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Machine Learning Modeling of Protein-intrinsic Features Predicts Tractability of Targeted Protein Degradation

Genomics, Proteomics & Bioinformatics 2022年第5期20卷 882-898页

作者： wubing zhang Shourya S.Roy Burman Jiaye Chen Katherine A.Donovan Yang Cao Chelsea Shu Boning zhang Zexian Zeng Shengqing Gu Yi zhang Dian Li Eric S.Fischer Collin Tokheim X.Shirley Liu Department of Data Science Dana-Farber Cancer InstituteBostonMA 02215USA Department of Biostatistics Harvard T.H.Chan School of Public HealthBostonMA 02115USA Department of Cancer Biology Dana-Farber Cancer InstituteBostonMA 02215USA Department of Biological Chemistry and Molecular Pharmacology Harvard Medical SchoolBostonMA 02115USA Department of Biomedical Informatics Harvard Medical SchoolBostonMA 02115USA Center of Growth Metabolismand AgingKey Laboratory of Bio-resource and Eco-environmentMinistry of EducationCollege of Life SciencesSichuan UniversityChengdu 610064China Research Scholar Initiative Graduate School of Arts and SciencesHarvard UniversityCambridgeMA 02138USA

Targeted protein degradation(TPD)has rapidly emerged as a therapeutic modality to eliminate previously undruggable proteins by repurposing the cell’s endogenous protein degradation ***,the susceptibility of proteins for targeting by TPD approaches,termed“degradability”,is largely ***,we developed a machine learning model,model-free analysis of protein degradability(MAPD),to predict degradability from features intrinsic to protein *** shows accurate performance in predicting kinases that are degradable by TPD compounds[with an area under the precision–recall curve(AUPRC)of 0.759 and an area under the receiver operating characteristic curve(AUROC)of 0.775]and is likely generalizable to independent non-kinase *** found five features with statistical significance to achieve optimal prediction,with ubiquitination potential being the most *** structural modeling,we found that E2-accessible ubiquitination sites,but not lysine residues in general,are particularly associated with kinase ***,we extended MAPD predictions to the entire proteome to find964 disease-causing proteins(including proteins encoded by 278 cancer genes)that may be tractable to TPD drug development.

关键词： Targeted protein degradation Degradability Protein-intrinsic feature Ubiquitination Machine learning

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Study of full waveform inversion based on L-BFGS algorithm

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Global Geology 2012年第2期15卷 161-165页

作者： DENG wubing HAN Liguo zhang Bo HUANG Fei HAN Miao College of Geo-Exploration Science and Technology Jilin University Changchun 130026 China

Full waveform inversion size of full waveform inversion will and the limitation of full waveform is mainly used to obtain high resolution velocity models of subsurface. The lead to a gigantic computation cost. Under the available computer resource inversion, the authors propose L-BFGS algorithm as the optimization method to solve this problem. In order to demonstrate the flexibility of the method, three different numerical experi- ments have been done to analyze the properties of full waveform inversion based on L-BFGS.

关键词： L-BFGS numerical optimization acoustic wave equation initial model full waveform inversion

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解决雷达方位角突变问题的一种方法

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现代雷达 2019年第3期41卷 53-57页

作者：卓奕弘姜秋喜刘鑫刘少平张武兵国防科技大学电子对抗学院解放军77626部队

针对雷达坐标系在特定情况会发生方位角突变,造成跟踪算法发散、降低跟踪性能的问题,提出了将量测中的方位角信息转化为方位角余弦值和正弦值,并将这两个值嵌入雷达量测中,构成修正量测。由于修正量测的协方差矩阵为奇异矩阵,该文用方... 详细信息

针对雷达坐标系在特定情况会发生方位角突变,造成跟踪算法发散、降低跟踪性能的问题,提出了将量测中的方位角信息转化为方位角余弦值和正弦值,并将这两个值嵌入雷达量测中,构成修正量测。由于修正量测的协方差矩阵为奇异矩阵,该文用方位角方差构成的对角矩阵替换两个三角函数量测的协方差矩阵。仿真结果表明,修正量测及其协方差矩阵的替换对跟踪精度的影响很小,并且即使在角度突变的情况下,跟踪算法结合修正量测数据同样可以实现对目标的稳定跟踪。

关键词：目标跟踪角度突变奇异矩阵

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Catalytic alkane dehydrogenations

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Science Bulletin 2015年第15期60卷 1316-1331页

作者： Yuxuan zhang wubing Yao Huaquan Fang Aiguo Hu Zheng Huang Shanghai Key Laboratory of Advanced Polymeric Materials School of Materials Science and Engineering East China University of Science and Technology State Key Laboratory of Organometallic Chemistry Shanghai Institute of Organic Chemistry Chinese Academy of Sciences

Olefins find widespread applications in the synthesis of polyolefins and fine chemicals. With an increasing demand for olefins, the technologies for alkane dehydrogenation have drawn much attention. Several types of heterogeneous catalysts have found applications in industry for the dehydrogenation of light alkanes, mainly ethane, propane, and butane. In the past three decades, a number of transition-metal complexes,particularly pincer-ligated iridium complexes, have been developed as the homogeneous catalysts for alkane dehydrogenations. The homogeneous catalyst systems operate under much milder conditions compared with the heterogeneous systems, and some systems exhibit good activity and high regioselectivity in dehydrogenation of alkanes longer than butane.

关键词： Olefins Alkane dehydrogenation Heterogeneous catalysts Homogeneous catalysts Pincer ligand Iridium complexes

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Lipopolysaccharide/Toll-like receptor 4 signaling pathway involved Qingdu decoction treating severe liver injury merging with endotoxemia

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Journal of Traditional Chinese Medicine 2017年第3期37卷 371-377页

作者： Cao wubing Du Yuqiong Gao Lianyin Che Niancong zhang Qiuyun Fu Xiuwen Luo Jiajia Wang Rongbing Beijing Key Laboratory of Traditional Chinese Medicine Collateral Disease Theory Research Department of Clinical Foundation of Chinese MedicineSchool of Traditional Chinese MedicineCapital Medical UniversityBeijing 100069China Department of Traditional Chinese Medicine Longyou County People's HospitalZhejiang 324400China Department of Traditional Chinese Medicine Campus Hospital of Capital Medical UniversityBeijing 100069China Department of Integrated Traditional and Western Medicine Beijing Ditan Hospital Affiliated to Capital Medical UniversityBeijing 100015China

OBJECTIVE: To investigate the protective effects and underlying mechanism of Qingdu decoction(QDD) on experimental rats with severe liver injury induced by thioacetamide(TAA).METHODS: A total of 40 Wistar rats were randomly divided into normal group(n = 10) and experimental group(n = 30). Rats were administrated the same content of saline in normal group. The rats inthe experimental group were pretreated with TAA at dose of 12 mg/kg lasting 8 weeks, and from 9th week to 12 th week, with TAA at concentration of 36mg/kg. During the 9th week to 12 th week period,the rats were randomly divided into three subgroups(n = 10 each) simultaneously based on the treatment categories: model group, lactulose(LA,3.5 m L/kg) group and QDD(5.95 g/kg) group, orally once per day respectively. At the 12 th week, the content of serum alanine transaminase(ALT), aspartate transaminase(AST), total bilirubin(TBIL), endotoxin(ET) and tumor necrosis factor α(TNF-α) was detected by automatic biochemical analyzer. The plasma prothrombin time(PT), prothrombin time-international normalized ratio(PTR) and prothrombin time activity(PTA) were measured by automatic coagulation analyzer. The level of lipopolysaccharide(LPS)-binding protein(LBP), cluster differentiation 14(CD14) and Toll-like receptor 4(TLR4) expressions was measured by both western blot(WB) and real-time polymerase chain reaction(real-time PCR).RESULTS: Compared with the model group, hepatic morphology in the QDD group was improved under light microscope and transmission electron microscope; at the same time, the contents of serum ALT, AST, TBIL, ET and TNF-α, and level of LBP, CD14 and TLR4 expressions in liver tissues were significantly decreased compared with the model group(P < 0.05), while PTA in the QDD group was enhanced(P < 0.05).CONCLUSION: QDD has the functional effect on improving the injured liver through inhibiting the LPS/TLR4 signaling pathway thus decreasing the level of the inflammatory medicators.

关键词： Thioacetamide Lipopolysaccharides,Antigens, CD14 Toll-like receptor 4, Endotoxin

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Separation of Dopamine and Epinephrine by a Novel Electrophoresis Technique with Nafion Membrane as Separation Column

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Wuhan University Journal of Natural Sciences 2004年第1期9卷 102-104页

作者： FangCheng wubing-liang zhangWu-ming ZhouXing-yao CollegeofChemistryandMolecularSciences WuhanUniversityWuhan430072HubeiChina

A novel electrophoresis technique, in which a strip of perflurosulfonic-acid (nafion 117) membrane was used to replace the conventional separation column and liquid buffer solution within, was developed and employed to separate the mixture of dopamine and epinephrine under a low separation voltage of 100 V with quadruple pulses amperometry detection. It was showed that the so-called Nafion membrane electrophoresis could be one of very simple and easy method and has the potentiality to be used to separate and analyze some small organic biologic molecules. Key words nafion membrane - electrophoresis - electrochemical detector - dopamine - epinephrine CLC number O 657. 7 Foundation item: Support by the Foundation of Electroanalytical Chemistry Open Lab (203231510), Changchum, China.Biography: Fang Cheng (1971-), male, Lecture, Ph. D, research direction: Electroanalysis.

关键词： nafion membrane electrophoresis electrochemical detector dopamine epinephrine

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钴催化的高效贝克曼重排反应

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高等学校化学学报 2018年第5期39卷 926-933页

作者：姚武冰虞姜姜黄相韵张斌台州学院医药化工学院台州318000

利用廉价易得的氟硼酸钴水合物,在温和、无添加剂的空气条件下,高效催化酮肟衍生物的贝克曼重排反应,底物的普适性和官能团的兼容性均较理想,产物收率最高达97%.基于该高活性的氟硼酸钴水合物,实现了10 g级二苯甲酮肟的贝克曼重排反应,... 详细信息

利用廉价易得的氟硼酸钴水合物,在温和、无添加剂的空气条件下,高效催化酮肟衍生物的贝克曼重排反应,底物的普适性和官能团的兼容性均较理想,产物收率最高达97%.基于该高活性的氟硼酸钴水合物,实现了10 g级二苯甲酮肟的贝克曼重排反应,收率为71%.同时,也实现了钴催化酮类衍生物和盐酸羟胺的一步法贝克曼重排反应,产物最高收率为94%,反应体系中无溶剂及添加剂,反应体系的原子经济性和底物普适性较好.

关键词：贝克曼重排钴催化剂酮酮肟酰胺

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水性环氧树脂体系的研究进展

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涂料工业 2002年第8期32卷 28-30页

作者：张黎舒武炳西北工业大学化工系西安710072

总结了目前国内外水性环氧树脂体系的研究进展 ,并介绍了水性环氧涂料的制备方法与应用领域。

关键词：水性环氧树脂体系研究进展水性涂料乳化

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Toward Earth system modeling with resolved clouds and ocean submesoscales on heterogeneous many-core HPCs

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National Science Review 2023年第6期10卷 153-167页

作者： Shaoqing zhang Shiming Xu Haohuan Fu Lixin Wu Zhao Liu Yang Gao Chun Zhao wubing Wan Lingfeng Wan Haitian Lu Chenling Li Yanfei Liu Xiaojing Lv Jiayu Xie Yangyang Yu Jun Gu Xuantong Wang Yan zhang Chenhui Ning Yunlong Fei Xiuwen Guo Zhaoying Wang Xue Wang Zhenming Wang Binglin Qu Mingkui Li Haoran Zhao Yingjing Jiang Guang Yang Lv Lu Hong Wang Hong An Xin zhang Yu zhang Wentao Ma Fujiang Yu Jing Xu Xiaopei Lin Xueshun Shen Key Laboratory of Physical Oceanography Ministry of Education/Institute for Advanced Ocean Study/Frontiers Science Center for Deep Ocean Multispheres and Earth System (DOMES) College of Oceanic and Atmospheric Sciences Ocean University of China Laoshan Laboratory Ministry of Education Key Lab for Earth System Modeling and Department of Earth System Science Tsinghua University National Supercomputing Center in Wuxi Frontiers Science Center for Deep Ocean Multispheres and Earth System and Key Laboratory of Marine Environment and Ecology Ministry of Education Ocean University of China Deep Space Exploration Laboratory/School of Earth and Space Sciences University of Science and Technology of China School of Computer Science and Technology University of Science and Technology of China CEAKJ ADPRHexa Inc. National Marine Environmental Forecasting Center State Key Laboratory of Satellite Ocean Environment Dynamics Second Institute of Oceanography Ministry of Natural Resources Chinese Academy of Meteorological Sciences The Center of Earth System Modeling and Prediction China Meteorological Administration

With the aid of the newly developed ’Sunway’ heterogeneous-architecture supercomputer,which has world-leading HPC(high-performance computer) capability,a series of high-resolution coupled Earth system models(SW-HRESMs) with up to 5 km of atmosphere and 3 km of ocean have been *** models can meet the needs of multiscale interaction studies with different computational *** we describe the progress of SW-HRESMs development,with an overview of the major advancements made by the international Earth science community in *** also show the preliminary results of SW-HRESMs with regard to capturing major weather-climate extremes in the atmosphere and ocean,stressing the importance of permitted clouds and ocean submesoscale eddies in modeling tropical cyclones and eddy-mean flow interactions,and paving the way for further model development to resolve finer scales with even higher resolution and more realistic ***,in addition to increasing model resolution,the development procedure for a non-hydrostatic cloud and ocean submesoscale resolved ESM is discusse d,laying out the major scientific directions of such a huge modeling advancement.

关键词： high-resolution Earth system models heterogeneous supercomputer cloud and submesoscale resolving weather-climate extremes finer cross-scale interactions

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受众对国产中小成本电影的接受心理分析

受众对国产中小成本电影的接受心理分析

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作者：吴冰成都理工大学

学位级别：硕士

“中小成本电影”这一概念的提出,从严格意义上来讲,并不是一个被国际广泛认可与接受的专业术语[1]。其使用多是为了与“大片”区别开来,大片主要强调“大制作”、“大投资”、“大导演”和“大明星”,而国产中小成本电影则是与之相对... 详细信息

“中小成本电影”这一概念的提出,从严格意义上来讲,并不是一个被国际广泛认可与接受的专业术语[1]。其使用多是为了与“大片”区别开来,大片主要强调“大制作”、“大投资”、“大导演”和“大明星”,而国产中小成本电影则是与之相对的“中小投资”、“中小制作”。从“成本”两个字的定义范围来看,中小成本电影与其他电影的区别主要体现在投资成本上。一般而言,“中等成本影片”是指投资成本在1000万元至7000万元之间的,没有大量明星参演的影片;而“小成本影片”则是指那些投资成本在1000万元人民币以下,只有很少明星或几乎没有明星加入的影片。而近年来的国产中小成本电影,由于其制作越来越精良,明星参演越来越多,以至于制作成本略有上升,但相比国内外大片来说,投资额依然较低。相较于商业大片,中小成本电影在回收成本方面承受的压力明显要小很多。故而,这样的“轻装上阵”,对于积极探索电影创作的可能性和多样化是起到积极促进作用的[2]。中国电影市场在近年来呈现出的无限活力,正是得益于国产中小成本电影的推动力:徐峥、赵薇、邓超、韩寒、郭敬明等导演的处女作一一公映;姜文、侯孝贤、张艺谋、许鞍华等多位大导演不约而同地创作中小成本故事片,以低成本讲述中国的故事;类型化趋势越来越明显的公路喜剧片系列;以及受众定位越来越清晰化的“粉丝电影”系列,都在向我们展现一个更加丰富多彩、极具受众吸引力的国产中小成本电影业态。这既是机遇,也是挑战。给电影新人们提供了更低的准入门槛的同时,也提出了更高的艺术要求。给受众观影创造了更多选择的同时,也给受众带来了新的课题——怎样选择性消费国产中小成本电影。过去的2014年内地票房过亿元的影片已经接近70部,创下历史记录。在票房过亿的国产影片当中,《心花路放》以11.69亿的票房高居国产片首位。此外,细分之下,本年度的电影创作呈现进一步多元化的趋势。2014年的电影格局中,与以往相比,爱情电影一如既往获得了受众的喜爱,有走回忆青春路线的《同桌的你》、《匆匆那年》,有都市轻喜风格的《北京爱情故事》、《单身男女2》、《闺蜜》、《分手大师》,还有嫁接公路片的《后会无期》、《心花路放》等。可以看出,这些票房与口碑都有所斩获的国产片,几乎都是中小成本电影。这与往年在大片(无论是国外大片还是国产大片)的缝隙中生存并且逐步发展的境遇不同,2014年至2015年初,国产片几乎都是以中小成本电影的姿态出现,而且类型细分越来越明显,制作也越来越精良[3]。但是,当所有导演和编剧开始在中小成本电影这条道路上从摸索前进变为竞相奔跑的时候,我们需要停下来省视——难道所有类型的中小成本电影都卖座又叫好?难道一窝蜂地拍青春爱情、拍公路喜剧、拍黑色幽默、拍综艺节目,就真的能笼络受众的“芳心”?所有这些问题,能解答的只有国产中小成本电影的受众。而新媒介、新技术、新的社会文化环境下的受众本身也发生了很多变化。因此,笔者从受众接受心理的角度出发,去分析国产中小成本电影,并以丹尼斯·麦奎尔的受众分析观点对当前信息社会的受众做了新的解读与探讨,以期能够更加准确地把握现代国内受众对于近年来国产中小成本电影的接受心理[4]。本文第一章是绪论,介绍了本文研究的背景和选择这一论文题目的依据,以及所涉及的核心专业术语。对国产中小成本电影和国产中小成本电影的受众接受心理的相关文献作了综述,并说明了本文采用的研究方法与成文思路。第二章是国产中小成本电影的发展概况:第一阶段是上世纪80年代末90年代初开始,国产中小成本电影已经开始登上大银幕,并逐渐形成了一支较为强大的创作群体。第二阶段是2000年至2006年,一大批青年导演,如陆川、宁浩等,携他们极具自身生活感悟的中小成本电影处女作亮相,在当时产生了一定的影响力。第三阶段则是2006年至今,新媒体大数据时代的到来,不断更新的技术手段,使得这一阶段国产中小成本电影卖座又叫好[5]。第三章是对国产中小成本电影受众接受心理的调查结果进行的描述性统计分析,分别从国产中小成本电影受众的人口统计学特征、热门国产中小成本电影的观看情况、接受动机、观看途径、接受偏好这五个方面进行说明[6]。第四章为国产中小成本电影受众接受心理调查结果的定性分析,分析国产中小成本电影受众具有相关人口统计学特征的成因以及对国产中小成本电影受众的接受心理进行分析。第五章是国产中小成本电影满足受众接受心理的应对策略,通过对调查结果的分析,从受众的角度出发,给出了国产中小成本电影的相关建议。最后本文结语:国产中小成本电影近年来不仅打败国产大片,甚至与好莱坞大片相抗衡,并且保证了较好的票房收入与受众关注度。说明在新媒介环境下的“受众接受”也发生了变化,我们应该紧抓时代脉搏,在这场变革潮流中收获更多的叫好又卖座的国产中小成本电影,也收获更多受众的喜爱。

关键词：国产中小成本电影受众接受分析受众接受心理

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