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Clinical Success of Drug Targets Prospectively Predicted by In Silico Study

TRENDS IN PHARMACOLOGICAL SCIENCES 2018年第3期39卷 229-231页

作者： Zhu, Feng Li, Xiao Xu Yang, Sheng Yong Chen, Yu Zong Zhejiang Univ Coll Pharmaceut Sci Innovat Drug Res & Bioinformat Grp Hangzhou 310058 Zhejiang Peoples R China Chongqing Univ Sch Pharmaceut Sci Innovat Drug Res & Bioinformat Grp Chongqing 401331 Peoples R China Natl Univ Singapore Dept Pharm Bioinformat & Drug Design Grp Singapore 117543 Singapore Tsinghua Univ Grad Sch Shenzhen State Key Lab Breeding Base Shenzhen Key Lab Chem BiolShenzhen Kivita Innovat Drug Di Shenzhen 518055 Peoples R China Sichuan Univ State Key Lab Biotherapy Chengdu 610000 Sichuan Peoples R China

The selection of the right drug targets is critically important for the successful and cost-effective development and clinical testing of drugs. A 2009 paper reported an in silico prospective prediction of the clinical potential of 156 targets of clinical trial drugs (all of these targets were without an approved drug at the time of the paper's publication). Eight years later, the assessment of the clinical status of these targets revealed impressive capability of the in silico method in prospectively predicting the clinical success of drug targets.

关键词： clinical trial in silico methods target discovery

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Short Time high-Resistance State Instability of TaOx-Based RRAM Devices

IEEE ELECTRON DEVICE LETTERS

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IEEE ELECTRON DEVICE LETTERS 2017年第1期38卷 32-35页

作者： Li, Xinyi Wu, Huaqiang Gao, Bin Deng, Ning Qian, He Tsinghua Univ Inst Microelect Beijing 100084 Peoples R China

In this letter, TiN/TaOy/Ta2O5-x /Pt-based resistive switching devices were fabricated and tested. Short time high-resistance state instability phenomenon was observed during pulse programming verification measurement. This instability phenomenon was observed in about a minute after the RESET operation for high resistance states. In contrast, the measured low-resistance states after SET operation with current compliance >= 100 mu A are quite stable. This high resistance short time instability could cause incorrect write operations and reliability issues. Possible mechanisms were proposed to explain this high resistance states short time instability phenomenon of the TaOx-based resistive switching devices.

关键词： RRAM tantalum oxide short time instability dielectric relaxation

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development of a counterselectable seamless mutagenesis system in lactic acid bacteria

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MICROBIAL CELL FACTORIES 2017年第1期16卷 1-13页

作者： Xin, Yongping Guo, Tingting Mu, Yingli Kong, Jian Shandong Univ State Key Lab Microbial Technol 27 Shanda Nanlu Jinan 250100 Peoples R China

Background: Lactic acid bacteria (LAB) are receiving more attention to act as cell factories for the production of high-value metabolites. However, the molecular tools for genetic modifying these strains are mainly vector-based double-crossover strategies, which are laborious and inefficient. To address this problem, several counterselectable markers have been developed, while few of them could be used in the wild-type host cells without pretreatment. Results: The pheS gene encoding phenylalanyl-tRNA synthetase alpha subunit was identified in Lactococcus lactis NZ9000 genome. When mutant pheS gene (pheS*) under the control of the Lc. lactis NZ9000 (L)-lactate dehydrogenase promoter (P-ldh) was expressed from a plasmid, the resulted PheS* with an A312G substitution rendered cells sensitive to the phenylalanine analog p-chloro-phenylalanine (p-Cl-Phe). This result suggested pheS* was suitable to be used as a counterselectable marker in Lc. lactis. However, the expression level of pheS* from a chromosomal copy was too low to confer p-Cl-Phe sensitivity. Therefore, a strategy of cascading promoters was attempted for strengthening the expression level of pheS*. Expectedly, a cassette 5Pldh-pheS* with five tandem repetitive promoters P-ldh resulted in a sensitivity to 15 mM p-Cl-Phe. Subsequently, a counterselectable seamless mutagenesis system PheS*/pG(+) host9 based on a temperature-sensitive plasmid pG(vertical bar) host9 harboring a 5Pldh-pheS* cassette was developed in Lc. lactis. We also demonstrated the possibility of applying pheS* to be a counterselectable marker in Lactobacillus casei BL23. Conclusions: As reported in E. coli, pheS* as a counterselectable marker has been demonstrated to be functional in targeted gene(s) deletion in Lc. lactis as well as in L. casei. Moreover, the efficiency and timesaving counterselectable seamless mutagenesis system PheS*/pG(+) host9 could be used in the wild-type host cells without pretreatment.

关键词： Lactic acid bacteria Temperature-sensitive plasmid Seamless mutagenesis Counterselectable marker pheS

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Accelerated wound-healing capabilities of a dressing fabricated from silkworm cocoon

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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES 2017年 102卷 901-913页

作者： Yu, Kun Lu, Fei Li, Qing Zou, Yini Xiao, Yang Lu, Bitao Liu, Jiawei Dai, Fangying Wu, Dayang Lan, Guangqian Southwest Univ Coll Text & Garments Chongqing 400715 Peoples R China Chongqing Engn Res Ctr Biomat Fiber & Modern Text Chongqing 400715 Peoples R China Guangdong Acad Agr Sci Sericulture & Agrifood Res Inst Guangzhou 510610 Guangdong Peoples R China

Silk fibroin materials have shown some success in wound dressing applications;however, their use for this purpose remains limited by a complex production process and wasted sericin. In the present study, Bombyx mori cocoon materials are used because the protective function of the silkworm cocoon resembles the manner in which the skin protects the human body. A series of silkworm cocoon sol-gel film (SCSF) wound dressings are prepared by immersion in a CaCl2-ethanol-H2O solution for different treatment times. The accelerated wound-healing capabilities of SCSFs are systematically evaluated. Among them, the SCSF sample immersed for 90 min exhibits stronger biocompatibility and antibacterial performance compared to other SCSFs. SCSF-90 also exhibits excellent transparency, a high swelling ratio, and good extensibility. Furthermore, in vivo experiments indicate that SCSF-90 can significantly accelerate the healing rate of wounds in New Zealand white rabbits, compared to the standard Mepitel dressing, and histological examinations reveal that SCSF-90 aided in the successful reconstruction of intact and thickened epidermis. These results demonstrate that the proposed approach may be utilized in the design of antibacterial materials with promising applications in wound dressing. (C) 2017 Elsevier B.V. All rights reserved.

关键词： Silkworm cocoon Biocompatibility Wound healing

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Vshadow: Promoting Physical Servers into Virtualization World

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INTERNATIONAL JOURNAL OF PARALLEL programMING 2017年第1期45卷 45-66页

作者： Wu, Song Li, Yongchang Wang, Xinhou Jin, Hai Chen, Hanhua Huazhong Univ Sci & Technol Sch Comp Sci & Technol Serv Comp Technol & Syst Lab Wuhan 430074 Peoples R China Huazhong Univ Sci & Technol Sch Comp Sci & Technol Cluster & Grid Comp Lab Wuhan 430074 Peoples R China

Though virtualization technology has been widely adopted these years due to its advantages on improving server utilization, reducing management costs and energy consumption, there are still lots of legacy applications deployed in traditional physical machines. How to efficiently promote these physical servers into virtual machines (VMs) if necessary has become an interesting and challenging problem. Existing Physical-to-Virtual (P2V) conversion methods suffer from long server downtime during the converting process, which makes them impractical and inefficient in real world. In this paper, we analyze the reason why the previous approaches result in intolerable server downtime, and propose a new P2V conversion system called Vshadow. It enables a native P2V conversion which can quickly switch physical machine to a local VM, and combines implicit disk replication method and live migration process to promote physical machine into remote virtualization platform. Our experimental results show that Vshadow can reduce the server downtime by more than 90 % compared with existing P2V conversion methods. Besides proving the effectiveness and efficiency of Vshadow, we also illustrate the possible ways to apply Vshadow in server consolidation of cloud data centers and to use Vshadow to build a cost-effective failover system.

关键词： P2V Synchronization Live migration Consolidation Failover

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A Hardware-Friendly hierarchical HEVC Motion Estimation Algorithm for UHD Applications 50

A Hardware-Friendly Hierarchical HEVC Motion Estimation Algo...

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IEEE International Symposium on Circuits and Systems (ISCAS)

作者： Hu, Li Gu, Jiawei He, Guanghui He, Weifeng Shanghai Jiao Tong Univ Sch Microelect Shanghai Peoples R China

ISBN: (纸本)9781467368537

high Efficiency Video Coding (HEVC) standard has a superior video compression rate compared with previous H.264/AVC. At the same time, Ultra-high-definition (UHD) video applications are becoming a reality under the development of the display technology. In this paper, a hardware-friendly multilayer HEVC motion estimation (ME) algorithm for UHD applications are proposed. To keep the computational regularity of the traditional full-search (FS) ME algorithm as well as reduce the computational complexity of ME in a large search range (SR), the basic layer of the proposed algorithm is to combine FS scheme in a core area with downsampling search scheme in a large peripheral area. Moreover, the finer layer of the algorithm employs a hexagon search scheme to perform further ME around the optimal match point generated by the basic layer. Integrating the proposed algorithm into the HM 15.0, experimental results show that our hardware-friendly algorithm can achieve 97.8% of computations reduction while only 0.77% of BD-rate loss on average. Consequently, the proposed algorithm is feasible for HEVC ME hardware design for UHD applications.

关键词： Motion Estimation HEVC UHD Hardware-Friendly Algorithm

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A 0.2V 2.3pJ/Cycle 28dB Output SNR Hybrid Markov Random Field Probabilistic-Based Circuit for Noise Immunity and Energy Efficiency 50

A 0.2V 2.3pJ/Cycle 28dB Output SNR Hybrid Markov Random Fiel...

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IEEE International Symposium on Circuits and Systems (ISCAS)

作者： Jin, Xuwei Jin, Wei Zhang, Hao Jiang, Jianfei He, Weifeng Shanghai Jiao Tong Univ Sch Elect Informat & Elect Engn Shanghai Peoples R China

ISBN: (纸本)9781467368537

In this paper, two kinds of simplified cell structures for low voltage noise immunity and a hybrid Markov Random Field probabilistic-based circuit design technique are proposed to reduce the hardware overhead and improve the noise immunity. To demonstrate the proposed technique, four kinds of test chips with an 8-bit carry lookahead adder (CLA) are fabricated in a 130nm CMOS technology. Measurement results show the proposed hybrid MRF CLA improves 14% noise immunity, saves 53% energy consumption and reduces 11% circuit area than the other CLAs.

关键词： Markov random field (MRF) ultra-low voltage noise immunity energy efficiency

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A new electrospun graphene-silk fibroin composite scaffolds for guiding Schwann cells

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JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION 2017年第18期28卷 2171-2185页

作者： Zhao, Yahong Gong, Jiahuan Niu, Changmei Wei, Ziwei Shi, Jiaqi Li, Guohui Yang, Yumin Wang, Hongbo Jiangnan Univ Key Lab Sci & Technol Ecotext Minist Educ Wuxi Peoples R China Nantong Univ Key Lab Neuroregenerat Nantong Peoples R China Nantong Univ Coinnovat Ctr Neuroregenerat Nantong Peoples R China Nantong Univ Med Sch Nantong Peoples R China

Graphene (Gr) has been made of various forms used for repairing peripheral nerve injury with favorable electroactivity, however, graphene-based scaffolds in peripheral nerve regeneration are still rarely reported due to the difficulty of realizing uniform dispersion of graphene and electroactive materials at nanoscale as well as lacking biocompatibility. In this paper, graphene-silk fibroin (SF) composite nanofiber membranes with different mass ratios were prepared via electrospinning. Microscopic observation revealed that electrospun Gr/SF membranes had a nanofibrous structure. Electrochemical analysis provided electroactivity characterization of the Gr/SF membranes. The physiochemical results showed that the physiochemical properties of electrospun Gr/SF membranes could be changed by varying Gr concentration. Swelling ratio and contact angle measurements confirmed that electrospun Gr/SF membranes possessed large absorption capacity and hydrophilic surface, and the mechanical property was improved with increasing Gr concentration. Additionally, in-vitro cytotoxicity with L929 revealed that all the electrospun Gr/SF membranes are biocompatible. Moreover, the morphology and quantity showed that the membranes supported the survival and growth of the cultured Schwann cells. Collectively, all of the results suggest that the electrospun Gr/SF membranes combine the excellent electrically conductivity and mechanical strength of the graphene with biocompatibility property of silk to mimic the natural neural cell micro-environment for nerve development.

关键词： Electrospinning graphene silk fibroin electrical conductivity schwann cells

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In situ reduction of silver nanoparticles by chitosan-L-glutamic acid/hyaluronic acid: Enhancing antimicrobial and wound-healing activity

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CARBOHYDRATE POLYMERS 2017年 173卷 556-565页

作者： Lu, Bitao Lu, Fei Zou, Yini Liu, Jiawei Rong, Bao Li, Zhiquan Dai, Fangying Wu, Dayang Lan, Guangqian Southwest Univ Coll Text & Garments Chongqing 400715 Peoples R China Chongqing Engn Res Ctr Biomat Fiber & Modern Text Chongqing 400715 Peoples R China Ninth Peoples Hosp Chongqing Chongqing 400715 Peoples R China

Spongy composites with silver nanoparticles (AgNPs) were synthesized by freeze-drying a mixture of silver nitrate (AgNO3) and chitosan-L-glutamic acid (CG) derivative loaded with hyaluronic acid (HA) solution. CG/AgNP spongy composites had an interconnected porous structure and rough surfaces. When AgNPs (5-20 nm) were immobilized on these spongy composites, AgNP aggregation was dependent on AgNO3 concentration. The spongy composites exhibited good mechanical properties, swelling, and water retention capacity. In vitro antibacterial activity showed that the CG/AgNP spongy composites effectively inhibited bacterial (Escherichia coli and Staphylococcus aureus) growth and penetration. Spongy composites containing low concentrations of AgNP were non-toxic to L929 cells, while CG/HA/AgNP spongy composites promoted wound healing, as determined by in vivo tests, wound contraction ratio, average healing time, and histological examination. These results indicate that the spongy composites can serve as effective antibacterial wound dressings. (C) 2017 Elsevier Ltd. All rights reserved.

关键词： c-glutamic acid Chitosan Ag nanoparticles Antimicrobial Wound dressing

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An advance for removing antinutritional protease inhibitors: Soybean whey purification of Bowman-Birk chymotrypsin inhibitor by combination of two oppositely charged polysaccharides

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CARBOHYDRATE POLYMERS 2017年 164卷 349-357页

作者： Li, Xingfei Hua, Yufei Chen, Yeming Kong, Xiangzhen Zhang, Caimeng Yu, Xiaobin Jiangnan Univ Sch Food Sci & Technol State Key Lab Food Sci & Technol 1800 Lihu Ave Wuxi 214122 Jiangsu Peoples R China Jiangnan Univ Sch Biotechnol Key Lab Ind Biotechnol Minist Educ Wuxi 214122 Peoples R China

Two successive and selective coacervations induced by chitosan (Ch) and carrageenan (CG) were applied to remove antinutritional protease inhibitors and purify Bowman Birk protease inhibitor (BBI) from soybean whey. At the first coacervation induced by Ch (66.7, 200, and 510 kDa), only Kunitz trypsin inhibitor (KTI) and BBI complexed with Ch were extracted, while beta-amylase and soybean agglutinin remained in supernatant. The binding constants for the interaction increased on the order Ch-66.7 < Ch 200 < Ch-510. At the second selective complexation, we observed a competitive binding behavior between KTI/BBI and CG. At a mixing weight ratio of 3:1 (pH 3.0 for r-CG, and pH 3.11 for lambda-CG), the preferential binding of KTI to CG led to the single enrichment of BBI in the supernatant. Our results indicated that the purified BBI was a good source for further study of its anti-carcinogenic properties, due to its high bioactivity (669.5 U/mg chymotrypsin-inhibitory activity and 2260 U/mg trypsin-inhibitory activity). (C) 2017 Elsevier Ltd. All rights reserved.

关键词： Complex coacervation Soybean whey proteins Chitosan Carrageenan Trypsin inhibitory activity Chymotrypsin inhibitory activity

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