9-intersection model is the most popular framework used for formalizing the spatial relations between two spatial objectsA andB. It transforms the topological relationships between two simple spatial objectsA andB int...9-intersection model is the most popular framework used for formalizing the spatial relations between two spatial objectsA andB. It transforms the topological relationships between two simple spatial objectsA andB into point-set topology problem in terms of the intersections ofA’s boundary (?A), interior (A 0) and (A ?) withB’s boundary (?B), interior (B 0) and exterior (B ?). It is shown in this paper that there exist some limitations of the original 9-intersection model due to its definition of an object’s exterior as its complement, and it is difficult to distinguish different disjoint relations and relations between complex objects with holes, difficult or even impossible to compute the intersections with the two object’s complements (?A∩B ?,A 0∩?B ?,A ?∩?B,A ?∩B 0 andA ?∩B ?)since the complements are infinitive. The authors suggest to re-define the exterior of spatial object by replacing the complement with its Voronoi region. A new Voronoi-based 9-intersection (VNI) is proposed and used for formalizing topological relations between spatial bojects. By improving the 9-intersection model, it is now possible to distinguish disjoint relations and to deal with objects with holes. Also it is possible to compute the exterior-based intersections and manipulate spatial relations with the VNI.展开更多
Acetyltransferases,required to transfer an acetyl group on protein are highly conserved proteins that play a crucial role in development and disease.Protein acetylation is a common post-translational modification pivo...Acetyltransferases,required to transfer an acetyl group on protein are highly conserved proteins that play a crucial role in development and disease.Protein acetylation is a common post-translational modification pivotal to basic cellular processes.Close to 80%-90%of proteins are acetylated during translation,which is an irreversible process that affects protein structure,function,life,and localization.In this review,we have discussed the various N-acetyltransferases present in humans,their function,and how they might play a role in diseases.Furthermore,we have focused on N-acetyltransferase 9 and its role in microtubule stability.We have shed light on how N-acetyltransferase 9 and acetylation of proteins can potentially play a role in neurodegenerative diseases.We have specifically discussed the N-acetyltransferase 9-acetylation independent function and regulation of c-Jun N-terminal kinase signaling and microtubule stability during development and neurodegeneration.展开更多
[Objective]To construct an Escherichia coli mutant strain that accumulates pyruvate by genetic modification guided by the genome-scale metabolic network model.[Methods]Using a genome-scale metabolic network model as a...[Objective]To construct an Escherichia coli mutant strain that accumulates pyruvate by genetic modification guided by the genome-scale metabolic network model.[Methods]Using a genome-scale metabolic network model as a guide,we simulated pyruvate production of E.coli,screened key genes in metabolic pathways,and developed gene editing procedures accordingly.We knocked out the acetate kinase gene ackA,phosphate acetyltransferase gene pta,alcohol dehydrogenase adhE,glycogen synthase gene glgA,glycogen phosphorylase gene glgP,phosphoribosyl pyrophosphate(PRPP)synthase gene prs,ribose 1,5-bisphosphate phosphokinase gene phnN,and transporter encoding gene proP.Furthermore,we knocked in the transporter encoding gene ompC,flavonoid toxin gene fldA,and D-serine ammonia lyase gene dsdA.[Results]A shake flask process with the genetically edited mutant strain MG1655-6-2 under anaerobic conditions produced pyruvate at a titer of 10.46 g/L and a yield of 0.69 g/g.Metabolomic analysis revealed a significant increase in the pyruvate level in the fermentation broth,accompanied by notable decreases in the levels of certain related metabolic byproducts.Through 5 L fed-batch fermentation and an adaptive laboratory evolution,the strain finally achieved a pyruvate titer of 45.86 g/L.[Conclusion]This study illustrated the efficacy of a gene editing strategy predicted by a genome-scale metabolic network model in enhancing pyruvate accumulation in E.coli under anaerobic conditions and provided novel insights for microbial metabolic engineering.展开更多
目的评估血清基质金属蛋白酶-9(MMP-9)和乳酸脱氢酶(LDH)水平对重度子痫前期患者不良妊娠结局的预测价值,并探索二者联合模型的临床应用潜力。方法回顾性纳入2021年1月至2023年12月本院住院的96例重度子痫前期患者,根据妊娠结局分为非...目的评估血清基质金属蛋白酶-9(MMP-9)和乳酸脱氢酶(LDH)水平对重度子痫前期患者不良妊娠结局的预测价值,并探索二者联合模型的临床应用潜力。方法回顾性纳入2021年1月至2023年12月本院住院的96例重度子痫前期患者,根据妊娠结局分为非不良结局组(81例)与不良结局组(15例)。采用罗氏E170全自动电化学发光免疫分析仪检测血清LDH活性,应用R&D Systems MMP-9 ELISA Kit定量分析MMP-9水平。受试者工作曲线分析诊断价值,二元Logistic回归分析建立联合模型。结果非不良结局组MMP-9为349.56(252.24,410.16)ng/mL,显著高于不良结局组的227.23(201.38,255.69)ng/mL(P=0.001);而LDH水平在非不良结局组为304.60(257.40,365.40)U/L,显著低于不良结局组的407.10(350.20,517.20)U/L(P<0.001)。MMP-9的ROC曲线下面积(AUC)为0.79,阈值243.40ng/mL时灵敏度为66.67%、特异性为81.48%;LDH的AUC为0.80,阈值349.40U/L时灵敏度为80.00%、特异性为74.07%。二元Logistic回归构建的联合模型AUC达0.85,阈值0.138时灵敏度为93.33%、特异性为74.07%,其诊断效能显著优于单独指标(P=0.017和P=0.023)。结论MMP-9升高与LDH降低可作为SPE患者不良妊娠结局的独立预测标志物。二者联合模型通过协同效应显著提升诊断准确性,为临床早期干预提供了可靠依据。展开更多
This paper examines the performance of an atmospheric general circulation model (AGCM) developed at the State Key Laboratory of Numerical Modeling for Atmospheric Sciences and Geophysical Fluid Dynamics, Institute of ...This paper examines the performance of an atmospheric general circulation model (AGCM) developed at the State Key Laboratory of Numerical Modeling for Atmospheric Sciences and Geophysical Fluid Dynamics, Institute of Atmospheric Physics (LASG/IAP). It is a spectral model truncated at R42(2.8125°long×1.66°lat) resolution and with nine vertical levels, and referred to as R42L9/LASG hereafter. It is also the new version of atmospheric component model R15L9 of the global ocean-atmosphere-land system (GOALS/LASG). A 40-year simulation in which the model is forced with the climatological monthly mean sea surface temperature is compared with the 40-year (1958-97) U.S. National Center for Environmental Prediction (NGEP) global reanalysis and the 22-year (1979-2000) Xie-Arkin monthly precipitation climatology. The mean DJF and JJA geographical distributions of precipitation, sea level pressure, 500-hPa geopotential height, 850-hPa and 200-hPa zonal wind, and other fields averaged for the last 30-year integration of the R42L9 model are analyzed. Results show that the model reproduces well the observed basic patterns, particularly precipitation over the East Asian region. Comparing the new model with R15L9/LASG, the old version with coarse resolution (nearly 7.5°long×4.5°lat), shows an obvious improvement in the simulation of regional climate, especially precipitation. The weaknesses in simulation and future improvements of the model are also discussed.展开更多
Targeted genome editing technology has been widely used in biomedical studies. The CRISPR- associated RNA-guided endonuclease Cas9 has become a versatile genome editing tool. The CRISPR/Cas9 system is useful for study...Targeted genome editing technology has been widely used in biomedical studies. The CRISPR- associated RNA-guided endonuclease Cas9 has become a versatile genome editing tool. The CRISPR/Cas9 system is useful for studying gene function through efficient knock-out, knock-in or chromatin modification of the targeted gene loci in various cell types and organisms. It can be applied in a number of fields, such as genetic breeding, disease treatment and gene functional investigation In this review, we introduce the most recent developments and applications, the challenges, and future directions of Cas9 in generating disease animal model. Derived from the CRISPR adaptive immune system of bacteria, the development trend of Cas9 will inevitably fuel the vital applications from basic research to biotechnology and bio- medicine.展开更多
A new kinetic model for commercial unit of toluene disproportionation and C9-armatiocs transalkylation is developed based on the reported reaction scheme.A time based catalyst deactivation function taking weight hourl...A new kinetic model for commercial unit of toluene disproportionation and C9-armatiocs transalkylation is developed based on the reported reaction scheme.A time based catalyst deactivation function taking weight hourly space velocity(WHSV)into account is incorporated into the model,which reasonably accounts for the loss in activity because of coke deposition on the surface of catalyst during long-term operation.The kinetic parameters are benchmarked with several sets of balanced plant data and estimated by the differential variable metric optimiza- tion method.Sets of plant data at different operating conditions are applied to make sure validation of the model and the results show a good agreement between the model predictions and plant observations.The simulation analysis of key variables such as temperature and WHSV affecting process performance is discussed in detail,giv- ing the guidance to select suitable operating conditions.展开更多
Targeted genome editing is a continually evolving technology employing programmable nucleases to specifically change,insert,or remove a genomic sequence of interest.These advanced molecular tools include meganucleases...Targeted genome editing is a continually evolving technology employing programmable nucleases to specifically change,insert,or remove a genomic sequence of interest.These advanced molecular tools include meganucleases,zinc finger nucleases,transcription activator-like effector nucleases and RNA-guided engineered nucleases(RGENs),which create double-strand breaks at specific target sites in the genome,and repair DNA either by homologous recombination in the presence of donor DNA or via the error-prone non-homologous end-joining mechanism.A recently discovered group of RGENs known as CRISPR/Cas9 gene-editing systems allowed precise genome manipulation revealing a causal association between disease genotype and phenotype,without the need for the reengineering of the specific enzyme when targeting different sequences.CRISPR/Cas9 has been successfully employed as an ex vivo gene-editing tool in embryonic stem cells and patient-derived stem cells to understand pancreatic beta-cell development and function.RNA-guided nucleases also open the way for the generation of novel animal models for diabetes and allow testing the efficiency of various therapeutic approaches in diabetes,as summarized and exemplified in this manuscript.展开更多
A neurological abnormality called autism spectrum disorder(ASD)affects how a person perceives and interacts with others,leading to social interaction and communication issues.Limited and recurring behavioural patterns...A neurological abnormality called autism spectrum disorder(ASD)affects how a person perceives and interacts with others,leading to social interaction and communication issues.Limited and recurring behavioural patterns are another feature of the illness.Multiple mutations throughout development are the source of the neurodevelopmental disorder autism.However,a well-established model and perfect treatment for this spectrum disease has not been discovered.The rising era of the clustered regularly interspaced palindromic repeats(CRISPR)-associated protein 9(Cas9)system can streamline the complexity underlying the pathogenesis of ASD.The CRISPR-Cas9 system is a powerful genetic engineering tool used to edit the genome at the targeted site in a precise manner.The major hurdle in studying ASD is the lack of appropriate animal models presenting the complex symptoms of ASD.Therefore,CRISPR-Cas9 is being used worldwide to mimic the ASD-like pathology in various systems like in vitro cell lines,in vitro 3D organoid models and in vivo animal models.Apart from being used in establishing ASD models,CRISPR-Cas9 can also be used to treat the complexities of ASD.The aim of this review was to summarize and critically analyse the CRISPRCas9-mediated discoveries in the field of ASD.展开更多
The process of plane strain compression of 06Cr19Ni9NbN steel was carried out in the temperature range of 1000-1200℃ and the reduction ratio range of 10-50%.Combining the finite element numerical simulation,a new con...The process of plane strain compression of 06Cr19Ni9NbN steel was carried out in the temperature range of 1000-1200℃ and the reduction ratio range of 10-50%.Combining the finite element numerical simulation,a new constitutive model of thermal deformation was established, which provides the theoretical basis to optimize the plarie strain compression process of the steel.The temperature and grain size at different regions were achieved by experiment and simulation,respectively.According to the results,the mathematical models of stress and temperature during the plane strain compression were established by mathematical analysis method.The new temperature models were established in three regions,respectively,and the stress models took account of the variation of temperature and'st^rain rate.Finally,by comparing the results of calculation,numerical simulation and experiment,the accuracy and validity of these mathematical models were verified.展开更多
The availability of a well-characterized animal brain tumor model will play an important role in identifying treatments for human brain tumors. Wistar rats bearing 9L glioma cells can develop solid, well-circumcised t...The availability of a well-characterized animal brain tumor model will play an important role in identifying treatments for human brain tumors. Wistar rats bearing 9L glioma cells can develop solid, well-circumcised tumors, and may be a useful animal model for the evaluation of various therapeutic approaches for gliosarcomas. In this study, the 9L/Wistar rat glioma model was produced by intracerebral implantation of 9L^LUC glioma cells syngenic to Fischer 344 （F344） rats. Bioluminescence imaging showed that tumors progressively grew from day 7 to day 21 in 9L^LUC/F344 rats, and tumor regression was found in some 9L^LUC/Wistar rats. Hematoxylin-eosin staining verified that intracranial tumors were gliomas. Immunohistochemistry results demonstrated that no CD4- and CD8-positive cells were found in the syngeneic 9L^LUC/F344 model. However, many infiltrating CD4- and CD8-positive cells were observed within the tumors of the 9L^LUC/Wistar model. Our data suggests that compared with 9L/F344 rats, 9L glioma Wistar rats may not be suitable for evaluating brain glioma immunotherapies, even though the model induced an immune response and exhibited tumor regression.展开更多
Animal models are extensively used in all aspects of biomedical research,with substantial contributions to our understanding of diseases,the development of pharmaceuticals,and the exploration of gene functions.The fie...Animal models are extensively used in all aspects of biomedical research,with substantial contributions to our understanding of diseases,the development of pharmaceuticals,and the exploration of gene functions.The field of genome modification in rabbits has progressed slowly.However,recent advancements,particularly in CRISPR/Cas9-related technologies,have catalyzed the successful development of various genome-edited rabbit models to mimic diverse diseases,including cardiovascular disorders,immunodeficiencies,agingrelated ailments,neurological diseases,and ophthalmic pathologies.These models hold great promise in advancing biomedical research due to their closer physiological and biochemical resemblance to humans compared to mice.This review aims to summarize the novel gene-editing approaches currently available for rabbits and present the applications and prospects of such models in biomedicine,underscoring their impact and future potential in translational medicine.展开更多
In the lower parts of oil reservoirs Chang 9 and Chang 10 of the Yanchang Formation are oil-bearing layers newly found in oil exploration in the Ordos Basin.Based on GC,GC-MS analyses of saturated hydrocarbons from cr...In the lower parts of oil reservoirs Chang 9 and Chang 10 of the Yanchang Formation are oil-bearing layers newly found in oil exploration in the Ordos Basin.Based on GC,GC-MS analyses of saturated hydrocarbons from crude oils and source rocks,reservoir fluid inclusions and BasinMod,the origin of crude oils,accumulation period and accumulation models are discussed in combination with other petroleum geology data in this paper.The result shows that(1) there are two different types of crude oils in oil reservoir Chang 9 in the Longdong and Jiyuan regions:crude oils of typeⅠ(Well D86,Well A44,Well A75,Well B227,Well X62 and Well Z150) are mainly de-rived from the Chang 7 source rocks(including mudstones and shales) and distributed in the Jiyuan and Longdong regions;those of typeⅡ(Well Z14 and Well Y427),are distributed in the Longdong region,which are derived from the Chang 9 source rocks.Crude oils from oil reservoir Chang 10 in the Shanbei region are mainly derived from the Chang-9 source rocks;(2) there are two phases of hydrocarbon filling in oil reservoir Chang 9 in the Jiyuan and Longdong regions and oil reservoir Chang 10 in the Shanbei region:The first phase started at the early stage of J2z.The process of hydrocarbon filling was discontinuous in the Late Jurassic,because of the tectonic-thermal event in the Ordos Basin.The second phase was the main accumulation period,and hydrocarbons began to accumulate from the late stage of J2a to the middle-late of K1,mainly at the middle-late stage of K1;(3) there exist two types of accu-mulation models in oil reservoirs Chang 9 and Chang 10 of the Yanchang Formation:source rocks of the reservoirs in oil reservoir Chang 9 in the Jiyuan region and oil reservoir Chang 10 in the Shanbei region,the mixed type of reservoirs on the lateral side of source rocks and source rocks of the reservoirs in oil reservoir Chang 9 in the Long-dong region.展开更多
In order to research the hot deformation behavior of 9CrMoCoB heat-resistant steel,hot compression tests were performed over a wide range of temperatures from 850 to 1150℃ and strain rates from 0.01 to 10.00 s^-1.The...In order to research the hot deformation behavior of 9CrMoCoB heat-resistant steel,hot compression tests were performed over a wide range of temperatures from 850 to 1150℃ and strain rates from 0.01 to 10.00 s^-1.The flow stress appears to increase with the decrease in deformation temperature and the increase in strain rate.The relationship between microstructural evolution and deformation parameters was studied,indicating that both low strain rate and high deformation temperature appear to promote the dynamic recrystallization,while excessively high temperature with low strain rate would result in the high non-uniformity of grain size.The experimental stress-strain data was applied to calculate the material constants involved in the Arrhenius-type constitutive model and the modified Zerilli-Armstrong(MZA)model,and feasibility of these two models was evaluated.The results show that the MZA model is more accurate to predict the high-temperature flow behavior of the experimental steel than the Arrhenius-type constitutive equation.展开更多
基金Project supported by the National Natural Science Foundation of China(No.49471059)
文摘9-intersection model is the most popular framework used for formalizing the spatial relations between two spatial objectsA andB. It transforms the topological relationships between two simple spatial objectsA andB into point-set topology problem in terms of the intersections ofA’s boundary (?A), interior (A 0) and (A ?) withB’s boundary (?B), interior (B 0) and exterior (B ?). It is shown in this paper that there exist some limitations of the original 9-intersection model due to its definition of an object’s exterior as its complement, and it is difficult to distinguish different disjoint relations and relations between complex objects with holes, difficult or even impossible to compute the intersections with the two object’s complements (?A∩B ?,A 0∩?B ?,A ?∩?B,A ?∩B 0 andA ?∩B ?)since the complements are infinitive. The authors suggest to re-define the exterior of spatial object by replacing the complement with its Voronoi region. A new Voronoi-based 9-intersection (VNI) is proposed and used for formalizing topological relations between spatial bojects. By improving the 9-intersection model, it is now possible to distinguish disjoint relations and to deal with objects with holes. Also it is possible to compute the exterior-based intersections and manipulate spatial relations with the VNI.
基金supported by 1RO1EY032959-01 and RO1 supplement from NIH,Schuellein Chair Endowment Fund and STEM Catalyst Grant from the University of Dayton(to AS).
文摘Acetyltransferases,required to transfer an acetyl group on protein are highly conserved proteins that play a crucial role in development and disease.Protein acetylation is a common post-translational modification pivotal to basic cellular processes.Close to 80%-90%of proteins are acetylated during translation,which is an irreversible process that affects protein structure,function,life,and localization.In this review,we have discussed the various N-acetyltransferases present in humans,their function,and how they might play a role in diseases.Furthermore,we have focused on N-acetyltransferase 9 and its role in microtubule stability.We have shed light on how N-acetyltransferase 9 and acetylation of proteins can potentially play a role in neurodegenerative diseases.We have specifically discussed the N-acetyltransferase 9-acetylation independent function and regulation of c-Jun N-terminal kinase signaling and microtubule stability during development and neurodegeneration.
基金supported by the Hebei Provincial Key Research and Development Project(21372803D)。
文摘[Objective]To construct an Escherichia coli mutant strain that accumulates pyruvate by genetic modification guided by the genome-scale metabolic network model.[Methods]Using a genome-scale metabolic network model as a guide,we simulated pyruvate production of E.coli,screened key genes in metabolic pathways,and developed gene editing procedures accordingly.We knocked out the acetate kinase gene ackA,phosphate acetyltransferase gene pta,alcohol dehydrogenase adhE,glycogen synthase gene glgA,glycogen phosphorylase gene glgP,phosphoribosyl pyrophosphate(PRPP)synthase gene prs,ribose 1,5-bisphosphate phosphokinase gene phnN,and transporter encoding gene proP.Furthermore,we knocked in the transporter encoding gene ompC,flavonoid toxin gene fldA,and D-serine ammonia lyase gene dsdA.[Results]A shake flask process with the genetically edited mutant strain MG1655-6-2 under anaerobic conditions produced pyruvate at a titer of 10.46 g/L and a yield of 0.69 g/g.Metabolomic analysis revealed a significant increase in the pyruvate level in the fermentation broth,accompanied by notable decreases in the levels of certain related metabolic byproducts.Through 5 L fed-batch fermentation and an adaptive laboratory evolution,the strain finally achieved a pyruvate titer of 45.86 g/L.[Conclusion]This study illustrated the efficacy of a gene editing strategy predicted by a genome-scale metabolic network model in enhancing pyruvate accumulation in E.coli under anaerobic conditions and provided novel insights for microbial metabolic engineering.
文摘目的评估血清基质金属蛋白酶-9(MMP-9)和乳酸脱氢酶(LDH)水平对重度子痫前期患者不良妊娠结局的预测价值,并探索二者联合模型的临床应用潜力。方法回顾性纳入2021年1月至2023年12月本院住院的96例重度子痫前期患者,根据妊娠结局分为非不良结局组(81例)与不良结局组(15例)。采用罗氏E170全自动电化学发光免疫分析仪检测血清LDH活性,应用R&D Systems MMP-9 ELISA Kit定量分析MMP-9水平。受试者工作曲线分析诊断价值,二元Logistic回归分析建立联合模型。结果非不良结局组MMP-9为349.56(252.24,410.16)ng/mL,显著高于不良结局组的227.23(201.38,255.69)ng/mL(P=0.001);而LDH水平在非不良结局组为304.60(257.40,365.40)U/L,显著低于不良结局组的407.10(350.20,517.20)U/L(P<0.001)。MMP-9的ROC曲线下面积(AUC)为0.79,阈值243.40ng/mL时灵敏度为66.67%、特异性为81.48%;LDH的AUC为0.80,阈值349.40U/L时灵敏度为80.00%、特异性为74.07%。二元Logistic回归构建的联合模型AUC达0.85,阈值0.138时灵敏度为93.33%、特异性为74.07%,其诊断效能显著优于单独指标(P=0.017和P=0.023)。结论MMP-9升高与LDH降低可作为SPE患者不良妊娠结局的独立预测标志物。二者联合模型通过协同效应显著提升诊断准确性,为临床早期干预提供了可靠依据。
文摘This paper examines the performance of an atmospheric general circulation model (AGCM) developed at the State Key Laboratory of Numerical Modeling for Atmospheric Sciences and Geophysical Fluid Dynamics, Institute of Atmospheric Physics (LASG/IAP). It is a spectral model truncated at R42(2.8125°long×1.66°lat) resolution and with nine vertical levels, and referred to as R42L9/LASG hereafter. It is also the new version of atmospheric component model R15L9 of the global ocean-atmosphere-land system (GOALS/LASG). A 40-year simulation in which the model is forced with the climatological monthly mean sea surface temperature is compared with the 40-year (1958-97) U.S. National Center for Environmental Prediction (NGEP) global reanalysis and the 22-year (1979-2000) Xie-Arkin monthly precipitation climatology. The mean DJF and JJA geographical distributions of precipitation, sea level pressure, 500-hPa geopotential height, 850-hPa and 200-hPa zonal wind, and other fields averaged for the last 30-year integration of the R42L9 model are analyzed. Results show that the model reproduces well the observed basic patterns, particularly precipitation over the East Asian region. Comparing the new model with R15L9/LASG, the old version with coarse resolution (nearly 7.5°long×4.5°lat), shows an obvious improvement in the simulation of regional climate, especially precipitation. The weaknesses in simulation and future improvements of the model are also discussed.
基金partially supported by the National Natural Science Foundation of China(81202110,81120108019,U1132605 and 81325016)
文摘Targeted genome editing technology has been widely used in biomedical studies. The CRISPR- associated RNA-guided endonuclease Cas9 has become a versatile genome editing tool. The CRISPR/Cas9 system is useful for studying gene function through efficient knock-out, knock-in or chromatin modification of the targeted gene loci in various cell types and organisms. It can be applied in a number of fields, such as genetic breeding, disease treatment and gene functional investigation In this review, we introduce the most recent developments and applications, the challenges, and future directions of Cas9 in generating disease animal model. Derived from the CRISPR adaptive immune system of bacteria, the development trend of Cas9 will inevitably fuel the vital applications from basic research to biotechnology and bio- medicine.
基金Supported by the National＇Creative Research Groups Science Foundation of China （No.60421002） and priority supported financially by ＂the New Century 151 Talent Project＂ of Zhejiang Province.
文摘A new kinetic model for commercial unit of toluene disproportionation and C9-armatiocs transalkylation is developed based on the reported reaction scheme.A time based catalyst deactivation function taking weight hourly space velocity(WHSV)into account is incorporated into the model,which reasonably accounts for the loss in activity because of coke deposition on the surface of catalyst during long-term operation.The kinetic parameters are benchmarked with several sets of balanced plant data and estimated by the differential variable metric optimiza- tion method.Sets of plant data at different operating conditions are applied to make sure validation of the model and the results show a good agreement between the model predictions and plant observations.The simulation analysis of key variables such as temperature and WHSV affecting process performance is discussed in detail,giv- ing the guidance to select suitable operating conditions.
基金the Akdeniz University Scientific Research Commission and the Scientific and Technological Research Council of Turkey,No.TUBITAK-215S820.
文摘Targeted genome editing is a continually evolving technology employing programmable nucleases to specifically change,insert,or remove a genomic sequence of interest.These advanced molecular tools include meganucleases,zinc finger nucleases,transcription activator-like effector nucleases and RNA-guided engineered nucleases(RGENs),which create double-strand breaks at specific target sites in the genome,and repair DNA either by homologous recombination in the presence of donor DNA or via the error-prone non-homologous end-joining mechanism.A recently discovered group of RGENs known as CRISPR/Cas9 gene-editing systems allowed precise genome manipulation revealing a causal association between disease genotype and phenotype,without the need for the reengineering of the specific enzyme when targeting different sequences.CRISPR/Cas9 has been successfully employed as an ex vivo gene-editing tool in embryonic stem cells and patient-derived stem cells to understand pancreatic beta-cell development and function.RNA-guided nucleases also open the way for the generation of novel animal models for diabetes and allow testing the efficiency of various therapeutic approaches in diabetes,as summarized and exemplified in this manuscript.
文摘A neurological abnormality called autism spectrum disorder(ASD)affects how a person perceives and interacts with others,leading to social interaction and communication issues.Limited and recurring behavioural patterns are another feature of the illness.Multiple mutations throughout development are the source of the neurodevelopmental disorder autism.However,a well-established model and perfect treatment for this spectrum disease has not been discovered.The rising era of the clustered regularly interspaced palindromic repeats(CRISPR)-associated protein 9(Cas9)system can streamline the complexity underlying the pathogenesis of ASD.The CRISPR-Cas9 system is a powerful genetic engineering tool used to edit the genome at the targeted site in a precise manner.The major hurdle in studying ASD is the lack of appropriate animal models presenting the complex symptoms of ASD.Therefore,CRISPR-Cas9 is being used worldwide to mimic the ASD-like pathology in various systems like in vitro cell lines,in vitro 3D organoid models and in vivo animal models.Apart from being used in establishing ASD models,CRISPR-Cas9 can also be used to treat the complexities of ASD.The aim of this review was to summarize and critically analyse the CRISPRCas9-mediated discoveries in the field of ASD.
基金National Natural Science Foundation of China (51275330,51775361)Natural Science Foundation of Shanxi Province (2014011015-5).
文摘The process of plane strain compression of 06Cr19Ni9NbN steel was carried out in the temperature range of 1000-1200℃ and the reduction ratio range of 10-50%.Combining the finite element numerical simulation,a new constitutive model of thermal deformation was established, which provides the theoretical basis to optimize the plarie strain compression process of the steel.The temperature and grain size at different regions were achieved by experiment and simulation,respectively.According to the results,the mathematical models of stress and temperature during the plane strain compression were established by mathematical analysis method.The new temperature models were established in three regions,respectively,and the stress models took account of the variation of temperature and'st^rain rate.Finally,by comparing the results of calculation,numerical simulation and experiment,the accuracy and validity of these mathematical models were verified.
文摘The availability of a well-characterized animal brain tumor model will play an important role in identifying treatments for human brain tumors. Wistar rats bearing 9L glioma cells can develop solid, well-circumcised tumors, and may be a useful animal model for the evaluation of various therapeutic approaches for gliosarcomas. In this study, the 9L/Wistar rat glioma model was produced by intracerebral implantation of 9L^LUC glioma cells syngenic to Fischer 344 （F344） rats. Bioluminescence imaging showed that tumors progressively grew from day 7 to day 21 in 9L^LUC/F344 rats, and tumor regression was found in some 9L^LUC/Wistar rats. Hematoxylin-eosin staining verified that intracranial tumors were gliomas. Immunohistochemistry results demonstrated that no CD4- and CD8-positive cells were found in the syngeneic 9L^LUC/F344 model. However, many infiltrating CD4- and CD8-positive cells were observed within the tumors of the 9L^LUC/Wistar model. Our data suggests that compared with 9L/F344 rats, 9L glioma Wistar rats may not be suitable for evaluating brain glioma immunotherapies, even though the model induced an immune response and exhibited tumor regression.
基金supported by the National Natural Science Foundation of China (31970574)。
文摘Animal models are extensively used in all aspects of biomedical research,with substantial contributions to our understanding of diseases,the development of pharmaceuticals,and the exploration of gene functions.The field of genome modification in rabbits has progressed slowly.However,recent advancements,particularly in CRISPR/Cas9-related technologies,have catalyzed the successful development of various genome-edited rabbit models to mimic diverse diseases,including cardiovascular disorders,immunodeficiencies,agingrelated ailments,neurological diseases,and ophthalmic pathologies.These models hold great promise in advancing biomedical research due to their closer physiological and biochemical resemblance to humans compared to mice.This review aims to summarize the novel gene-editing approaches currently available for rabbits and present the applications and prospects of such models in biomedicine,underscoring their impact and future potential in translational medicine.
文摘In the lower parts of oil reservoirs Chang 9 and Chang 10 of the Yanchang Formation are oil-bearing layers newly found in oil exploration in the Ordos Basin.Based on GC,GC-MS analyses of saturated hydrocarbons from crude oils and source rocks,reservoir fluid inclusions and BasinMod,the origin of crude oils,accumulation period and accumulation models are discussed in combination with other petroleum geology data in this paper.The result shows that(1) there are two different types of crude oils in oil reservoir Chang 9 in the Longdong and Jiyuan regions:crude oils of typeⅠ(Well D86,Well A44,Well A75,Well B227,Well X62 and Well Z150) are mainly de-rived from the Chang 7 source rocks(including mudstones and shales) and distributed in the Jiyuan and Longdong regions;those of typeⅡ(Well Z14 and Well Y427),are distributed in the Longdong region,which are derived from the Chang 9 source rocks.Crude oils from oil reservoir Chang 10 in the Shanbei region are mainly derived from the Chang-9 source rocks;(2) there are two phases of hydrocarbon filling in oil reservoir Chang 9 in the Jiyuan and Longdong regions and oil reservoir Chang 10 in the Shanbei region:The first phase started at the early stage of J2z.The process of hydrocarbon filling was discontinuous in the Late Jurassic,because of the tectonic-thermal event in the Ordos Basin.The second phase was the main accumulation period,and hydrocarbons began to accumulate from the late stage of J2a to the middle-late of K1,mainly at the middle-late stage of K1;(3) there exist two types of accu-mulation models in oil reservoirs Chang 9 and Chang 10 of the Yanchang Formation:source rocks of the reservoirs in oil reservoir Chang 9 in the Jiyuan region and oil reservoir Chang 10 in the Shanbei region,the mixed type of reservoirs on the lateral side of source rocks and source rocks of the reservoirs in oil reservoir Chang 9 in the Long-dong region.
基金The authors are grateful to the National Natural Science Foundation of China(Granted Nos.51474156 and U1660201)the National Magnetic Confinement Fusion Energy Research Project(Granted No.2015GB119001)for grant and financial support.
文摘In order to research the hot deformation behavior of 9CrMoCoB heat-resistant steel,hot compression tests were performed over a wide range of temperatures from 850 to 1150℃ and strain rates from 0.01 to 10.00 s^-1.The flow stress appears to increase with the decrease in deformation temperature and the increase in strain rate.The relationship between microstructural evolution and deformation parameters was studied,indicating that both low strain rate and high deformation temperature appear to promote the dynamic recrystallization,while excessively high temperature with low strain rate would result in the high non-uniformity of grain size.The experimental stress-strain data was applied to calculate the material constants involved in the Arrhenius-type constitutive model and the modified Zerilli-Armstrong(MZA)model,and feasibility of these two models was evaluated.The results show that the MZA model is more accurate to predict the high-temperature flow behavior of the experimental steel than the Arrhenius-type constitutive equation.
