Apolipoprotein E has diverse functions in neurons:Apolipoprotein E(ApoE)is a glycoprotein that primarily regulates lipid metabolism and transport in the central nervous system.There are three predominant human ApoE pr...Apolipoprotein E has diverse functions in neurons:Apolipoprotein E(ApoE)is a glycoprotein that primarily regulates lipid metabolism and transport in the central nervous system.There are three predominant human ApoE protein isoforms with cysteine and arginine substitutions at amino acid positions 112 and 158 that impact their lipidation and related functions(Flowers and Rebeck,2020).ApoE2 is characterized by Cys112 and Cys158,ApoE3 by Cys112 and Arg158,whereas ApoE4 contains Arg112 and Arg158.展开更多
Maintainability influencing attributes are analyzed, their weight and value calculating methods are given, and the maintainability fuzzy evaluation method is proposed based on the relative closeness. According to the ...Maintainability influencing attributes are analyzed, their weight and value calculating methods are given, and the maintainability fuzzy evaluation method is proposed based on the relative closeness. According to the maintenance task simulation operated in virtual environment, the maintainability virtual evaluation model is built by analyzing the maintenance task for each replaceable unit of product. At last, a case study is given based upon the main landing gear system of a certain type civil aircraft, and the result indicates that the model is suitable for maintainability qualitative evaluation and can support maintainability concurrent design.展开更多
This paper uses three size metrics,which are collectable during the design phase,to analyze the potentially confounding effect of class size on the associations between object-oriented（OO）metrics and maintainability...This paper uses three size metrics,which are collectable during the design phase,to analyze the potentially confounding effect of class size on the associations between object-oriented（OO）metrics and maintainability.To draw as many general conclusions as possible,the confounding effect of class size is analyzed on 127 C＋＋ systems and 113 Java systems.For each OO metric,the indirect effect that represents the distortion of the association caused by class size and its variance for individual systems is first computed.Then,a statistical meta-analysis technique is used to compute the average indirect effect over all the systems and to determine if it is significantly different from zero.The experimental results show that the confounding effects of class size on the associations between OO metrics and maintainability generally exist,regardless of whatever size metric is used.Therefore,empirical studies validating OO metrics on maintainability should consider class size as a confounding variable.展开更多
Traditional mining in open pit mines often uses explosives,leading to environmental hazards,with flyrock being a critical issue.In detail,excess flying rock beyond the designated explosion area was identified as the p...Traditional mining in open pit mines often uses explosives,leading to environmental hazards,with flyrock being a critical issue.In detail,excess flying rock beyond the designated explosion area was identified as the primary cause of fatal and non-fatal blasting hazards in open pit mining.Therefore,the accurate and reliable prediction of flyrock becomes crucial for effectively managing and mitigating associated problems.This study used the Light Gradient Boosting Machine(LightGBM)model to predict flyrock in a lead-zinc mine,with promising results.To improve its accuracy,multi-verse optimizer(MVO)and ant lion optimizer(ALO)metaheuristic algorithms were introduced.Results showed MVO-LightGBM outperformed conventional LightGBM.Additionally,decision tree(DT),support vector machine(SVM),and classification and regression tree(CART)models were trained and compared with MVO-LightGBM.The MVO-LightGBM model excelled over DT,SVM,and CART.This study highlights MVO-LightGBM's effectiveness and potential for broader applications.Furthermore,a multiple parametric sensitivity analysis(MPSA)algorithm was employed to specify the sensitivity of parameters.MPSA results indicated that the highest and lowest sensitivities are relevant to blasted rock per hole and spacing with theγ=1752.12 andγ=49.52,respectively.展开更多
Tooth morphogenesis is orchestrated by a complex interplay of signaling pathways and transcription factors that control cell proliferation,apoptosis,and differentiation,with the Wnt/β-catenin signaling pathway playin...Tooth morphogenesis is orchestrated by a complex interplay of signaling pathways and transcription factors that control cell proliferation,apoptosis,and differentiation,with the Wnt/β-catenin signaling pathway playing a pivotal role.However,the comprehensive regulatory mechanisms of Wnt/β-catenin signaling remain largely unclear.Smad7,a key antagonist of the TGF-βsuperfamily,is essential for maintaining tissue homeostasis and ensuring proper cellular function.Our previous study has demonstrated that Smad7 knockout in mice leads to impaired proliferative property of tooth germ cells,resulting in small molars.Here,we identified SMAD7 expression in human dental papilla and dental pulp,colocalized with β-CATENIN and cell proliferationrelated proteins.RNA sequencing analysis revealed a significant reduction in Wnt signaling activity in Smad7-deficient mouse tooth germs.Using lentivirus transfection,we established SMAD7-knockdown human dental papilla stem cells,which manifested remarkably blunt proliferation rate,along with diminished Wnt signaling activity.In vivo transplantation investigations further revealed the indispensable role of SMAD7 in dentin formation.Mechanistically,we revealed that β-CATENIN interacts with P-SMAD2/3 and SMAD7 through co-immunoprecipitation and yeast two-hybrid assays.Inhibition of TGF-β pathway or disruption of SMAD7/β-CATENIN transcription factor complex formation potently impacted Wnt/β-catenin activities,indicating both direct and indirect regulatory mechanisms.These findings highlight the critical role of SMAD7 in the proliferation and diffe rentiation of human dental stem cells,which could contribute to dental tissue regeneration and engineering.展开更多
Microglia cells are the resident innate immune cells of the central nervous system(CNS)(Paolicelli et al.,2022).They play a pivotal role in CNS development and in maintaining homeostasis during adulthood.Microglia are...Microglia cells are the resident innate immune cells of the central nervous system(CNS)(Paolicelli et al.,2022).They play a pivotal role in CNS development and in maintaining homeostasis during adulthood.Microglia are being extensively studied for their involvement in CNS disorders,ranging from autoimmune diseases such as multiple sclerosis to neurodegenerative and psychiatric conditions,as well as stroke and brain tumors(Paolicelli et al.,2022).展开更多
The rise of the aging population parallels the rapidly increasing cases of neurological disorders. This puts pressure on scientists and physicians to find novel methods that can prevent and treat neurodegeneration. Th...The rise of the aging population parallels the rapidly increasing cases of neurological disorders. This puts pressure on scientists and physicians to find novel methods that can prevent and treat neurodegeneration. The brain is made up of a complex network of different cell types that work in tandem to maintain systemic homeostasis.展开更多
Dendritic spines are small protrusions along dendrites that contain most of the excitatory synapses in principal neurons,playing a crucial role in neuronal function by creating a compartmentalized environment for sign...Dendritic spines are small protrusions along dendrites that contain most of the excitatory synapses in principal neurons,playing a crucial role in neuronal function by creating a compartmentalized environment for signal transduction.The plasticity of spine morphologies provides a tunable handle to regulate calcium signal dynamics,allowing rapid regulation of protein expression necessary to establish and maintain synapses(Cornejo et al.,2022).If excitatory inputs were to be located primarily on dendritic shafts,dendrites would frequently short-circuit,preventing voltage signals from propagating(Cornejo et al.,2022).It is thus not surprising that the structural plasticity of dendritic spines is closely linked to synaptic plasticity and memory formation(Berry and Nedivi,2017).While comprehensive in vitro studies have been conducted,in vivo studies that directly tackle the mechanism of dendritic transport and translation in regulating spine plasticity spatiotemporally are limited.展开更多
基金supported by core funding provided by Temasek Life Sciences Laboratory(to CTO)。
文摘Apolipoprotein E has diverse functions in neurons:Apolipoprotein E(ApoE)is a glycoprotein that primarily regulates lipid metabolism and transport in the central nervous system.There are three predominant human ApoE protein isoforms with cysteine and arginine substitutions at amino acid positions 112 and 158 that impact their lipidation and related functions(Flowers and Rebeck,2020).ApoE2 is characterized by Cys112 and Cys158,ApoE3 by Cys112 and Arg158,whereas ApoE4 contains Arg112 and Arg158.
基金National Natural Science Foundation of China-Joint Found of Civil Aviation Research (60572171)
文摘Maintainability influencing attributes are analyzed, their weight and value calculating methods are given, and the maintainability fuzzy evaluation method is proposed based on the relative closeness. According to the maintenance task simulation operated in virtual environment, the maintainability virtual evaluation model is built by analyzing the maintenance task for each replaceable unit of product. At last, a case study is given based upon the main landing gear system of a certain type civil aircraft, and the result indicates that the model is suitable for maintainability qualitative evaluation and can support maintainability concurrent design.
基金The National Natural Science Foundation of China(No.60425206,60633010)
文摘This paper uses three size metrics,which are collectable during the design phase,to analyze the potentially confounding effect of class size on the associations between object-oriented（OO）metrics and maintainability.To draw as many general conclusions as possible,the confounding effect of class size is analyzed on 127 C＋＋ systems and 113 Java systems.For each OO metric,the indirect effect that represents the distortion of the association caused by class size and its variance for individual systems is first computed.Then,a statistical meta-analysis technique is used to compute the average indirect effect over all the systems and to determine if it is significantly different from zero.The experimental results show that the confounding effects of class size on the associations between OO metrics and maintainability generally exist,regardless of whatever size metric is used.Therefore,empirical studies validating OO metrics on maintainability should consider class size as a confounding variable.
基金funded by the Key Laboratory of Geological Safety of Coastal Urban Underground Space,Ministry of Natural Resources of China(Grant No.BHKF2022Y02)Natural Science Foundation of Guangdong Province,China(Grant No.2024A1515011162)Natural Science Foundation of Shandong Province,China(Grant No.ZR2024QE021).
文摘Traditional mining in open pit mines often uses explosives,leading to environmental hazards,with flyrock being a critical issue.In detail,excess flying rock beyond the designated explosion area was identified as the primary cause of fatal and non-fatal blasting hazards in open pit mining.Therefore,the accurate and reliable prediction of flyrock becomes crucial for effectively managing and mitigating associated problems.This study used the Light Gradient Boosting Machine(LightGBM)model to predict flyrock in a lead-zinc mine,with promising results.To improve its accuracy,multi-verse optimizer(MVO)and ant lion optimizer(ALO)metaheuristic algorithms were introduced.Results showed MVO-LightGBM outperformed conventional LightGBM.Additionally,decision tree(DT),support vector machine(SVM),and classification and regression tree(CART)models were trained and compared with MVO-LightGBM.The MVO-LightGBM model excelled over DT,SVM,and CART.This study highlights MVO-LightGBM's effectiveness and potential for broader applications.Furthermore,a multiple parametric sensitivity analysis(MPSA)algorithm was employed to specify the sensitivity of parameters.MPSA results indicated that the highest and lowest sensitivities are relevant to blasted rock per hole and spacing with theγ=1752.12 andγ=49.52,respectively.
基金supported by the National Key Research and Development Program of China to W.Tian (2022YFA1104400)the National Natural Science Foundation of China to T.Chen (82100959)a grant from the Sichuan Science and Technology Program to Z.Liu (2024YFFK0068)。
文摘Tooth morphogenesis is orchestrated by a complex interplay of signaling pathways and transcription factors that control cell proliferation,apoptosis,and differentiation,with the Wnt/β-catenin signaling pathway playing a pivotal role.However,the comprehensive regulatory mechanisms of Wnt/β-catenin signaling remain largely unclear.Smad7,a key antagonist of the TGF-βsuperfamily,is essential for maintaining tissue homeostasis and ensuring proper cellular function.Our previous study has demonstrated that Smad7 knockout in mice leads to impaired proliferative property of tooth germ cells,resulting in small molars.Here,we identified SMAD7 expression in human dental papilla and dental pulp,colocalized with β-CATENIN and cell proliferationrelated proteins.RNA sequencing analysis revealed a significant reduction in Wnt signaling activity in Smad7-deficient mouse tooth germs.Using lentivirus transfection,we established SMAD7-knockdown human dental papilla stem cells,which manifested remarkably blunt proliferation rate,along with diminished Wnt signaling activity.In vivo transplantation investigations further revealed the indispensable role of SMAD7 in dentin formation.Mechanistically,we revealed that β-CATENIN interacts with P-SMAD2/3 and SMAD7 through co-immunoprecipitation and yeast two-hybrid assays.Inhibition of TGF-β pathway or disruption of SMAD7/β-CATENIN transcription factor complex formation potently impacted Wnt/β-catenin activities,indicating both direct and indirect regulatory mechanisms.These findings highlight the critical role of SMAD7 in the proliferation and diffe rentiation of human dental stem cells,which could contribute to dental tissue regeneration and engineering.
文摘Microglia cells are the resident innate immune cells of the central nervous system(CNS)(Paolicelli et al.,2022).They play a pivotal role in CNS development and in maintaining homeostasis during adulthood.Microglia are being extensively studied for their involvement in CNS disorders,ranging from autoimmune diseases such as multiple sclerosis to neurodegenerative and psychiatric conditions,as well as stroke and brain tumors(Paolicelli et al.,2022).
文摘The rise of the aging population parallels the rapidly increasing cases of neurological disorders. This puts pressure on scientists and physicians to find novel methods that can prevent and treat neurodegeneration. The brain is made up of a complex network of different cell types that work in tandem to maintain systemic homeostasis.
基金supported by the National Natural Science Foundation of China(NSFC/RGC/JRF N_HKU735/21)Research Grant Council of Hong Kong,China(17102120,17108821,17103922,C1024-22GF,C7074-21G)+1 种基金Health and Medical Research Fund(HMRF 09200966)(to CSWL)FRQS Postdoctoral Fellowship(to AHKF).
文摘Dendritic spines are small protrusions along dendrites that contain most of the excitatory synapses in principal neurons,playing a crucial role in neuronal function by creating a compartmentalized environment for signal transduction.The plasticity of spine morphologies provides a tunable handle to regulate calcium signal dynamics,allowing rapid regulation of protein expression necessary to establish and maintain synapses(Cornejo et al.,2022).If excitatory inputs were to be located primarily on dendritic shafts,dendrites would frequently short-circuit,preventing voltage signals from propagating(Cornejo et al.,2022).It is thus not surprising that the structural plasticity of dendritic spines is closely linked to synaptic plasticity and memory formation(Berry and Nedivi,2017).While comprehensive in vitro studies have been conducted,in vivo studies that directly tackle the mechanism of dendritic transport and translation in regulating spine plasticity spatiotemporally are limited.
