Based on BERTopic Model,the paper combines qualitative and quantitative methods to explore the reception of Can Xue’s translated works by analyzing readers’book reviews posted on Goodreads and Lovereading.We first c...Based on BERTopic Model,the paper combines qualitative and quantitative methods to explore the reception of Can Xue’s translated works by analyzing readers’book reviews posted on Goodreads and Lovereading.We first collected book reviews from these two well-known websites by Python.Through topic analysis of these reviews,we identified recurring topics,including details of her translated works and appreciation of their translation quality.Then,employing sentiment and content analysis methods,the paper explored the emotional attitudes and the specific thoughts of readers toward Can Xue and her translated works.The fingdings revealed that,among the 408 reviews,though the reception of Can Xue’s translated works was relatively positive,the current level of attention and recognition remains insufficient.However,based on the research results,the paper can derive valuable insights into the translation and dissemination processes such as adjusting translation and dissemination strategies,so that the global reach of Chinese literature and culture can be better facilitated.展开更多
Background:The precise insertion of large DNA fragments(>3–5 kb)remains one of the key obstacles in establishment of genetically modified murine models.Methods:A 21 kb large DNA fragment containing three tandemly ...Background:The precise insertion of large DNA fragments(>3–5 kb)remains one of the key obstacles in establishment of genetically modified murine models.Methods:A 21 kb large DNA fragment containing three tandemly linked copies of the human HRAS gene was inserted into the genome of C57BL/6J mouse,generating a mouse model designated as KI.C57-ras(or named NF-h HRAS).Whole-genome sequencing and Sanger sequencing were utilized to it confirm precise insertion and copy number.The stability of transgene expression among different generations was verified from multiple aspects using by digital PCR,western blot and DNA sequencing.To assess tumor susceptibility in the mouse model,N-Nitroso-N-methylurea(MNU)was administered at a dosage of 75 mg/kg.Histopathological examinations were conducted using hematoxylin and eosin(H&E)staining.Results:The HRAS DNA fragment was inserted into mouse chromosome 15E1 site,locating between 80623202 bp and 80625020 bp.NF-h HRAS mice exhibited stable inheritance and displayed consistent phenotypes across individuals.Moreover,this mouse model exhibited a high susceptibility to carcinogens.Upon administration of MNU the earliest mortality onset was earlier than that of wild-type littermates(day 65 vs.day 78 for male and day 56 vs.day 84 for female).Notably,100%of the NF-h HRAS transgenic mice developed tumors,with approximately 84%of male NF-h HRAS mice exhibiting specific tumor types,such as squamous cell carcinoma or squamous cell papilloma,which was consistent with the previously reported carcinogenic rasH2 mouse model.The types of tumors and the target organs exhibited diversity in NFh HRAS mice,while the spontaneous tumor incidence remained low(1/50).Conclusions:The NF-h HRAS mice demonstrated excellent genetic stability,a reproducible phenotype,and high susceptibility to carcinogens,indicating their potential utility in non-clinical safety evaluations of drugs as per the S1B guidelines issued by the ICH(The International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use).展开更多
Biophysical computational models are complementary to experiments and theories,providing powerful tools for the study of neurological diseases.The focus of this review is the dynamic modeling and control strategies of...Biophysical computational models are complementary to experiments and theories,providing powerful tools for the study of neurological diseases.The focus of this review is the dynamic modeling and control strategies of Parkinson’s disease(PD).In previous studies,the development of parkinsonian network dynamics modeling has made great progress.Modeling mainly focuses on the cortex-thalamus-basal ganglia(CTBG)circuit and its sub-circuits,which helps to explore the dynamic behavior of the parkinsonian network,such as synchronization.Deep brain stimulation(DBS)is an effective strategy for the treatment of PD.At present,many studies are based on the side effects of the DBS.However,the translation from modeling results to clinical disease mitigation therapy still faces huge challenges.Here,we introduce the progress of DBS improvement.Its specific purpose is to develop novel DBS treatment methods,optimize the treatment effect of DBS for each patient,and focus on the study in closed-loop DBS.Our goal is to review the inspiration and insights gained by combining the system theory with these computational models to analyze neurodynamics and optimize DBS treatment.展开更多
Ca^2＋ dysregulation is an early event observed in Alzheimer＇s disease（AD） patients preceding the presence of its clinical symptoms.Dysregulation of neuronalCa^2＋ will cause synaptic loss and neuronal death,eventu...Ca^2＋ dysregulation is an early event observed in Alzheimer＇s disease（AD） patients preceding the presence of its clinical symptoms.Dysregulation of neuronalCa^2＋ will cause synaptic loss and neuronal death,eventually leading to memory impairments and cognitive decline.Treatments targetingCa^2＋ signaling pathways are potential therapeutic strategies against AD.The complicated interactions make it challenging and expensive to study the underlying mechanisms as to how Ca^2＋ signaling contributes to the pathogenesis of AD.Computational modeling offers new opportunities to study the signaling pathway and test proposed mechanisms.In this mini-review,we present some computational approaches that have been used to study Ca^2＋ dysregulation of AD by simulating Ca^2＋signaling at various levels.We also pointed out the future directions that computational modeling can be done in studying the Ca^2＋ dysregulation in AD.展开更多
Aim: The objects of this study originated from the experimental observations, whereby the HIV -1 gp120 V3 loop is a high-affinity ligand for immunophilins, and consisted in generating the structural complex of cycloph...Aim: The objects of this study originated from the experimental observations, whereby the HIV -1 gp120 V3 loop is a high-affinity ligand for immunophilins, and consisted in generating the structural complex of cyclophilin (Cyc) B belonging to immunophilins family with the virus subtype A V3 loop (SA-V3 loop) as well as in specifying the Cyc B segment forming the binding site for V3 synthetic copy of which, on the assumption of keeping the 3D peptide structure in the free state, may present a forwardlooking basic structure for anti-AIDS drug development. Methods: To reach the objects of view, molecular docking of the HIV-1 SA-V3 loop structure determined previously with the X-ray conformation of Cyc B was put into practice by Hex 4.5 program (http://www.loria.fr/~ritchied/ hex/) and the immunophilin stretch responsible for binding to V3 (Cyc B peptide) was identified followed by examination of its 3D structure and dynamic behavior in the unbound status. To design the Cyc B peptide, the X-ray conformation for the identical site of the native protein was involved in the calculations as a starting model to find its best energy structural variant. The search for this most preferable structure was carried out by consecutive use of the molecular mechanics and simulated annealing methods. The molecular dynamics computations were implemented for the Cyc B peptide by the GROMACS computer package (http:// www.gromacs.org/). Results: The overmolecular structure of Cyc B with V3 was built by computer modeling tools and the immunophilinderived peptide able to mask effectively the structurally invariant V3 segments embracing the functionally crucial amino acids of the HIV-1 gp120 envelope protein was constructed and analyzed. Conclusions: Starting from the joint analysis of the results derived with those of the literature, the generated peptide was suggested to offer a promising basic structure for making a reality of the protein engineering projects aimed at developing the anti-AIDS drugs able to stop the HIV’s spread.展开更多
在对软件构架和B/S应用程序体系结构的研究过程中,提出了如何运用构架和构件组装技术,通过对可复用构件的组装进行B/S应用程序的设计和快速开发。文章拟以C2构架风格作为在整合应用系统的业务逻辑的基础设施,以B/S Model 2作为表示层的...在对软件构架和B/S应用程序体系结构的研究过程中,提出了如何运用构架和构件组装技术,通过对可复用构件的组装进行B/S应用程序的设计和快速开发。文章拟以C2构架风格作为在整合应用系统的业务逻辑的基础设施,以B/S Model 2作为表示层的框架原型,提出一种基于构架和构件的B/S结构模型,称为CB Model。并且介绍在研究过程中开发的组装支持工具BSAppBuilder。展开更多
基金supported by the 2023 Youth Fund for Humanities and Social Sciences Research by the Ministry of Education of the People’s Republic of China(Grant No.23YJC740004).
文摘Based on BERTopic Model,the paper combines qualitative and quantitative methods to explore the reception of Can Xue’s translated works by analyzing readers’book reviews posted on Goodreads and Lovereading.We first collected book reviews from these two well-known websites by Python.Through topic analysis of these reviews,we identified recurring topics,including details of her translated works and appreciation of their translation quality.Then,employing sentiment and content analysis methods,the paper explored the emotional attitudes and the specific thoughts of readers toward Can Xue and her translated works.The fingdings revealed that,among the 408 reviews,though the reception of Can Xue’s translated works was relatively positive,the current level of attention and recognition remains insufficient.However,based on the research results,the paper can derive valuable insights into the translation and dissemination processes such as adjusting translation and dissemination strategies,so that the global reach of Chinese literature and culture can be better facilitated.
基金National Key R&D Program of China,Grant/Award Number:2023YFC3402000National Institutes for Food and Drug Control,State Key Laboratory of Drug Regulatory Science,Grant/Award Number:2023SKLDRS0124。
文摘Background:The precise insertion of large DNA fragments(>3–5 kb)remains one of the key obstacles in establishment of genetically modified murine models.Methods:A 21 kb large DNA fragment containing three tandemly linked copies of the human HRAS gene was inserted into the genome of C57BL/6J mouse,generating a mouse model designated as KI.C57-ras(or named NF-h HRAS).Whole-genome sequencing and Sanger sequencing were utilized to it confirm precise insertion and copy number.The stability of transgene expression among different generations was verified from multiple aspects using by digital PCR,western blot and DNA sequencing.To assess tumor susceptibility in the mouse model,N-Nitroso-N-methylurea(MNU)was administered at a dosage of 75 mg/kg.Histopathological examinations were conducted using hematoxylin and eosin(H&E)staining.Results:The HRAS DNA fragment was inserted into mouse chromosome 15E1 site,locating between 80623202 bp and 80625020 bp.NF-h HRAS mice exhibited stable inheritance and displayed consistent phenotypes across individuals.Moreover,this mouse model exhibited a high susceptibility to carcinogens.Upon administration of MNU the earliest mortality onset was earlier than that of wild-type littermates(day 65 vs.day 78 for male and day 56 vs.day 84 for female).Notably,100%of the NF-h HRAS transgenic mice developed tumors,with approximately 84%of male NF-h HRAS mice exhibiting specific tumor types,such as squamous cell carcinoma or squamous cell papilloma,which was consistent with the previously reported carcinogenic rasH2 mouse model.The types of tumors and the target organs exhibited diversity in NFh HRAS mice,while the spontaneous tumor incidence remained low(1/50).Conclusions:The NF-h HRAS mice demonstrated excellent genetic stability,a reproducible phenotype,and high susceptibility to carcinogens,indicating their potential utility in non-clinical safety evaluations of drugs as per the S1B guidelines issued by the ICH(The International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use).
基金Project supported by the National Natural Science Foundation of China(Nos.11932003 and 11772019)。
文摘Biophysical computational models are complementary to experiments and theories,providing powerful tools for the study of neurological diseases.The focus of this review is the dynamic modeling and control strategies of Parkinson’s disease(PD).In previous studies,the development of parkinsonian network dynamics modeling has made great progress.Modeling mainly focuses on the cortex-thalamus-basal ganglia(CTBG)circuit and its sub-circuits,which helps to explore the dynamic behavior of the parkinsonian network,such as synchronization.Deep brain stimulation(DBS)is an effective strategy for the treatment of PD.At present,many studies are based on the side effects of the DBS.However,the translation from modeling results to clinical disease mitigation therapy still faces huge challenges.Here,we introduce the progress of DBS improvement.Its specific purpose is to develop novel DBS treatment methods,optimize the treatment effect of DBS for each patient,and focus on the study in closed-loop DBS.Our goal is to review the inspiration and insights gained by combining the system theory with these computational models to analyze neurodynamics and optimize DBS treatment.
文摘Ca^2＋ dysregulation is an early event observed in Alzheimer＇s disease（AD） patients preceding the presence of its clinical symptoms.Dysregulation of neuronalCa^2＋ will cause synaptic loss and neuronal death,eventually leading to memory impairments and cognitive decline.Treatments targetingCa^2＋ signaling pathways are potential therapeutic strategies against AD.The complicated interactions make it challenging and expensive to study the underlying mechanisms as to how Ca^2＋ signaling contributes to the pathogenesis of AD.Computational modeling offers new opportunities to study the signaling pathway and test proposed mechanisms.In this mini-review,we present some computational approaches that have been used to study Ca^2＋ dysregulation of AD by simulating Ca^2＋signaling at various levels.We also pointed out the future directions that computational modeling can be done in studying the Ca^2＋ dysregulation in AD.
文摘Aim: The objects of this study originated from the experimental observations, whereby the HIV -1 gp120 V3 loop is a high-affinity ligand for immunophilins, and consisted in generating the structural complex of cyclophilin (Cyc) B belonging to immunophilins family with the virus subtype A V3 loop (SA-V3 loop) as well as in specifying the Cyc B segment forming the binding site for V3 synthetic copy of which, on the assumption of keeping the 3D peptide structure in the free state, may present a forwardlooking basic structure for anti-AIDS drug development. Methods: To reach the objects of view, molecular docking of the HIV-1 SA-V3 loop structure determined previously with the X-ray conformation of Cyc B was put into practice by Hex 4.5 program (http://www.loria.fr/~ritchied/ hex/) and the immunophilin stretch responsible for binding to V3 (Cyc B peptide) was identified followed by examination of its 3D structure and dynamic behavior in the unbound status. To design the Cyc B peptide, the X-ray conformation for the identical site of the native protein was involved in the calculations as a starting model to find its best energy structural variant. The search for this most preferable structure was carried out by consecutive use of the molecular mechanics and simulated annealing methods. The molecular dynamics computations were implemented for the Cyc B peptide by the GROMACS computer package (http:// www.gromacs.org/). Results: The overmolecular structure of Cyc B with V3 was built by computer modeling tools and the immunophilinderived peptide able to mask effectively the structurally invariant V3 segments embracing the functionally crucial amino acids of the HIV-1 gp120 envelope protein was constructed and analyzed. Conclusions: Starting from the joint analysis of the results derived with those of the literature, the generated peptide was suggested to offer a promising basic structure for making a reality of the protein engineering projects aimed at developing the anti-AIDS drugs able to stop the HIV’s spread.
文摘在对软件构架和B/S应用程序体系结构的研究过程中,提出了如何运用构架和构件组装技术,通过对可复用构件的组装进行B/S应用程序的设计和快速开发。文章拟以C2构架风格作为在整合应用系统的业务逻辑的基础设施,以B/S Model 2作为表示层的框架原型,提出一种基于构架和构件的B/S结构模型,称为CB Model。并且介绍在研究过程中开发的组装支持工具BSAppBuilder。
