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Genetically Encoded Epoxide Warhead for Precise and Versatile Covalent Targeting of Proteins

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 2024年第23期146卷 16173-16183页

作者： Zhang, Jinpeng Wang, Xia Huang, Qingjun Ye, Jinsong Wang, Jie Southern Univ Sci & Technol Coll Sci Res Ctr Chem Biol & Omics Anal Dept ChemGuangdong Prov Key Lab Catalysis Shenzhen 518055 Peoples R China

Genetically encoding a proximal reactive warhead into the protein binder/drug has emerged as an efficient strategy for covalently binding to protein targets, enabling broad applications. To expand the reactivity scope for targeting the diverse natural residues under physiological conditions, the development of a genetically encoded reactive warhead with excellent stability and broad reactivity is highly desired. Herein, we reported the genetic encoding of epoxide-containing tyrosine (EPOY) for developing covalent protein drugs. Our study demonstrates that EPOY, when incorporated into a nanobody (KN035), can cross-link with different side chains (mutations) at the same position of PD-L1 protein. Significantly, a single genetically encoded reactive warhead that is capable of covalent and site-specific targeting to 10 different nucleophilic residues was achieved for the first time. This would largely expand the scope of covalent warhead and inspire the development of covalent warheads for both small-molecule drugs and protein drugs. Furthermore, we incorporate the EPOY into a designed ankyrin repeat protein (Darpin(K13)) to create the covalent binders of KRAS. This covalent KRAS binder holds the potential to achieve pan-covalent targeting of KRAS based on the structural similarity among all oncogenic KRAS mutants while avoiding off-target binding to NRAS/HRAS through a covalent interaction with KRAS-specific residues (H95 and E107). We envision that covalently targeting to H95 will be a promising strategy for the development of covalent pan-KRAS inhibitors in the future.

关键词： Monomers Nucleic acid structure Peptides and proteins Reactivity Targeting

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A Third-Order Majorization Algorithm for Logistic Regression With Convergence Rate Guarantees

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IEEE SIGNAL PROCESSING LETTERS 2024年 31卷 1700-1704页

作者： Zhao, Licheng Pu, Wenqiang Zhou, Rui Shi, Qingjiang Shenzhen Res Inst Big Data Shenzhen 518172 Peoples R China Tongji Univ Sch Software Engn Shanghai 201804 Peoples R China Shenzhen Res Inst Big Data Shenzhen 518172 Peoples R China

In this paper, we study the classical Logistic Regression (LR) problem in machine learning. Traditionally, the solving algorithms are based on either the first- or second-order approximation of the objective. For instance, the Fixed-Hessian Newton (FHN) method approximates the true Hessian with a constant estimate. In contrast, our design additionally exploits the third-order information. Applying the majorization-minimization (MM) framework, we construct a novel majorizing function based on the third-order Taylor expansion and the minimization solution is in closed-form with perseverance of the true gradient and Hessian structures. In analysis, we prove the convergence rate of the proposed algorithm. The enhanced numerical performance can be verified through simulation results.

关键词： Signal processing algorithms Minimization Convergence Optimization Taylor series Machine learning algorithms Logistic regression Convergence rate logistic regression majorization-minimization third-order

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Sensorless Control of Permanent Magnet Synchronous Motor Based on Adaptive Sliding Mode Observer and Phase Locked Loop 10

Sensorless Control of Permanent Magnet Synchronous Motor Bas...

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10th International Conference on Power Electronics Systems and Applications (PESA)

作者： An, Jiahao Zhang, Zhang Pan, Jianfei Shenzhen Univ Coll Mechatron & Control Engn Shenzhen Peoples R China

ISBN: (纸本)9798350365818;9798350365801

Traditional sensor-based control of the Permanent Magnet Synchronous Motor (PMSM) has several issues such as increased cost and volume, reduced reliability, etc. Sensorless control overcomes these problems and adding the magnetic chain observers, such as Sliding Mode Observer (SMO), is one of the control methods. Different from the traditional SMO, an adaptive SMO based on Phase Locked Loop (PLL) for sensorless control of the PMSM in this paper solves the problem of the slow position tracking speed and suppresses the serious chattering. The proposed method is realized by the co-simulation between MATLAB/Simulink and ANSYS, which not only verifies the correctness of the method, but also shows the tracking time levels down to 0.06 s and the chattering phenomena is effectively suppressed to 0.03 rad.

关键词： Permanent Magnet Synchronous Motor Phase-locked Loop Sliding Mode Observer Co-simulation

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BiVO4/boron-doped diamond heterojunction photoanode with boron doping engineering and enhanced photoelectrocatalytic activity

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DIAMOND AND RELATED MATERIALS 2023年第1期138卷

作者： Huang, Jiangtao Meng, Aiyun Zhang, Zongyan Ma, Guanjie Long, Yuhao Li, Xingyu Xiang, Bingxi Han, Peigang He, Bin Shenzhen Technol Univ Coll New Mat & New Energies Shenzhen 518118 Peoples R China Shenzhen Technol Univ Univ Engn Res Ctr Crystal Growth & Applicat Guangd Shenzhen 518118 Peoples R China

Photoelectrocatalysis is one of the most promising strategies to address ever-growing wastewater problems. A novel heterojunction photoanode formed by depositing a photocatalyst on a boron-doped diamond (BDD) layer has been considered an ideal material for the practical application of photoelectrocatalytic (PEC) degradation due to its advantages of light responsiveness, excellent charge transport, and robustness. In this study, various BiVO4/BDD heterojunction photoanodes with different diamond crystalline qualities and electrical conductivities were successfully fabricated by tuning the boron (B) doping concentration of the BDD layer. It was proposed that the charge transport efficiency of the photoanodes is promoted by optimizing the crystalline qualities and electrical conductivities of BDD films, thereby enhancing the PEC activity of the BiVO4/BDD heterojunction photoanode. Our results suggested that the electrical conductivity of BDD increased and the crystalline quality of BDD deteriorated with increasing B doping concentration. As a result, the PEC activity of the BiVO4/BDD het-erojunction photoanode first increased and then decreased. The optimal PEC activity of the BiVO4/BDD heter-ojunction photoanode was achieved corresponding to the [B]/[C] gas ratio at 500 ppm, producing a current density of 3.3 mA/cm2 at 1.6 VRHE (the potential versus a reversible hydrogen electrode) in 0.1 M Na2SO4 under AM 1.5 irradiation, which was 1.7 times (1.9 mA/cm2) that of the photoanode with a [B]/[C] gas ratio of 3000 ppm. Meanwhile, the optimized tetracycline hydrochloride (TCH) degradation efficiency was 63.5 % within 9 min (500 ppm gas phase), which was 2.5 times (25.1 %) that of the highly doped photoanode with a [B]/[C] gas ratio of 3000 ppm. This study revealed that the excellent PEC performance benefited from the high crystalline quality and high electrical conductivity of BDD, which depended on the optimized B doping concentration. The idea of enhancing the PEC activi

关键词： Boron-doped diamond (BDD) BiVO4 Heterojunction photoanode Photoelectrocatalytic (PEC) Tetracycline hydrochloride (TCH) degradation

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The (Phosphino)(stannyl)carbene

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CHEMICAL COMMUNICATIONS 2024年第72期60卷 9793-9796页

作者： Wei, Rui Wang, Xin-Feng Hu, Chaopeng Liu, Liu Leo Southern Univ Sci & Technol Coll Sci Dept Chem Shenzhen Peoples R China Southern Univ Sci & Technol Coll Sci Res Ctr Chem Biol & Om Anal Shenzhen Peoples R China

The synthesis of a (phosphino)(stannyl)carbene is documented. The combination of phosphino and stannyl substituents imparts a highly ambiphilic nature to this carbene, enabling reactions with cyanide, isocyanide, and ...

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Transformer-based material recognition via short-time contact sensing

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PATTERN RECOGNITION 2025年 163卷

作者： Liu, Zhenyang Shao, Yitian Li, Qiliang Su, Jingyong Harbin Inst Technol Shenzhen Sch Comp Sci & Technol Shenzhen 518055 Guangdong Peoples R China Great Bay Univ Sch Engn Dongguan 523000 Guangdong Peoples R China Peking Univ Coll Engn Dept Adv Mfg & Robot Beijing 100871 Peoples R China

Embodied intelligence needs haptic sensing for spontaneous and accurate material recognition. The haptic sensing module of an intelligent system can acquire material data through either sliding or tapping motions. Sliding movements are commonly adopted for collecting the spatial frequency features of the material but are less time-efficient than tapping. Here, we introduce a haptic sensing framework that can extract material features from short-time tapping signals. To improve the performance of material recognition, transfer learning is used by transferring the knowledge of pretrained model training on large-scale images into haptic sensing. The waveforms of the tapping signals are encoded as images to be input into a transformer model tailored for image recognition tasks. The encoding employs line graph image-point scaling, effectively accommodating signals that exhibit large variations in magnitude and temporal structures. Using the LMT haptic material database containing sliding and tapping data, our study showcases the efficacy of the proposed framework in material recognition tasks, especially for short-time (<= 60 ms) sensing via tapping interactions. The findings provide fresh insights into haptic sensing technologies and may help improve the physical interaction capabilities of embodied intelligence, such as medical and rescue robots.

关键词： Haptic sensing Time series-to-image encoding Transfer learning Vision transformer Material recognition

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Study on the impact of bowtie filter on photon-counting CT imaging

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PHYSICS IN MEDICINE AND BIOLOGY 2024年第21期69卷 215033-215033页

作者： Zhang, Xin Xie, Jixiong Su, Ting Zhu, Jiongtao Xia, Dongmei Zheng, Hairong Liang, Dong Ge, Yongshuai Chinese Acad Sci Shenzhen Inst Adv Technol Res Ctr Adv Detect Mat & Med Imaging Devices Shenzhen 518055 Guangdong Peoples R China Univ Chinese Acad Sci Beijing 100049 Peoples R China Chongqing Univ Coll Power Engn Key Lab Low Grade Energy Utilizat Technol & Syst Minist Educ China Chongqing 400044 Peoples R China Chinese Acad Sci Shenzhen Inst Adv Technol Paul C Lauterbur Res Ctr Biomed Imaging Shenzhen 518055 Guangdong Peoples R China Key Lab Biomed Imaging Sci & Syst Shenzhen 518055 Guangdong Peoples R China Chinese Acad Sci Shenzhen Inst Adv Technol Res Ctr Med Artificial Intelligence Shenzhen 518055 Guangdong Peoples R China Natl Innovat Ctr Adv Med Devices Shenzhen 518131 Guangdong Peoples R China

Objective. The aim of this study was to investigate the impact of the bowtie filter on the image quality of the photon-counting detector (PCD) based CT imaging. Approach. Numerical simulations were conducted to investigate the impact of bowtie filters on image uniformity using two water phantoms, with tube potentials ranging from 60 to 140 kVp with a step of 5 kVp. Subsequently, benchtop PCD-CT imaging experiments were performed to verify the observations from the numerical simulations. Additionally, various correction methods were validated through these experiments. Main results. It was found that the use of a bowtie filter significantly alters the uniformity of PCD-CT images, depending on the size of the object and the x-ray spectrum. Two notable effects were observed: the capping effect and the flattening effect. Furthermore, it was demonstrated that the conventional beam hardening correction method could effectively mitigate such non-uniformity in PCD-CT images, provided that dedicated calibration parameters were used. Significance. It was demonstrated that the incorporation of a bowtie filter results in varied image artifacts in PCD-CT imaging under different conditions. Certain image correction methods can effectively mitigate and reduce these artifacts, thereby enhancing the overall quality of PCD-CT images.

关键词： bowtie filter photon-counting detector CT imaging

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Mobius edge band and Weyl-like semimetal flat-band in topological photonic waveguide array by synthetic gauge flux

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NANOPHOTONICS 2023年第17期12卷 3481-3490页

作者： Liu, Zhenzhen Wei, Guochao Wu, Huizhou Xiao, Jun-Jun Harbin Inst Technol Shenzhen Coll Elect & Informat Engn Shenzhen 518055 Peoples R China Harbin Inst Technol Shenzhen Shenzhen Engn Lab Aerosp Detect & Imaging Shenzhen 518055 Peoples R China Wuhan Text Univ Sch Math & Phys Sci Wuhan 430200 Peoples R China

The presence of p gauge flux enabled by positive and negative hopping amplitude can lead to Mobius bands, which was recently demonstrated in both realistic acoustic and photonic lattices, twisted at k = p. Here, we show that the artificial gauge flux configuration can be achieved by exploiting the interactions between photonic s and p orbital-like fundamental modes in circular and peanut-shaped waveguides, respectively. By manipulating the interplay between the gauge fields and the crystal symmetry, we show that breaking the primitive translation symmetry through lattice site dimerization and deformation can cause the original Dirac semimetal phase, characterized by a four-fold Dirac point at the Brillouin zone center, to transform into various topological phases. The designed photonic waveguide array supports topological phases such as Mobius insulator and Weyl-like semimetal phases. Noticeably different to the existing cases, we explicitly show that the twisting Mobius bands cross each other at k = 0 due to the lattice gauging with alternating sign, which results in distinct beam dynamics excitation. We also present Weyl-like flat-band edge states in such photonics waveguide arrays. Our results suggest that such s - p hybridized photonic waveguide array servers as a convenient and flexible platform for studying topological physics, particularly in simulating the effects of gauge field in alternative configuration.

关键词： artificial gauge field beam dynamics Mobius insulator photonic waveguide Weyl semimetal

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Functional Connectivity Differences in the Resting-state of the Amygdala in Alcohol-dependent Patients with Depression

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ACADEMIC RADIOLOGY 2024年第11期31卷 4611-4620页

作者： Sun, Fengwei Kong, Zhi Tang, Yun Yang, Jihui Huang, Gengdi Liu, Yu Jiang, Wentao Yang, Mei Jia, Xiaojian Shenzhen Kangning Hosp Shenzhen Clin Res Ctr Mental Disorders Dept Addict Med Shenzhen 518020 Peoples R China Shenzhen Mental Hlth Ctr Shenzhen Guangdong Peoples R China Shenzhen Univ Clin Coll Mental Hlth Hlth Sci Ctr Shenzhen Peoples R China Southern Univ Sci & Technol Affiliated Mental Hlth Ctr Shenzhen 518118 Peoples R China Shenzhen Kangning Hosp Shenzhen Clin Res Ctr Mental Disorders Dept Radiol Shenzhen Peoples R China Shenzhen Univ Clin Coll Mental Hlth Hlth Sci Ctr Shenzhen 518118 Peoples R China Southern Univ Sci & Technol Affiliated Mental Hlth Ctr Shenzhen 518118 Peoples R China

Rationale and Objectives: The mechanism of comorbidity between alcohol dependence and depressive disorders are not well understood. This study investigated differences in the brain function of alcohol-dependent patients with and without depression by performing functional connectivity analysis using resting-state functional magnetic resonance imaging. Materials and Methods: A total of 29 alcohol-dependent patients with depression, 31 alcohol-dependent patients without depression and 31 healthy control subjects were included in this study. The resting-state functional connectivity between the amygdala and the whole brain was compared among the three groups. Additionally, we examined the correlation between functional connectivity values in significantly different brain regions and levels of alcohol dependence and depression. Results: The resting-state functional connectivity between the left amygdala and the right caudate nucleus was decreased in alcohol- dependent patients. Additionally, the resting-state functional connectivity of the right amygdala with the right caudate nucleus, right transverse temporal gyrus, right temporal pole: superior temporal gyrus were also decreased. In alcohol-dependent patients with depression, not only was functional connectivity between the above brain regions significantly decreased, but so was functional connectivity between the right amygdala and the left middle temporal gyrus. Also, there was no significant correlation between the resting- state functional connectivity values in statistically significant brain regions and the levels of alcohol dependence and depression. Conclusion: The impairment of the functional connectivity of the amygdala with caudate nucleus and partial temporal lobe may be involved in the neural mechanism of alcohol dependence comorbidity depressive disorders.

关键词： Alcohol dependence Amygdala Depression Functional connectivity Resting-state functional magnetic resonance imaging

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GNSS PPP with added QZSS: Positioning and time-frequency transfer

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ADVANCES IN SPACE RESEARCH 2023年第11期71卷 4485-4497页

作者： Ouyang, Mingjun Zhu, Xiangwei Yi, Ruite Shen, Dan Xie, Ting Li, Junzhi Sun Yat Sen Univ Shenzhen Key Lab Nav & Commun Integrat Shenzhen 528406 Peoples R China Sun Yat Sen Univ Sch Elect & Commun Engn Shenzhen 528406 Peoples R China Sun Yat Sen Univ Sch Syst Sci & Engn Shenzhen 528406 Peoples R China

Regional navigation system Quasi-Zenith Satellite System (QZSS) play an important role in positioning, time and frequency transfer for the Asia-Pacific region under high cut-off angle. This paper combines QZSS and the major navigation systems for Precise Point Positioning (PPP) positioning and time-frequency transfer. The time-frequency transfer experimental results show that with the addition of QZSS, the clock difference accuracy and the frequency stability of the corresponding time link are significantly improved for the case of cut-off above 15 degrees. The corresponding range is between 5% and 30% of accuracy, and between 1% and 90% of frequency stability. (c) 2023 COSPAR. Published by Elsevier B.V. All rights reserved.

关键词： QZSS Time-frequency transfer Precise point positioning

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