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
The modeling and optimization of wind farm layouts can effectively reduce the wake effect between turbine units,thereby enhancing the expected output power and avoiding negative influence.Traditional wind farm optimiz...The modeling and optimization of wind farm layouts can effectively reduce the wake effect between turbine units,thereby enhancing the expected output power and avoiding negative influence.Traditional wind farm optimization often uses idealized wake models,neglecting the influence of wind shear at different elevations,which leads to a lack of precision in estimating wake effects and fails to meet the accuracy and reliability requirements of practical engineering.To address this,we have constructed a three-dimensional 3D wind farm optimization model that incorporates elevation,utilizing a 3D wake model to better reflect real-world conditions.We aim to assess the optimization state of the algorithm and provide strong incentives at the right moments to ensure continuous evolution of the population.To this end,we propose an evolutionary adaptation degreeguided genetic algorithm based on power-law perturbation(PPGA)to adapt multidimensional conditions.We select the offshore wind power project in Nantong,Jiangsu,China,as a study example and compare PPGA with other well-performing algorithms under this practical project.Based on the actual wind condition data,the experimental results demonstrate that PPGA can effectively tackle this complex problem and achieve the best power efficiency.展开更多
In the big data era,robust solutions are obliged to be proposed to integrate and represent data from different formats and with different contents to assist the decision-making.Current cartographic and geographic info...In the big data era,robust solutions are obliged to be proposed to integrate and represent data from different formats and with different contents to assist the decision-making.Current cartographic and geographic information systems have limited capabilities for solving these problems.This paper describes an automatic and comprehensive system that conducts data fusion from all potentially related sources.In this system,a new Semantic Location Model(SemLM)is established to present the semantic concepts and location feature and demonstrate how locations are interrelated.In the SemLM,various types of location descriptors in different application scenarios can be analyzed and understood.Additionally,considering the challenges involved in data-intensive computation and visualization,this paper implements a Place-based Pan-Information System(P2S)as an innovative 4D system that dynamically associates and visualizes place-based information,using public security as the case study.展开更多
The high Ziz’s basin, which is part of the Central High Atlas, contains Jurassic superficial and deep aquifers. The information sheets are still fragmentary and insufficient because of the basin’s large size and its...The high Ziz’s basin, which is part of the Central High Atlas, contains Jurassic superficial and deep aquifers. The information sheets are still fragmentary and insufficient because of the basin’s large size and its complex geological structure. In order to improve the knowledge of these aquifers and the determination of the structure of aquifers, a 3D geological model was developed in this study. It was constructed from information provided by 200 mechanical soundings and 81 electrical surveys and geological maps. Compiled holes were analyzed, coded and integrated in the software Groundwater Modeling System 6.0 (GMS 6.0). For doing this, five lithostratigraphic units were considered: the Domerian, the Toarcian, the Aalenian, the Bajo-Bathonian and the Quaternary. The operation of the 3D stratigraphic model allowed making it closer to the geometry of Jurassic aquifers.展开更多
An experimental advanced superconducting tokamak （EAST） operation window with the lower hybrid current drive （LHCD） in H-mode is estimated by using a eore-SOL-divertor （C-S-D） model validated by the present EAST...An experimental advanced superconducting tokamak （EAST） operation window with the lower hybrid current drive （LHCD） in H-mode is estimated by using a eore-SOL-divertor （C-S-D） model validated by the present EAST divertor experiments. The operation window consists of four limits including two usual limits, one of which is the maximum allowable heat load onto the divertor plate, and two additional limits associated with the LHCD. The predictive EAST operation window is not qualified to fulfill its mission for high input power. To extend the operation window, gas puffing and impurity seeding are presented as two effective methods. In addition, the effect of the LHCD current on the operation window is also discussed. Our numerical analysis results provide a reference for the safe operation of EAST experiments with LHCD in future.展开更多
In this paper, we briefly go over the homogeneous 5D model field theory: from the 5D space-time inception, to its quantum field solutions given in terms of Higgs vacuum, filled with magnetic monopole bose fields of al...In this paper, we briefly go over the homogeneous 5D model field theory: from the 5D space-time inception, to its quantum field solutions given in terms of Higgs vacuum, filled with magnetic monopole bose fields of all energies. Then through the space dimension reduction projections, the Gell-Mann standard model was obtained as well as a quantum to Classical connection was made via introducing Bose distribution to the monopoles to obtain the Perelman entropy and Ricci Flow mappings. This provided us a picture to the creation of Astronomical objects, from galaxies to stars and planets. This method of splitting the monopole energy into ranges is extended to show that below the basic rest mass range of the electron and Quark, it still can be applied to explaining for the creation of the chemical elements periodic table. But perhaps the most interesting is in the lowest hundreds of Hz energy range, obtained from yet another 3 fold space symmetry breaking, into 2D × 1D, producing bio nitrogenous bases composed of 3 Carbon 12 in hexagon structures, due to preservation of the 1D monopole standing waves of this low frequencies. From that by imposing gauge changes the monopole states into DNA spectra. Since such spectra states retain the DLRO, it induces formation of charge carriers periodicity in a spherical bio cell.. It was then argued that due to cell’s surface proteins, the structure must contain partial filled VB, with “p” state hole density, and empty CB, separated from VB by a positive band gap. Such band structures resemble known HTC Cuprate ceramics. Since the HTC goes through a Superconductivity transition via the simultaneous bose exciton condensation, providing a Coulomb pressure, which reduces the band gap substantially, and induces the ODLRO transition of the hole density. The same obviously applies to the bio cells. Because of the near continuous exciton levels generated, a matching to the DNA spectra then can always occur by selective choices of proteins on the cell surface. Judging from a numerical study, we did years ago on YBCO, with doping. We found with a large enough VB hole density, the exciton induced superconducting gap can easily lead to <em>T</em><em>c</em> in the room temperature range. In fact by EMF excitation can increase the exciton pressure and trigger the ODLRO transition <em>T</em><em>c</em> upward. In fact, numerical results then suggest there do exist coherent EMF spectra from three key elements: Water, Carbon and Hydrogen, together with Oxygen, as studied over the years by numerous people, starting from Schr<span style="white-space:nowrap;">ö</span>dinger to most recently Geesink.展开更多
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partially supported by the Japan Society for the Promotion of Science(JSPS)KAKENHI(JP23K24899)Japan Science and Technology Agency(JST)Support for Pioneering Research Initiated by the Next Generation(SPRING)(JPMJSP2145).
文摘The modeling and optimization of wind farm layouts can effectively reduce the wake effect between turbine units,thereby enhancing the expected output power and avoiding negative influence.Traditional wind farm optimization often uses idealized wake models,neglecting the influence of wind shear at different elevations,which leads to a lack of precision in estimating wake effects and fails to meet the accuracy and reliability requirements of practical engineering.To address this,we have constructed a three-dimensional 3D wind farm optimization model that incorporates elevation,utilizing a 3D wake model to better reflect real-world conditions.We aim to assess the optimization state of the algorithm and provide strong incentives at the right moments to ensure continuous evolution of the population.To this end,we propose an evolutionary adaptation degreeguided genetic algorithm based on power-law perturbation(PPGA)to adapt multidimensional conditions.We select the offshore wind power project in Nantong,Jiangsu,China,as a study example and compare PPGA with other well-performing algorithms under this practical project.Based on the actual wind condition data,the experimental results demonstrate that PPGA can effectively tackle this complex problem and achieve the best power efficiency.
基金This work is supported by the National Natural Science Foundation of China(grant number 41301517,41271401,41329001,41401524,1416509,and 1535031)the National Key Research and Development Program(grant number 2016YFB0502204)+3 种基金the Fundamental Research Funds for the Central Universities(grant number 413000010)National Science and Technology Support Plan,the National Key Technology R&D Program(grant number 2012BAH35B03)Guangxi Natural Science Foundation(grant number 2015GXNSFBA139191)Scientific Project of Guangxi Education Department(grant number KY2015YB189).
文摘In the big data era,robust solutions are obliged to be proposed to integrate and represent data from different formats and with different contents to assist the decision-making.Current cartographic and geographic information systems have limited capabilities for solving these problems.This paper describes an automatic and comprehensive system that conducts data fusion from all potentially related sources.In this system,a new Semantic Location Model(SemLM)is established to present the semantic concepts and location feature and demonstrate how locations are interrelated.In the SemLM,various types of location descriptors in different application scenarios can be analyzed and understood.Additionally,considering the challenges involved in data-intensive computation and visualization,this paper implements a Place-based Pan-Information System(P2S)as an innovative 4D system that dynamically associates and visualizes place-based information,using public security as the case study.
文摘The high Ziz’s basin, which is part of the Central High Atlas, contains Jurassic superficial and deep aquifers. The information sheets are still fragmentary and insufficient because of the basin’s large size and its complex geological structure. In order to improve the knowledge of these aquifers and the determination of the structure of aquifers, a 3D geological model was developed in this study. It was constructed from information provided by 200 mechanical soundings and 81 electrical surveys and geological maps. Compiled holes were analyzed, coded and integrated in the software Groundwater Modeling System 6.0 (GMS 6.0). For doing this, five lithostratigraphic units were considered: the Domerian, the Toarcian, the Aalenian, the Bajo-Bathonian and the Quaternary. The operation of the 3D stratigraphic model allowed making it closer to the geometry of Jurassic aquifers.
基金supported by National Natural Science Foundation of China(Nos.11105176 and 11105224)
文摘An experimental advanced superconducting tokamak （EAST） operation window with the lower hybrid current drive （LHCD） in H-mode is estimated by using a eore-SOL-divertor （C-S-D） model validated by the present EAST divertor experiments. The operation window consists of four limits including two usual limits, one of which is the maximum allowable heat load onto the divertor plate, and two additional limits associated with the LHCD. The predictive EAST operation window is not qualified to fulfill its mission for high input power. To extend the operation window, gas puffing and impurity seeding are presented as two effective methods. In addition, the effect of the LHCD current on the operation window is also discussed. Our numerical analysis results provide a reference for the safe operation of EAST experiments with LHCD in future.
文摘In this paper, we briefly go over the homogeneous 5D model field theory: from the 5D space-time inception, to its quantum field solutions given in terms of Higgs vacuum, filled with magnetic monopole bose fields of all energies. Then through the space dimension reduction projections, the Gell-Mann standard model was obtained as well as a quantum to Classical connection was made via introducing Bose distribution to the monopoles to obtain the Perelman entropy and Ricci Flow mappings. This provided us a picture to the creation of Astronomical objects, from galaxies to stars and planets. This method of splitting the monopole energy into ranges is extended to show that below the basic rest mass range of the electron and Quark, it still can be applied to explaining for the creation of the chemical elements periodic table. But perhaps the most interesting is in the lowest hundreds of Hz energy range, obtained from yet another 3 fold space symmetry breaking, into 2D × 1D, producing bio nitrogenous bases composed of 3 Carbon 12 in hexagon structures, due to preservation of the 1D monopole standing waves of this low frequencies. From that by imposing gauge changes the monopole states into DNA spectra. Since such spectra states retain the DLRO, it induces formation of charge carriers periodicity in a spherical bio cell.. It was then argued that due to cell’s surface proteins, the structure must contain partial filled VB, with “p” state hole density, and empty CB, separated from VB by a positive band gap. Such band structures resemble known HTC Cuprate ceramics. Since the HTC goes through a Superconductivity transition via the simultaneous bose exciton condensation, providing a Coulomb pressure, which reduces the band gap substantially, and induces the ODLRO transition of the hole density. The same obviously applies to the bio cells. Because of the near continuous exciton levels generated, a matching to the DNA spectra then can always occur by selective choices of proteins on the cell surface. Judging from a numerical study, we did years ago on YBCO, with doping. We found with a large enough VB hole density, the exciton induced superconducting gap can easily lead to <em>T</em><em>c</em> in the room temperature range. In fact by EMF excitation can increase the exciton pressure and trigger the ODLRO transition <em>T</em><em>c</em> upward. In fact, numerical results then suggest there do exist coherent EMF spectra from three key elements: Water, Carbon and Hydrogen, together with Oxygen, as studied over the years by numerous people, starting from Schr<span style="white-space:nowrap;">ö</span>dinger to most recently Geesink.
