The effects of slope aspects on soil biogeochemical properties and plant communities in forested environments have been studied extensively; however, slope aspect influence on soil microbial communities remains largel...The effects of slope aspects on soil biogeochemical properties and plant communities in forested environments have been studied extensively; however, slope aspect influence on soil microbial communities remains largely unexamined, despite the central role of soil biota in ecosystem functioning. In this study, the communities of both soil bacteria and arbuscular mycorrhizal fungi （AMF） were investigated using tagged pyrosequencing for three types of slope aspects （south-facing aspect, north-facing aspect and flat area） in a boreal forest of the Greater Khingan Mountains, China. The bacterial and AMF community composition differed with slope aspects. Bacterial diversity was the lowest on the north-facing aspect, and AMF diversity was the lowest on the flat area. Aspects also had a significant impact on soil pH and available phosphorus （P） and shrubby biomass. Soil pH and understory shrub biomass were significantly correlated with bacterial communities, and soil available P and shrub biomass showed significant correlations with AMF communities. Our results suggested that slope aspects affected bacterial and AMF communities, mediated by aspect-induced changes in plant community and soil chemical properties （e.g., pH and available P）, which improved the knowledge on the effects of forest slope aspects on aboveground and belowground communities.展开更多
Infrastructure mega-project(IMP) innovation is a complex process characterized by highly diverse innovators, a dynamic life-cycle, and stickiness of innovation knowledge. The IMP's innovation network can be easily...Infrastructure mega-project(IMP) innovation is a complex process characterized by highly diverse innovators, a dynamic life-cycle, and stickiness of innovation knowledge. The IMP's innovation network can be easily broken due to the fact that the network involves many different innovators across different industries and different projects. Further reasons for the fragility of the IMP's innovation network are the dynamics of the IMP life-cycle, the diversity of the IMP's innovative entities, the uniqueness of each IMP, and the temporary nature of each IMP's organizations. The innovation island formed by the breaking of an IMP's innovation network can stifle and harm innovation performance. Drawing from the knowledge-based view as well as innovation network theory, our research identifies the heterogeneous characteristics of IMP innovation. We propose a framework to analyze the formation mechanism of the IMP innovation island from three dimensions—the horizontal innovation island, the vertical innovation island, and the longitudinal innovation island. We look at the Hong Kong-ZhuhaiMacao Bridge project to elaborate the innovation island concept that negatively impacts IMP innovation. We also offer theoretical implications regarding the broader question of how IMPs can manage their innovation in practice.展开更多
The Jiangmen Underground Neutrino Observatory(JUNO)is a large liquid scintillator detector designed to explore many topics in fundamental physics.In this study,the potential of searching for proton decay in the p→νK...The Jiangmen Underground Neutrino Observatory(JUNO)is a large liquid scintillator detector designed to explore many topics in fundamental physics.In this study,the potential of searching for proton decay in the p→νK^(+)mode with JUNO is investigated.The kaon and its decay particles feature a clear three-fold coincidence signature that results in a high efficiency for identification.Moreover,the excellent energy resolution of JUNO permits suppression of the sizable background caused by other delayed signals.Based on these advantages,the detection efficiency for the proton decay via p→νK^(+)is 36.9%±4.9%with a background level of 0.2±0.05(syst)±0.2(stat)events after 10 years of data collection.The estimated sensitivity based on 200 kton-years of exposure is 9.6×1033 years,which is competitive with the current best limits on the proton lifetime in this channel and complements the use of different detection technologies.展开更多
The Jiangmen Underground Neutrino Observatory(JUNO)features a 20 kt multi-purpose underground liquid scintillator sphere as its main detector.Some of JUNO's features make it an excellent location for^8B solar neut...The Jiangmen Underground Neutrino Observatory(JUNO)features a 20 kt multi-purpose underground liquid scintillator sphere as its main detector.Some of JUNO's features make it an excellent location for^8B solar neutrino measurements,such as its low-energy threshold,high energy resolution compared with water Cherenkov detectors,and much larger target mass compared with previous liquid scintillator detectors.In this paper,we present a comprehensive assessment of JUNO's potential for detecting^8B solar neutrinos via the neutrino-electron elastic scattering process.A reduced 2 MeV threshold for the recoil electron energy is found to be achievable,assuming that the intrinsic radioactive background^(238)U and^(232)Th in the liquid scintillator can be controlled to 10^(-17)g/g.With ten years of data acquisition,approximately 60,000 signal and 30,000 background events are expected.This large sample will enable an examination of the distortion of the recoil electron spectrum that is dominated by the neutrino flavor transformation in the dense solar matter,which will shed new light on the inconsistency between the measured electron spectra and the predictions of the standard three-flavor neutrino oscillation framework.IfDelta m^(2)_(21)=4.8times10^(-5);(7.5times10^(-5))eV^(2),JUNO can provide evidence of neutrino oscillation in the Earth at approximately the 3sigma(2sigma)level by measuring the non-zero signal rate variation with respect to the solar zenith angle.Moreover,JUNO can simultaneously measureDelta m^2_(21)using^8B solar neutrinos to a precision of 20% or better,depending on the central value,and to sub-percent precision using reactor antineutrinos.A comparison of these two measurements from the same detector will help understand the current mild inconsistency between the value of Delta m^2_(21)reported by solar neutrino experiments and the KamLAND experiment.展开更多
JUNO is a multi-purpose neutrino observatory under construction in the south of China.This publication presents new sensitivity estimates for the measurement of the △m_(31)^(2),△m_(21)^(2),sin^(2)θ_(12),and sin^(2)...JUNO is a multi-purpose neutrino observatory under construction in the south of China.This publication presents new sensitivity estimates for the measurement of the △m_(31)^(2),△m_(21)^(2),sin^(2)θ_(12),and sin^(2)θ_(13) oscillation parameters using reactor antineutrinos,which is one of the primary physics goals of the experiment.The sensitivities are obtained using the best knowledge available to date on the location and overburden of the experimental site,the nuclear reactors in the surrounding area and beyond,the detector response uncertainties,and the reactor antineutrino spectral shape constraints expected from the TAO satellite detector.It is found that the △m_(21)^(2) and sin^(2)θ_(12) oscillation parameters will be determined to 0.5%precision or better in six years of data collection.In the same period,the △m_(31)^(2) parameter will be determined to about 0.2%precision for each mass ordering hypothesis.The new precision represents approximately an order of magnitude improvement over existing constraints for these three parameters.展开更多
This study used the finite element method （FEM） to analyze the stress field and seepage field of a roller-compacted concrete （RCC） dam, with an upstream impervious layer constructed with different types of concret...This study used the finite element method （FEM） to analyze the stress field and seepage field of a roller-compacted concrete （RCC） dam, with an upstream impervious layer constructed with different types of concrete materials, including three-graded RCC, two-graded RCC, conven- tional vibrated concrete （CVC）, and grout-enriched vibrated RCC （GEVR）, corresponding to the design schemes S 1 through $4. It also evaluated the anti-seepage performance of the imperious layer in the four design schemes under the normal water level and flood-check level. Stress field analysis of a retaining section and discharge section shows that the maximum tensile stress occurs near the dam heel, the maximum compressive stress occurs near the dam toe, and the stress distributions in the four schemes can satisfy the stress control criteria. Seepage field analysis shows that the uplift pressure heads in schemes S3 and S4 descend rapidly in the anti-seepage region, and that the calculated results of daily seepage flow under the steady seepage condition in these two schemes are about 30%-50% lower than those in the other two schemes, demonstrating that CVC and GEVR show better anti-seepage performance. The results provide essential parameters such as the uplift pressure head and seelga^e flow for physical model tests and anti-seepage structure selection in RCC dams.展开更多
Background:The mechanisms underlying lesions of dopaminergic(DA)neurons,an essential pathology of Parkinson’s disease(PD),are largely unknown,although oxidative stress is recognized as a key factor.We have previously...Background:The mechanisms underlying lesions of dopaminergic(DA)neurons,an essential pathology of Parkinson’s disease(PD),are largely unknown,although oxidative stress is recognized as a key factor.We have previously shown that the pro-oxidative aldehyde acrolein is a critical factor in PD pathology,and that acrolein scavenger hydralazine can reduce the elevated acrolein,mitigate DA neuron death,and alleviate motor deficits in a 6-hydroxydopamine(6-OHDA)rat model.As such,we hypothesize that a structurally distinct acrolein scavenger,dimercaprol(DP),can also offer neuroprotection and behavioral benefits.Methods:DP was used to lower the elevated levels of acrolein in the basal ganglia of 6-OHDA rats.The acrolein levels and related pathologies were measured by immunohistochemistry.Locomotor and behavioral effects of 6-OHDA injections and DP treatment were examined using the open field test and rotarod test.Pain was assessed using mechanical allodynia,cold hypersensitivity,and plantar tests.Finally,the effects of DP were assessed in vitro on SK-N-SH dopaminergic cells exposed to acrolein.Results:DP reduced acrolein and reversed the upregulation of pain-sensing transient receptor potential ankyrin 1(TRPA1)channels in the substantia nigra,striatum,and cortex.DP also mitigated both motor and sensory deficits typical of PD.In addition,DP lowered acrolein and protected DA-like cells in vitro.Acrolein’s ability to upregulate TRPA1 was also verified in vitro using cell lines.Conclusions:These results further elucidated the acrolein-mediated pathogenesis and reinforced the critical role of acrolein in PD while providing strong arguments for anti-acrolein treatments as a novel and feasible strategy to combat neurodegeneration in PD.Considering the extensive involvement of acrolein in various nervous system illnesses and beyond,anti-acrolein strategies may have wide applications and broad impacts on human health.展开更多
1 Introduction Megaprojects are a critical aspect of socio-economic development that can have huge effects on local communities,the environment,society,politics,or locals9 way of life(Zeng et al.,2015;Denicol et al.,2...1 Introduction Megaprojects are a critical aspect of socio-economic development that can have huge effects on local communities,the environment,society,politics,or locals9 way of life(Zeng et al.,2015;Denicol et al.,2020).Megaproject social responsibility(MSR)refers to “the policies and practices of stakeholders through the whole project lifecycle that reflect responsibilities for the well-being of the wide society”(Zeng et al.,2015).MSR governance refers to socially responsible actions of relevant stakeholders to alleviate and eliminate a megaprojecfs negative effects on socio-economic and environmental outcomes during the megaprojecfs entire lifecycle(Lin et al.,2017;Ma et al.,2017).展开更多
Traumatic brain injury is among the most common causes of death and disability in youth and young adults.In addition to the acute risk of morbidity with moderate to severe injuries,traumatic brain injury is associated...Traumatic brain injury is among the most common causes of death and disability in youth and young adults.In addition to the acute risk of morbidity with moderate to severe injuries,traumatic brain injury is associated with a number of chronic neurological and neuropsychiatric sequelae including neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease.However,despite the high incidence of traumatic brain injuries and the established clinical correlation with neurodegeneration,the causative factors linking these processes have not yet been fully elucidated.Apart from removal from activity,few,if any prophylactic treatments against post-traumatic brain injury neurodegeneration exist.Therefore,it is imperative to understand the pathophysiological mechanisms of traumatic brain injury and neurodegeneration in order to identify potential factors that initiate neurodegenerative processes.Oxidative stress,neuroinflammation,and glutamatergic excitotoxicity have previously been implicated in both secondary brain injury and neurodegeneration.In particular,reactive oxygen species appear to be key in mediating molecular insult in neuroinflammation and excitotoxicity.As such,it is likely that post injury oxidative stress is a key mechanism which links traumatic brain injury to increased risk of neurodegeneration.Consequently,reactive oxygen species and their subsequent byproducts may serve as novel fluid markers for identification and monitoring of cellular damage.Furthermore,these reactive species may further serve as a suitable therapeutic target to reduce the risk of post-injury neurodegeneration and provide long term quality of life improvements for those suffering from traumatic brain injury.展开更多
Background:Wound healing processes are influenced by macronutrient intake(protein,carbohydrate and fat).The most favourable diet for cutaneous wound healing is not known,although highprotein diets are currently favour...Background:Wound healing processes are influenced by macronutrient intake(protein,carbohydrate and fat).The most favourable diet for cutaneous wound healing is not known,although highprotein diets are currently favoured clinically.This experimental study investigates the optimal macronutrient balance for cutaneous wound healing using a mouse model and the Geometric Framework,a nutrient modelling method,capable of analyzing the individual and interactive effects of a wide spectrum of macronutrient intake.Methods:Two adjacent and identical full-thickness skin excisions(1 cm^(2))were surgically created on the dorsal area of male C57BL/6 mice.Mice were then allocated to one of 12 high-energy diets that varied in protein,carbohydrate and fat content.In select diets,wound healing processes,cytokine expression,energy expenditure,body composition,muscle and fat reserves were assessed.Results:Using the Geometric Framework,we show that a low-protein intake,coupled with a balanced intake of carbohydrate and fat is optimal for wound healing.Mice fed a low-protein diet progressed quickly through wound healing stages with favourable wound inflammatory cytokine expression and significantly accelerated collagen production.These local processes were associated with an increased early systemic inflammatory response and a higher overall energy expenditure,related to metabolic changes occurring in key macronutrient reserves in lean body mass and fat depots.Conclusions:The results suggest that a low-protein diet may have a greater potential to accelerate wound healing than the current clinically used high-protein diets.展开更多
OBJECTIVE Dopamine receptors(DRs) are involved in the development and treatment of many neuropsychiatric disorders.Currently available dopaminergic drugs modulate both DRD2 and DRD3,leading to side effects and uncerta...OBJECTIVE Dopamine receptors(DRs) are involved in the development and treatment of many neuropsychiatric disorders.Currently available dopaminergic drugs modulate both DRD2 and DRD3,leading to side effects and uncertainty as to the roles each DR subtype plays physiologically.Our lab employed high throughput screening paradigms to discover highly selective modulators for the DRD3.METHODS The NIH Molecular Libraries Program 400,000 + small molecule library was screened using the Discove Rx Path Hunter?β-arrestin assay for compounds that activate the DRD3 without effects on the DRD2.Confirmation and counter-screens assessed selectivity and mechanisms of action.We identified 62 potential agonists,and chose the most promising to perform a structure-activity relationship(SAR) study to increase potency while maintaining selectivity.The lead compound identified through this process,ML417,was also characterized using bioluminescence resonance energy transfer(BRET)-based β-arrestin recruitment and G-protein activation assays as well as p-ERK assays.Potential neuroprotective properties of this compound were assessed using a SHSY5 Y neuronal cell model.RESULTS ML417 displays potent,DRD3-selective agonist activity in multiple functional assays.Binding and functional GPCR screens(>165 receptors) show ML417 has limited cross-reactivity with other GPCRs.ML417 also displays superior(compared to the reference compound pramipexole),dose-dependent protection against a decrease in neurite length induced by 10 μmol·L^(-1) of the neurotoxin,6-hydroxydopamine,in the SHSY5 Y cell model.CONCLUSION We have discovered and characterized ML417,a potent and highly selective DRD3 agonist.This compound will be useful as a research tool,and may prove useful as a therapeutic drug lead.展开更多
A great deal of scientific research in the world aims at discovering the facts about the world so that we understand it better and find solutions to problems. Data enabling technology plays an important role in modern...A great deal of scientific research in the world aims at discovering the facts about the world so that we understand it better and find solutions to problems. Data enabling technology plays an important role in modern scientific discovery and technologic advancement. The importance of good information was long recognized by prominent leaders such as Sun Tzu and Napoleon. Factual data enables managers to measure, to understand their businesses, and to directly translate that knowledge into improved decision making and performance. This position paper argues that data analytics is ready to change engineering management in the following areas: 1) by making relevant historical data available to the manager at the time when it's needed; 2) by filtering out actionable intelligence from the ocean of data; and 3) by integrating useful data from multiple sources to support quantitative decision-making. Considering the unique need for engineering management, the paper proposes researchable topics in the two broad areas of data acquisition and data analytics. The purpose of the paper is to provoke discussion from peers and to encourage research activity.展开更多
Background:It is increasingly clear that in addition to myelin disruption,axonal degeneration may also represent a key pathology in multiple sclerosis(MS).Hence,elucidating the mechanisms of axonal degeneration may no...Background:It is increasingly clear that in addition to myelin disruption,axonal degeneration may also represent a key pathology in multiple sclerosis(MS).Hence,elucidating the mechanisms of axonal degeneration may not only enhance our understanding of the overall MS pathology,but also elucidate additional therapeutic targets.The objective of this study is assess the degree of axonal membrane disruption and its significance in motor deficits in EAE mice.Methods:Experimental Autoimmune Encephalomyelitis was induced in mice by subcutaneous injection of myelin oligodendrocyte glycoprotein/complete Freud’s adjuvant emulsion,followed by two intraperitoneal injections of pertussis toxin.Behavioral assessment was performed using a 5-point scale.Horseradish Peroxidase Exclusion test was used to quantify the disruption of axonal membrane.Polyethylene glycol was prepared as a 30%(w/v)solution in phosphate buffered saline and injected intraperitoneally.Results:We have found evidence of axonal membrane disruption in EAE mice when symptoms peak and to a lesser degree,in the pre-symptomatic stage of EAE mice.Furthermore,polyethylene glycol(PEG),a known membrane fusogen,significantly reduces axonal membrane disruption in EAE mice.Such PEG-mediated membrane repair was accompanied by significant amelioration of behavioral deficits,including a delay in the emergence of motor deficits,a delay of the emergence of peak symptom,and a reduction in the severity of peak symptom.Conclusions:The current study is the first indication that axonal membrane disruption may be an important part of the pathology in EAE mice and may underlies behavioral deficits.Our study also presents the initial observation that PEG may be a therapeutic agent that can repair axolemma,arrest axonal degeneration and reduce motor deficits in EAE mice.展开更多
基金We thank Ms. LIU Weili, Dr. CAI Wenhua, Mr. LIU Bo, and Dr. FANG Lei from the Institute of Ap- plied Ecology, Chinese Academy of Sciences for assis- tance in sampling and Dr. XIONG Jingbo from the Ningbo University of China for assistance in bioinfor- matic analysis. This research was supported by the Strategic Priority Research Program of Chinese Aca- demy of Sciences （No. XDB15010101）, the National Basic Research Program （973 Program） of China （No. 2014CB954002）, and the National Natural Science Foundation of China （No. 41371254）.
文摘The effects of slope aspects on soil biogeochemical properties and plant communities in forested environments have been studied extensively; however, slope aspect influence on soil microbial communities remains largely unexamined, despite the central role of soil biota in ecosystem functioning. In this study, the communities of both soil bacteria and arbuscular mycorrhizal fungi （AMF） were investigated using tagged pyrosequencing for three types of slope aspects （south-facing aspect, north-facing aspect and flat area） in a boreal forest of the Greater Khingan Mountains, China. The bacterial and AMF community composition differed with slope aspects. Bacterial diversity was the lowest on the north-facing aspect, and AMF diversity was the lowest on the flat area. Aspects also had a significant impact on soil pH and available phosphorus （P） and shrubby biomass. Soil pH and understory shrub biomass were significantly correlated with bacterial communities, and soil available P and shrub biomass showed significant correlations with AMF communities. Our results suggested that slope aspects affected bacterial and AMF communities, mediated by aspect-induced changes in plant community and soil chemical properties （e.g., pH and available P）, which improved the knowledge on the effects of forest slope aspects on aboveground and belowground communities.
基金funded by the National Natural Science Foundation of China(Grant Nos.71390525 and 71620107004)the Shanghai Excellent Academic Leaders Program(Grant No.14XD1402200)
文摘Infrastructure mega-project(IMP) innovation is a complex process characterized by highly diverse innovators, a dynamic life-cycle, and stickiness of innovation knowledge. The IMP's innovation network can be easily broken due to the fact that the network involves many different innovators across different industries and different projects. Further reasons for the fragility of the IMP's innovation network are the dynamics of the IMP life-cycle, the diversity of the IMP's innovative entities, the uniqueness of each IMP, and the temporary nature of each IMP's organizations. The innovation island formed by the breaking of an IMP's innovation network can stifle and harm innovation performance. Drawing from the knowledge-based view as well as innovation network theory, our research identifies the heterogeneous characteristics of IMP innovation. We propose a framework to analyze the formation mechanism of the IMP innovation island from three dimensions—the horizontal innovation island, the vertical innovation island, and the longitudinal innovation island. We look at the Hong Kong-ZhuhaiMacao Bridge project to elaborate the innovation island concept that negatively impacts IMP innovation. We also offer theoretical implications regarding the broader question of how IMPs can manage their innovation in practice.
基金supported by the Chinese Academy of Sciencesthe National Key R&D Program of China+22 种基金the CAS Center for Excellence in Particle PhysicsWuyi Universitythe Tsung-Dao Lee Institute of Shanghai Jiao Tong University in Chinathe Institut National de Physique Nucléaire et de Physique de Particules (IN2P3) in Francethe Istituto Nazionale di Fisica Nucleare (INFN) in Italythe Italian-Chinese collaborative research program MAECI-NSFCthe Fond de la Recherche Scientifique (F.R.S-FNRS)FWO under the "Excellence of Science-EOS" in Belgiumthe Conselho Nacional de Desenvolvimento Científico e Tecnològico in Brazilthe Agencia Nacional de Investigacion y Desarrollo in Chilethe Charles University Research Centrethe Ministry of Education,Youth,and Sports in Czech Republicthe Deutsche Forschungsgemeinschaft (DFG)the Helmholtz Associationthe Cluster of Excellence PRISMA+ in Germanythe Joint Institute of Nuclear Research (JINR)Lomonosov Moscow State University in Russiathe joint Russian Science Foundation (RSF)National Natural Science Foundation of China (NSFC) research programthe MOST and MOE in Taiwan,Chinathe Chulalongkorn UniversitySuranaree University of Technology in Thailandthe University of California at Irvine in USA
文摘The Jiangmen Underground Neutrino Observatory(JUNO)is a large liquid scintillator detector designed to explore many topics in fundamental physics.In this study,the potential of searching for proton decay in the p→νK^(+)mode with JUNO is investigated.The kaon and its decay particles feature a clear three-fold coincidence signature that results in a high efficiency for identification.Moreover,the excellent energy resolution of JUNO permits suppression of the sizable background caused by other delayed signals.Based on these advantages,the detection efficiency for the proton decay via p→νK^(+)is 36.9%±4.9%with a background level of 0.2±0.05(syst)±0.2(stat)events after 10 years of data collection.The estimated sensitivity based on 200 kton-years of exposure is 9.6×1033 years,which is competitive with the current best limits on the proton lifetime in this channel and complements the use of different detection technologies.
基金This work was supported by the Chinese Academy of Sciences,the National Key R&D Program of China,the CAS Center for Excellence in Particle Physics,the Joint Large Scale Scientific Facility Funds of the NSFC and CAS,Wuyi University,and the Tsung-Dao Lee Instiute of Shanghai Jiao Tong University in China,the In stiut National de Physique Nucleaire et de Physique de Particules(IN2P3)in France,the Istituto Nazionale di Fisica Nucleare(INFN)in Italy,the Fond de la Recherche Scintifique(F.R.S-FNRS)and FWO under the"Excellence of Science-EOS"in Belgium,the Conselho Nacional de Desenvolvimento Cientificoce Tecnologico in Brazil,the Agencia Nacional de Investigacion y Desrrollo in Chile,the Charles University Research Centre and the Ministry of Education,Youth,and Sports in Czech Republic,the Deutsche Forschungsgemeinschaft(DFG),the Helmholtz Association,and the Cluster of Exellence PRISMA+in Germany,the Joint Institute of Nuclear Research(JINR),Lomonosov Moscow State University,and Russian Foundation for Basic Research(RFBR)in Russia,the MOST and MOE in Taiwan,the Chu-lalongkorm University and Suranaree University of Technology in Thailand,and the University of aliformia at Irvine in USA.
文摘The Jiangmen Underground Neutrino Observatory(JUNO)features a 20 kt multi-purpose underground liquid scintillator sphere as its main detector.Some of JUNO's features make it an excellent location for^8B solar neutrino measurements,such as its low-energy threshold,high energy resolution compared with water Cherenkov detectors,and much larger target mass compared with previous liquid scintillator detectors.In this paper,we present a comprehensive assessment of JUNO's potential for detecting^8B solar neutrinos via the neutrino-electron elastic scattering process.A reduced 2 MeV threshold for the recoil electron energy is found to be achievable,assuming that the intrinsic radioactive background^(238)U and^(232)Th in the liquid scintillator can be controlled to 10^(-17)g/g.With ten years of data acquisition,approximately 60,000 signal and 30,000 background events are expected.This large sample will enable an examination of the distortion of the recoil electron spectrum that is dominated by the neutrino flavor transformation in the dense solar matter,which will shed new light on the inconsistency between the measured electron spectra and the predictions of the standard three-flavor neutrino oscillation framework.IfDelta m^(2)_(21)=4.8times10^(-5);(7.5times10^(-5))eV^(2),JUNO can provide evidence of neutrino oscillation in the Earth at approximately the 3sigma(2sigma)level by measuring the non-zero signal rate variation with respect to the solar zenith angle.Moreover,JUNO can simultaneously measureDelta m^2_(21)using^8B solar neutrinos to a precision of 20% or better,depending on the central value,and to sub-percent precision using reactor antineutrinos.A comparison of these two measurements from the same detector will help understand the current mild inconsistency between the value of Delta m^2_(21)reported by solar neutrino experiments and the KamLAND experiment.
基金Supported by the Chinese Academy of Sciencesthe National Key R&D Program of China+18 种基金the CAS Center for Excellence in Particle Physics,Wuyi Universitythe Tsung-Dao Lee Institute of Shanghai Jiao Tong University in Chinathe Institut National de Physique Nucléaire et de Physique de Particules(IN2P3)in Francethe Istituto Nazionale di Fisica Nucleare(INFN)in Italythe Italian-Chinese collaborative research program MAECI-NSFCthe Fond de la Recherche Scientifique(F.R.S-FNRS)FWO under the“Excellence of Science-EOS in Belgium”the Conselho Nacional de Desenvolvimento Científico e Tecnològico in Brazilthe Agencia Nacional de Investigacion y Desarrollo and ANID-Millennium Science Initiative Program-ICN2019_044 in Chilethe Charles University Research Centre and the Ministry of Education,Youth,and Sports in Czech Republicthe Deutsche Forschungsgemeinschaft(DFG)the Helmholtz Associationthe Cluster of Excellence PRISMA+in Germanythe Joint Institute of Nuclear Research(JINR)and Lomonosov Moscow State University in Russiathe joint Russian Science Foundation(RSF)National Natural Science Foundation of China(NSFC)research programthe MOST and MOE in Taiwanthe Chulalongkorn University and Suranaree University of Technology in Thailand,University of California at Irvinethe National Science Foundation in USA。
文摘JUNO is a multi-purpose neutrino observatory under construction in the south of China.This publication presents new sensitivity estimates for the measurement of the △m_(31)^(2),△m_(21)^(2),sin^(2)θ_(12),and sin^(2)θ_(13) oscillation parameters using reactor antineutrinos,which is one of the primary physics goals of the experiment.The sensitivities are obtained using the best knowledge available to date on the location and overburden of the experimental site,the nuclear reactors in the surrounding area and beyond,the detector response uncertainties,and the reactor antineutrino spectral shape constraints expected from the TAO satellite detector.It is found that the △m_(21)^(2) and sin^(2)θ_(12) oscillation parameters will be determined to 0.5%precision or better in six years of data collection.In the same period,the △m_(31)^(2) parameter will be determined to about 0.2%precision for each mass ordering hypothesis.The new precision represents approximately an order of magnitude improvement over existing constraints for these three parameters.
基金supported by the National Basic Research Program of China(Grant No.2013CB035903)the National Natural Science Foundation of China(Grants No.51321065 and 51209159)
文摘This study used the finite element method （FEM） to analyze the stress field and seepage field of a roller-compacted concrete （RCC） dam, with an upstream impervious layer constructed with different types of concrete materials, including three-graded RCC, two-graded RCC, conven- tional vibrated concrete （CVC）, and grout-enriched vibrated RCC （GEVR）, corresponding to the design schemes S 1 through $4. It also evaluated the anti-seepage performance of the imperious layer in the four design schemes under the normal water level and flood-check level. Stress field analysis of a retaining section and discharge section shows that the maximum tensile stress occurs near the dam heel, the maximum compressive stress occurs near the dam toe, and the stress distributions in the four schemes can satisfy the stress control criteria. Seepage field analysis shows that the uplift pressure heads in schemes S3 and S4 descend rapidly in the anti-seepage region, and that the calculated results of daily seepage flow under the steady seepage condition in these two schemes are about 30%-50% lower than those in the other two schemes, demonstrating that CVC and GEVR show better anti-seepage performance. The results provide essential parameters such as the uplift pressure head and seelga^e flow for physical model tests and anti-seepage structure selection in RCC dams.
基金This work was supported by the National Institutes of Health(Grant#NS090244 and NS115094 to RS)as well as grants from the National Key Technology Support Program(2014BAI03B01 to Z.C)Sichuan International Science and Technology Innovation Cooperation Project(2020YFH0148 to Z.C).
文摘Background:The mechanisms underlying lesions of dopaminergic(DA)neurons,an essential pathology of Parkinson’s disease(PD),are largely unknown,although oxidative stress is recognized as a key factor.We have previously shown that the pro-oxidative aldehyde acrolein is a critical factor in PD pathology,and that acrolein scavenger hydralazine can reduce the elevated acrolein,mitigate DA neuron death,and alleviate motor deficits in a 6-hydroxydopamine(6-OHDA)rat model.As such,we hypothesize that a structurally distinct acrolein scavenger,dimercaprol(DP),can also offer neuroprotection and behavioral benefits.Methods:DP was used to lower the elevated levels of acrolein in the basal ganglia of 6-OHDA rats.The acrolein levels and related pathologies were measured by immunohistochemistry.Locomotor and behavioral effects of 6-OHDA injections and DP treatment were examined using the open field test and rotarod test.Pain was assessed using mechanical allodynia,cold hypersensitivity,and plantar tests.Finally,the effects of DP were assessed in vitro on SK-N-SH dopaminergic cells exposed to acrolein.Results:DP reduced acrolein and reversed the upregulation of pain-sensing transient receptor potential ankyrin 1(TRPA1)channels in the substantia nigra,striatum,and cortex.DP also mitigated both motor and sensory deficits typical of PD.In addition,DP lowered acrolein and protected DA-like cells in vitro.Acrolein’s ability to upregulate TRPA1 was also verified in vitro using cell lines.Conclusions:These results further elucidated the acrolein-mediated pathogenesis and reinforced the critical role of acrolein in PD while providing strong arguments for anti-acrolein treatments as a novel and feasible strategy to combat neurodegeneration in PD.Considering the extensive involvement of acrolein in various nervous system illnesses and beyond,anti-acrolein strategies may have wide applications and broad impacts on human health.
基金This research is supported in part by the National Natural Science Foundation of China(Grant Nos.71942006 and 71620107004)Humanities and Social Sciences Research Project of the Ministry of Education of China(Grant No.20YJC630099).
文摘1 Introduction Megaprojects are a critical aspect of socio-economic development that can have huge effects on local communities,the environment,society,politics,or locals9 way of life(Zeng et al.,2015;Denicol et al.,2020).Megaproject social responsibility(MSR)refers to “the policies and practices of stakeholders through the whole project lifecycle that reflect responsibilities for the well-being of the wide society”(Zeng et al.,2015).MSR governance refers to socially responsible actions of relevant stakeholders to alleviate and eliminate a megaprojecfs negative effects on socio-economic and environmental outcomes during the megaprojecfs entire lifecycle(Lin et al.,2017;Ma et al.,2017).
文摘Traumatic brain injury is among the most common causes of death and disability in youth and young adults.In addition to the acute risk of morbidity with moderate to severe injuries,traumatic brain injury is associated with a number of chronic neurological and neuropsychiatric sequelae including neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease.However,despite the high incidence of traumatic brain injuries and the established clinical correlation with neurodegeneration,the causative factors linking these processes have not yet been fully elucidated.Apart from removal from activity,few,if any prophylactic treatments against post-traumatic brain injury neurodegeneration exist.Therefore,it is imperative to understand the pathophysiological mechanisms of traumatic brain injury and neurodegeneration in order to identify potential factors that initiate neurodegenerative processes.Oxidative stress,neuroinflammation,and glutamatergic excitotoxicity have previously been implicated in both secondary brain injury and neurodegeneration.In particular,reactive oxygen species appear to be key in mediating molecular insult in neuroinflammation and excitotoxicity.As such,it is likely that post injury oxidative stress is a key mechanism which links traumatic brain injury to increased risk of neurodegeneration.Consequently,reactive oxygen species and their subsequent byproducts may serve as novel fluid markers for identification and monitoring of cellular damage.Furthermore,these reactive species may further serve as a suitable therapeutic target to reduce the risk of post-injury neurodegeneration and provide long term quality of life improvements for those suffering from traumatic brain injury.
基金supported by the ANZAC Research Institute Seed Fund.
文摘Background:Wound healing processes are influenced by macronutrient intake(protein,carbohydrate and fat).The most favourable diet for cutaneous wound healing is not known,although highprotein diets are currently favoured clinically.This experimental study investigates the optimal macronutrient balance for cutaneous wound healing using a mouse model and the Geometric Framework,a nutrient modelling method,capable of analyzing the individual and interactive effects of a wide spectrum of macronutrient intake.Methods:Two adjacent and identical full-thickness skin excisions(1 cm^(2))were surgically created on the dorsal area of male C57BL/6 mice.Mice were then allocated to one of 12 high-energy diets that varied in protein,carbohydrate and fat content.In select diets,wound healing processes,cytokine expression,energy expenditure,body composition,muscle and fat reserves were assessed.Results:Using the Geometric Framework,we show that a low-protein intake,coupled with a balanced intake of carbohydrate and fat is optimal for wound healing.Mice fed a low-protein diet progressed quickly through wound healing stages with favourable wound inflammatory cytokine expression and significantly accelerated collagen production.These local processes were associated with an increased early systemic inflammatory response and a higher overall energy expenditure,related to metabolic changes occurring in key macronutrient reserves in lean body mass and fat depots.Conclusions:The results suggest that a low-protein diet may have a greater potential to accelerate wound healing than the current clinically used high-protein diets.
基金supported by National Institute of Neurological Disorders and Stroke Intramural Research Program
文摘OBJECTIVE Dopamine receptors(DRs) are involved in the development and treatment of many neuropsychiatric disorders.Currently available dopaminergic drugs modulate both DRD2 and DRD3,leading to side effects and uncertainty as to the roles each DR subtype plays physiologically.Our lab employed high throughput screening paradigms to discover highly selective modulators for the DRD3.METHODS The NIH Molecular Libraries Program 400,000 + small molecule library was screened using the Discove Rx Path Hunter?β-arrestin assay for compounds that activate the DRD3 without effects on the DRD2.Confirmation and counter-screens assessed selectivity and mechanisms of action.We identified 62 potential agonists,and chose the most promising to perform a structure-activity relationship(SAR) study to increase potency while maintaining selectivity.The lead compound identified through this process,ML417,was also characterized using bioluminescence resonance energy transfer(BRET)-based β-arrestin recruitment and G-protein activation assays as well as p-ERK assays.Potential neuroprotective properties of this compound were assessed using a SHSY5 Y neuronal cell model.RESULTS ML417 displays potent,DRD3-selective agonist activity in multiple functional assays.Binding and functional GPCR screens(>165 receptors) show ML417 has limited cross-reactivity with other GPCRs.ML417 also displays superior(compared to the reference compound pramipexole),dose-dependent protection against a decrease in neurite length induced by 10 μmol·L^(-1) of the neurotoxin,6-hydroxydopamine,in the SHSY5 Y cell model.CONCLUSION We have discovered and characterized ML417,a potent and highly selective DRD3 agonist.This compound will be useful as a research tool,and may prove useful as a therapeutic drug lead.
文摘A great deal of scientific research in the world aims at discovering the facts about the world so that we understand it better and find solutions to problems. Data enabling technology plays an important role in modern scientific discovery and technologic advancement. The importance of good information was long recognized by prominent leaders such as Sun Tzu and Napoleon. Factual data enables managers to measure, to understand their businesses, and to directly translate that knowledge into improved decision making and performance. This position paper argues that data analytics is ready to change engineering management in the following areas: 1) by making relevant historical data available to the manager at the time when it's needed; 2) by filtering out actionable intelligence from the ocean of data; and 3) by integrating useful data from multiple sources to support quantitative decision-making. Considering the unique need for engineering management, the paper proposes researchable topics in the two broad areas of data acquisition and data analytics. The purpose of the paper is to provoke discussion from peers and to encourage research activity.
基金This work was supported by the State of Indiana and the Indiana Clinical and Translational Sciences Institute(PHS NCCR#TL1RR025759 and#RR025761).
文摘Background:It is increasingly clear that in addition to myelin disruption,axonal degeneration may also represent a key pathology in multiple sclerosis(MS).Hence,elucidating the mechanisms of axonal degeneration may not only enhance our understanding of the overall MS pathology,but also elucidate additional therapeutic targets.The objective of this study is assess the degree of axonal membrane disruption and its significance in motor deficits in EAE mice.Methods:Experimental Autoimmune Encephalomyelitis was induced in mice by subcutaneous injection of myelin oligodendrocyte glycoprotein/complete Freud’s adjuvant emulsion,followed by two intraperitoneal injections of pertussis toxin.Behavioral assessment was performed using a 5-point scale.Horseradish Peroxidase Exclusion test was used to quantify the disruption of axonal membrane.Polyethylene glycol was prepared as a 30%(w/v)solution in phosphate buffered saline and injected intraperitoneally.Results:We have found evidence of axonal membrane disruption in EAE mice when symptoms peak and to a lesser degree,in the pre-symptomatic stage of EAE mice.Furthermore,polyethylene glycol(PEG),a known membrane fusogen,significantly reduces axonal membrane disruption in EAE mice.Such PEG-mediated membrane repair was accompanied by significant amelioration of behavioral deficits,including a delay in the emergence of motor deficits,a delay of the emergence of peak symptom,and a reduction in the severity of peak symptom.Conclusions:The current study is the first indication that axonal membrane disruption may be an important part of the pathology in EAE mice and may underlies behavioral deficits.Our study also presents the initial observation that PEG may be a therapeutic agent that can repair axolemma,arrest axonal degeneration and reduce motor deficits in EAE mice.
