AS were similar to the fatty acid profiles of some oils and fats of plant, animal, single-microbial cultures, and algal origins; hence, lipids from AS could be potential alternatives to specialty oils and fats. The cultivation conditions of AS during lipid content enhancement may influence lipid application.     

A novel interactive preferential evolutionary method for controller tuning in chemical processes☆

In response to many multi-attribute decision-making (MADM) problems involved in chemical processes such as controller tuning, which suffer human's subjective preferential nature in human–computer inter...     

An iterative two‐step sequential phase partition (ITSPP) method for batch process modeling and online monitoring

Operating at different manufacturing steps, multiphase modeling and analysis of the batch process are advantageous to improving monitoring performance and understanding manufacturing processes. Although many phase partition algorithms have been proposed, they have some disadvantages and cause problems: (1) time sequence disorder, which requires elaborate post‐treatments; (2) a lack of quantitative index to indicate transition patterns; and (3) tunable parameters that cannot be quantitatively determined. To effectively overcome these problems, an iterative two‐step sequential phase partition algorithm is proposed in the present work. In the first step, initial phase partition results are obtained by checking changes of the control limit of squared prediction error. Sequentially, the fast search and find of density peaks clustering algorithm is employed to adjust the degradation degree and update the phase partition results. These two steps are iteratively executed until a proper degradation degree is found for the first phase. Then, the remaining phases are processed one by one using the same procedure. Moreover, a statistical index is quantitatively defined based on density and distance analysis to judge whether a process has transitions, and when the transition regions begin and end. In this way, the phases and transition patterns are quantitatively determined without ambiguity from the perspective of monitoring performance. The effectiveness of the proposed method is illustrated by a numerical example and a typical industrial case. Several typical phase partition algorithms are also employed for comprehensive comparisons with the proposed method. © 2016 American Institute of Chemical Engineers AIChE J, 62: 2358–2373, 2016