In this study,we present a novel nodal integration-based particle finite element method(N-PFEM)designed for the dynamic analysis of saturated soils.Our approach incorporates the nodal integration technique into a gene...In this study,we present a novel nodal integration-based particle finite element method(N-PFEM)designed for the dynamic analysis of saturated soils.Our approach incorporates the nodal integration technique into a generalised Hellinger-Reissner(HR)variational principle,creating an implicit PFEM formulation.To mitigate the volumetric locking issue in low-order elements,we employ a node-based strain smoothing technique.By discretising field variables at the centre of smoothing cells,we achieve nodal integration over cells,eliminating the need for sophisticated mapping operations after re-meshing in the PFEM.We express the discretised governing equations as a min-max optimisation problem,which is further reformulated as a standard second-order cone programming(SOCP)problem.Stresses,pore water pressure,and displacements are simultaneously determined using the advanced primal-dual interior point method.Consequently,our numerical model offers improved accuracy for stresses and pore water pressure compared to the displacement-based PFEM formulation.Numerical experiments demonstrate that the N-PFEM efficiently captures both transient and long-term hydro-mechanical behaviour of saturated soils with high accuracy,obviating the need for stabilisation or regularisation techniques commonly employed in other nodal integration-based PFEM approaches.This work holds significant implications for the development of robust and accurate numerical tools for studying saturated soil dynamics.展开更多
BACKGROUND Among the most frequent hip fractures are trochanteric fractures,which usually occur from low-energy trauma like minor falls,especially in older people with osteoporotic bones.AIM To evaluate the treatment ...BACKGROUND Among the most frequent hip fractures are trochanteric fractures,which usually occur from low-energy trauma like minor falls,especially in older people with osteoporotic bones.AIM To evaluate the treatment efficacy of dynamic condylar screws(DCS)and proximal femoral nails(PFN)for unstable intertrochanteric fractures.METHODS To find pertinent randomized controlled trials and retrospective observational studies comparing PFN with DCS for the management of unstable femoral intertrochanteric fractures,a thorough search was carried out.For research studies published between January 1996 and April 2024,PubMed,EMBASE,Scopus,Web of Science,Cochrane Library,and Google Scholar were all searched.The complete texts of the papers were retrieved,vetted,and independently examined by two investigators.Disputes were settled by consensus,and any disagreements that persisted were arbitrated by a third author.RESULTS This study included six articles,comprising a total of 173 patients.Compared to the DCS,the PFN had a shorter operation time[mean difference(MD):-41.7 min,95%confidence interval(95%CI):-63.04 to-20.35,P=0.0001],higher success rates with closed reduction techniques[risk ratio(RR):34.05,95%CI:11.12-104.31,P<0.00001],and required less intraoperative blood transfusion(MD:-1.4 units,95%CI:-1.80 to-1.00,P<0.00001).Additionally,the PFN showed shorter fracture union time(MD:-6.92 wk,95%CI:-10.27 to-3.57,P<0.0001)and a lower incidence of reoperation(RR:0.37,95%CI:0.17-0.82,P=0.01).However,there was no discernible variation regarding hospital stay,implant-related complications,and infections.CONCLUSION Compared to DCS,PFN offers shorter operative times,reduces the blood transfusions requirements,achieves higher closed reduction success,enables faster fracture healing,and lowers reoperation incidence.展开更多
Traumatic brain injury(TBI)is a public health problem with an undue economic burden that impacts nearly every age,ethnic,and gender group across the globe(Capizzi et al.,2020).TBIs are often sustained during a dynamic...Traumatic brain injury(TBI)is a public health problem with an undue economic burden that impacts nearly every age,ethnic,and gender group across the globe(Capizzi et al.,2020).TBIs are often sustained during a dynamic range of exposures to energetic environmental forces and as such outcomes are typically heterogeneous regarding severity and pathology(Capizzi et al.,2020).展开更多
γ-Secretase,called“the proteasome of the membrane,”is a membrane-embedded protease complex that cleaves 150+peptide substrates with central roles in biology and medicine,including amyloid precursor protein and the ...γ-Secretase,called“the proteasome of the membrane,”is a membrane-embedded protease complex that cleaves 150+peptide substrates with central roles in biology and medicine,including amyloid precursor protein and the Notch family of cell-surface receptors.Mutations inγ-secretase and amyloid precursor protein lead to early-onset familial Alzheimer’s disease.γ-Secretase has thus served as a critical drug target for treating familial Alzheimer’s disease and the more common late-onset Alzheimer’s disease as well.However,critical gaps remain in understanding the mechanisms of processive proteolysis of substrates,the effects of familial Alzheimer’s disease mutations,and allosteric modulation of substrate cleavage byγ-secretase.In this review,we focus on recent studies of structural dynamic mechanisms ofγ-secretase.Different mechanisms,including the“Fit-Stay-Trim,”“Sliding-Unwinding,”and“Tilting-Unwinding,”have been proposed for substrate proteolysis of amyloid precursor protein byγ-secretase based on all-atom molecular dynamics simulations.While an incorrect registry of the Notch1 substrate was identified in the cryo-electron microscopy structure of Notch1-boundγ-secretase,molecular dynamics simulations on a resolved model of Notch1-boundγ-secretase that was reconstructed using the amyloid precursor protein-boundγ-secretase as a template successfully capturedγ-secretase activation for proper cleavages of both wildtype and mutant Notch,being consistent with biochemical experimental findings.The approach could be potentially applied to decipher the processing mechanisms of various substrates byγ-secretase.In addition,controversy over the effects of familial Alzheimer’s disease mutations,particularly the issue of whether they stabilize or destabilizeγ-secretase-substrate complexes,is discussed.Finally,an outlook is provided for future studies ofγ-secretase,including pathways of substrate binding and product release,effects of modulators on familial Alzheimer’s disease mutations of theγ-secretase-substrate complexes.Comprehensive understanding of the functional mechanisms ofγ-secretase will greatly facilitate the rational design of effective drug molecules for treating familial Alzheimer’s disease and perhaps Alzheimer’s disease in general.展开更多
The microstructure simulation during the multi-pass hot rolling of AM50 alloy was studied by DEFORM-3D. The excellent agreement with the experiment observations shows that the present modeling and user routine are fea...The microstructure simulation during the multi-pass hot rolling of AM50 alloy was studied by DEFORM-3D. The excellent agreement with the experiment observations shows that the present modeling and user routine are feasible for the reproduce of the hot rolling process. The multi-pass hot rolling contributes to the achievement of a uniformly recrystallized microstructure with fine grains in the rolled sheet. The sheet temperature before the finish rolling strongly affects the final grain size, but hardly affects the grain size distribution. This modeling and the user routine also have a potential to be applied in the researches of the other multi-pass hot deformation process.展开更多
准确计算户内变电站大型、复杂的噪声场分布,进而评价可采用降噪措施的减噪效果,是解决户内变电站噪声污染的关键问题。为此,综合声学有限元法(finite element method,FEM)求解复杂声场收敛性好及精度高的优点,及声学边界元法(boundary ...准确计算户内变电站大型、复杂的噪声场分布,进而评价可采用降噪措施的减噪效果,是解决户内变电站噪声污染的关键问题。为此,综合声学有限元法(finite element method,FEM)求解复杂声场收敛性好及精度高的优点,及声学边界元法(boundary element method,BEM)降维求解大型声场的优势,提出了一种基于声学FEM-BEM的户内变电站噪声场求解算法。首先,建立变电站内部声源声固耦合模型,采用声学FEM求解混响噪声作用下的声固耦合响应;然后,基于声学FEM-BEM耦合理论,求解内、外耦合边界处结构单元受声固耦合激励产生的位移及应力载荷;最后,根据声压及应力载荷激发的外场声波扩散模型,基于常规Gauss数值积分法,建立外部空间声域2维BEM声学积分方程,求解外部声场。该算法在湖南某110 kV户内变电站噪声场的求解分析中得到了成功应用,与实测值的相对误差为3.61%~4.87%。展开更多
碎屑流是我国山区最危险的地质灾害之一,山区桥墩常受到碎屑流冲击而开裂、倾斜甚至倒塌,给山区桥梁建设、运营带来严重的安全隐患。采用离散元方法(discrete element method,DEM)和有限元方法(finite element method,FEM)耦合的三维数...碎屑流是我国山区最危险的地质灾害之一,山区桥墩常受到碎屑流冲击而开裂、倾斜甚至倒塌,给山区桥梁建设、运营带来严重的安全隐患。采用离散元方法(discrete element method,DEM)和有限元方法(finite element method,FEM)耦合的三维数值模拟方法模拟了碎屑流对双柱式桥墩的冲击效应,并结合斜槽试验,验证了耦合方法的准确性,进一步分析了碎屑流冲击坡度、距离和体积密度对桥墩冲击力的影响规律。结果表明,最大冲击力与碎屑流冲击坡度、距离和体积密度分别呈幂函数(指数大于1)、幂函数(指数小于1)和线性正相关。冲击坡度、距离和体积密度对最大冲击力的敏感度值分别为3.012、0.202、0.804,在桥梁碎屑流灾害防治时需重视冲击坡度和体积密度的影响。将冲击力的数值模拟值与流体动力学模型预测值对比分析表明,流体动力学模型理论公式能较好地预测桥墩所受的最大冲击力,最大预测误差低于23.6%。相关研究结果可为山区桥梁碎屑流灾害防治与设计提供一定的参考依据。展开更多
Traditional rigid body limit equilibrium method (RBLEM) was adopted for the stability evaluation and analysis of rock slope under earthquake scenario. It is not able to provide the real stress distribution of the st...Traditional rigid body limit equilibrium method (RBLEM) was adopted for the stability evaluation and analysis of rock slope under earthquake scenario. It is not able to provide the real stress distribution of the structure, while the strength reduction method relies on the arbitrary decision on the failure criteria. The dynamic limit equilibrium solution was proposed for the stability analysis of sliding block based on 3-D multi-grid method, by incorporating implicit stepping integration FEM. There are two independent meshes created in the analysis: One original 3-D FEM mesh is for the simulation of target structure and provides the stress time-history, while the other surface grid is for the simulation of sliding surface and could be selected and designed freely. As long as the stress time-history of the geotechnical structure under earthquake scenario is obtained based on 3-D nonlinear dynamic FEM analysis, the time-history of the force on sliding surface could be derived by projecting the stress time-history from 3-D FEM mesh to surface grid. After that, the safety factor time-history of the sliding block will be determined through applying limit equilibrium method. With those information in place, the structure's aseismatic stability ean be further studied. The above theory and method were also applied to the aseismatic stability analysis of Dagangshan arch dam's right bank high slope and compared with the the result generated by Quasi-static method. The comparative analysis reveals that the method not only raises the FEM's capability in accurate simulation of complicated geologic structure, but also increases the flexibility and comprehensiveness of limit equilibrium method. This method is reliable and recommended for further application in other real geotechnical engineering.展开更多
A three-dimensional dynamic damage model that fits both small and large damage sizes is developed to predict impact damage initiation and propagation for each lamina of T300-carbon/epoxy laminations.First,13 specimens...A three-dimensional dynamic damage model that fits both small and large damage sizes is developed to predict impact damage initiation and propagation for each lamina of T300-carbon/epoxy laminations.First,13 specimens of the same lamination sequence are subjected to three different impact energies(10 J,15 J,and 20 J).After the impact,the laminates are inspected by the naked eye to observe the damage in the outer layers,and subsequently X-rayed to detect the inner damage.Next,the stress analysis of laminates subjected to impact loading is presented,based on the Hertz contact law and virtual displacement principle.Based on the analysis results,a three-dimensional dynamic damage model is proposed,including the Hou failure criteria and Camanho stiffness degradation model,to predict the impact damage shape and area.The numerical predictions of the damage shape and area show a relatively reasonable agreement with the experiments.Finally,the impact damage initiation and propagation for each lamina are investigated using this damage model,and the results improve the understanding of the impact process.展开更多
The wave packet dynamics of I2^- anions is studied by using the time-dependent wave packet method. Two conclusions can be drawn from the calculations. First, the period of the total photoelectron signal oscillating wi...The wave packet dynamics of I2^- anions is studied by using the time-dependent wave packet method. Two conclusions can be drawn from the calculations. First, the period of the total photoelectron signal oscillating with the propagation of delay time is about 750fs. Second, the photoionization of I2^- anions begin at the time 600 fs, and the time needed for the population of the electronic state of I2 neutral molecule to reach the maximum becomes shorter with the increasing delay time.展开更多
In this study we experimentally reveal that the phase change mechanism can be selectively triggered by shaping femtosecond pulse trains based on electron dynamics control (EDC), including manipulation of excitations...In this study we experimentally reveal that the phase change mechanism can be selectively triggered by shaping femtosecond pulse trains based on electron dynamics control (EDC), including manipulation of excitations, ionizations, densities, and temperatures of electrons. By designing the pulse energy distribution to adjust the absorptions, excitations, ionizations, and recombinations of electrons, the dominant phase change mechanism experiences transition from nonthermal to thermal process. This phenomenon is observed in quadruple, triple, and double pulses per train ablation of fused silica separately. This opens up possibilities for controlling phase change mechanisms by EDC, which is of great significance in laser processing of dielectrics and fabrication of integrated nano- and micro-optical devices.展开更多
The ultrafast carrier relaxation processes in CdTe quantum dots are investigated by femtosecond fluorescence upconversion spectroscopy.Photo-excited hole relaxing to the edge of the forbidden gap takes a maximal time ...The ultrafast carrier relaxation processes in CdTe quantum dots are investigated by femtosecond fluorescence upconversion spectroscopy.Photo-excited hole relaxing to the edge of the forbidden gap takes a maximal time of ~ 1.6 ps with exciting at 400 nm,depending on the state of the photo-excited hole.The shallow trapped states and deep trap states in the forbidden gap are confirmed for CdTe quantum dots.In addition,Auger relaxation of trapped carriers is observed to occur with a time constant of ~ 5 ps.A schematic model of photodynamics is established based on the results of the spectroscopy studies.Our work demonstrates that femtosecond fluorescence up-conversion spectroscopy is a suitable and effective tool in studying the transportation and conversion dynamics of photon energy in a nanosystem.展开更多
Background: Internal fixation is appropriate for most intertrochanteric fractures. Optimal fixation is based on the stability of fracture. The mainstay of treatment of intertrochanteric fracture is fixation with a scr...Background: Internal fixation is appropriate for most intertrochanteric fractures. Optimal fixation is based on the stability of fracture. The mainstay of treatment of intertrochanteric fracture is fixation with a screw slide plate device or intramedullary device. So it is a matter of debate that which one is the best treatment, dynamic hip screw or proximal femoral nailing. Method: A prospective randomized and comparative study of 2 years duration was conducted on 60 patients admitted in the Department of Orthopedics in our hospital with intertrochanteric femur fracture. They were treated by a dynamic hip screw and proximal femoral nail. Patients were operated under image intensifier control. The parameters studied were functional outcome of Harris hip score, total duration of operation, rate of union, amount of collapse. These values were statistically evaluated and two tailed p-values were calculated and both groups were statistically compared. Result: The average age of our patient is 67.8 years. Among the fracture, 31% were stable, 58% were unstable, 11% were reverse oblique fracture. The average blood loss was 100 and 250 ml in PFN and DHS group, respectively. In PFN there was more no. of radiation exposure intraoperatively. The average operating time for the patients treated with PFN was 45 min as compared to 70 min in patients treated with DHS. The patients treated with PFN started early ambulation as they had better Harris Hip Score in the early period (at 1 and 3 months). In the long term both the implants had almost similar functional outcomes. Conclusion: In our study we have found that the unstable pattern was more common in old aged patients with higher grade of osteoporosis and PFN group has a better outcome in this unstable and osteoporotic fracture. PFN group has less blood loss and less operating time compared to DHS group. In PFN group patients have started early ambulation compared to DHS group.展开更多
A surface femtosecond two-photon photoemission (2PPE) spectrometer devoted to the study of ultrafast excited electron dynamics and photochemical kinetics on metal and metal oxide surfaces has been constructed. Low e...A surface femtosecond two-photon photoemission (2PPE) spectrometer devoted to the study of ultrafast excited electron dynamics and photochemical kinetics on metal and metal oxide surfaces has been constructed. Low energy photoelectrons are measured using a hemispherical electron energy analyzer with an imaging detector that allows us to detect the energy and the angular distributions of the photoelectrons simultaneously. A Mach-Zehnder interferom- eter was built for the time-resolved 2PPE (TR-2PPE) measurement to study ultrafast surface excited electron dynamics, which was demonstrated on the Cu(111) surface. A scheme for measuring time-dependent 2PPE (TD-2PPE) spectra has also been developed for studies of surface photochemistry. This technique has been applied to a preliminary study on the photochemical kinetics on ethanol/TiO2(110). We have also shown that the ultrafast dynamics of photoinduced surface excited resonances can be investigated in a reliable way by combining the TR-2PPE and TD-2PPE techniques.展开更多
3D dynamic analysis models of 1000 m deep-ocean mining pipeline, including steel lift pipe, pump, buffer and flexible hose, were established by finite element method (FEM). The coupling effect of steel lift pipe and f...3D dynamic analysis models of 1000 m deep-ocean mining pipeline, including steel lift pipe, pump, buffer and flexible hose, were established by finite element method (FEM). The coupling effect of steel lift pipe and flexible hose, and main external loads of pipeline were considered in the models, such as gravity, buoyancy, hydrodynamic forces, internal and external fluid pressures, concentrated suspension buoyancy on the flexible hose, torsional moment and axial force induced by pump working. Some relevant FEM models and solution techniques were developed, according to various 3D transient behaviors of integrated deep-ocean mining pipeline, including towing motions of track-keeping operation and launch process of pipeline. Meanwhile, an experimental verification system in towing water tank that had similar characteristics of designed mining pipeline was developed to verify the accuracy of the FEM models and dynamic simulation. The experiment results show that the experimental records and simulation results of stress of pipe are coincided. Based on the further simulations of 1 000 m deep-ocean mining pipeline, the simulation results show that, to form configuration of a saddle shape, the total concentrated suspension buoyancy of flexible hose should be 95%?105% of the gravity of flexible hose in water, the first suspension point occupies 1/3 of the total buoyancy, and the second suspension point occupies 2/3 of the total buoyancy. When towing velocity of mining system is less than 0.5 m/s, the towing track of buffer is coincided with the setting route of ship on the whole and the configuration of flexible hose is also kept well.展开更多
Rockslides are one of the most common geological hazards in mountainous areas and can pose significant threats to the safety of human lives and infrastructures. Studying the dynamic fragmentation process, and fragment...Rockslides are one of the most common geological hazards in mountainous areas and can pose significant threats to the safety of human lives and infrastructures. Studying the dynamic fragmentation process, and fragment characteristics of rock blocks during rockslides is of great significance. In this study,the influences of the slope angle on the dynamic fragmentation process, damage and energy evolution,and the fragments’ flying velocity and flying angle were systematically investigated using a coupled 3D FEM-DEM method. An improved fragment search algorithm was first proposed to more effectively extract the information of the fragments after impacting. The input parameters in the numerical modeling were carefully calibrated based on the quasi-static uniaxial compression tests and the rockimpact tests. The complex fragmentation process of rock block sliding along an inclined slope was simulated. The results indicate that the fragmentation intensity gradually increases with increasing the slope angle, and the fragmentation intensity of the front region of the rock block is always higher than that of the rear region. Additionally, the slope angle can significantly affect the damage ratio, energy dissipation, and the ratio of tensile crack to shear crack during the rockslides. The number of the fragments having higher flying velocities and larger flying angles increases with increasing the slope angle,which contributes to a larger spreading distance and a wider deposition area.展开更多
Based on existing algorithms, a newly developed contact search algorithm is proposed. The new algorithm consists of global search, local searching, local tracking and penetration calculation processes. It requires no ...Based on existing algorithms, a newly developed contact search algorithm is proposed. The new algorithm consists of global search, local searching, local tracking and penetration calculation processes. It requires no iteration steps. It can deal with not only general tool surfaces with vertical walls, but also tool surfaces meshed with elements having very poor aspect ratios. It is demonstrated that the FE code employing this new contact search algorithm becomes more reliable, efficient and accurate for sheet metal forming simulation than conventional ones.展开更多
The fast developing semiconductor industry is pushing to shrink and speed up transistors. This trend requires us to understand carrier dynamics in semiconductor heterojunctions with both high spatial and temporal reso...The fast developing semiconductor industry is pushing to shrink and speed up transistors. This trend requires us to understand carrier dynamics in semiconductor heterojunctions with both high spatial and temporal resolutions. Recently, we have successfully set up a timeresolved photoemission electron microscopy (TR-PEEM), which integrates the spectroscopic technique to measure electron densities at specific energy levels in space. This instrument provides us an unprecedented access to the evolution of electrons in terms of spatial location, time resolution, and energy, representing a new type of 4D spectro-microscopy. Here in this work, we present measurements of semiconductor performance with a time resolution of 184 fs, electron kinetic energy resolution of 150 meV, and spatial resolution of about 150 nm or better. We obtained time-resolved micro-area photoelectron spectra and energy-resolved TR-PEEM images on the Pb island on Si(111). These experimental results suggest that this instrument has the potential to be a powerful tool for investigating the carrier dynamics in various heterojunctions, which will deepen our understanding of semiconductor properties in the submicron/nanometer spatial scales and ultrafast time scales.展开更多
基金supported by the Swiss National Science Foundation(Grant No.189882)the National Natural Science Foundation of China(Grant No.41961134032)support provided by the New Investigator Award grant from the UK Engineering and Physical Sciences Research Council(Grant No.EP/V012169/1).
文摘In this study,we present a novel nodal integration-based particle finite element method(N-PFEM)designed for the dynamic analysis of saturated soils.Our approach incorporates the nodal integration technique into a generalised Hellinger-Reissner(HR)variational principle,creating an implicit PFEM formulation.To mitigate the volumetric locking issue in low-order elements,we employ a node-based strain smoothing technique.By discretising field variables at the centre of smoothing cells,we achieve nodal integration over cells,eliminating the need for sophisticated mapping operations after re-meshing in the PFEM.We express the discretised governing equations as a min-max optimisation problem,which is further reformulated as a standard second-order cone programming(SOCP)problem.Stresses,pore water pressure,and displacements are simultaneously determined using the advanced primal-dual interior point method.Consequently,our numerical model offers improved accuracy for stresses and pore water pressure compared to the displacement-based PFEM formulation.Numerical experiments demonstrate that the N-PFEM efficiently captures both transient and long-term hydro-mechanical behaviour of saturated soils with high accuracy,obviating the need for stabilisation or regularisation techniques commonly employed in other nodal integration-based PFEM approaches.This work holds significant implications for the development of robust and accurate numerical tools for studying saturated soil dynamics.
文摘BACKGROUND Among the most frequent hip fractures are trochanteric fractures,which usually occur from low-energy trauma like minor falls,especially in older people with osteoporotic bones.AIM To evaluate the treatment efficacy of dynamic condylar screws(DCS)and proximal femoral nails(PFN)for unstable intertrochanteric fractures.METHODS To find pertinent randomized controlled trials and retrospective observational studies comparing PFN with DCS for the management of unstable femoral intertrochanteric fractures,a thorough search was carried out.For research studies published between January 1996 and April 2024,PubMed,EMBASE,Scopus,Web of Science,Cochrane Library,and Google Scholar were all searched.The complete texts of the papers were retrieved,vetted,and independently examined by two investigators.Disputes were settled by consensus,and any disagreements that persisted were arbitrated by a third author.RESULTS This study included six articles,comprising a total of 173 patients.Compared to the DCS,the PFN had a shorter operation time[mean difference(MD):-41.7 min,95%confidence interval(95%CI):-63.04 to-20.35,P=0.0001],higher success rates with closed reduction techniques[risk ratio(RR):34.05,95%CI:11.12-104.31,P<0.00001],and required less intraoperative blood transfusion(MD:-1.4 units,95%CI:-1.80 to-1.00,P<0.00001).Additionally,the PFN showed shorter fracture union time(MD:-6.92 wk,95%CI:-10.27 to-3.57,P<0.0001)and a lower incidence of reoperation(RR:0.37,95%CI:0.17-0.82,P=0.01).However,there was no discernible variation regarding hospital stay,implant-related complications,and infections.CONCLUSION Compared to DCS,PFN offers shorter operative times,reduces the blood transfusions requirements,achieves higher closed reduction success,enables faster fracture healing,and lowers reoperation incidence.
文摘Traumatic brain injury(TBI)is a public health problem with an undue economic burden that impacts nearly every age,ethnic,and gender group across the globe(Capizzi et al.,2020).TBIs are often sustained during a dynamic range of exposures to energetic environmental forces and as such outcomes are typically heterogeneous regarding severity and pathology(Capizzi et al.,2020).
基金supported in part by Award 2121063 from National Science Foundation(to YM)AG66986 from the National Institutes of Health(to MSW).
文摘γ-Secretase,called“the proteasome of the membrane,”is a membrane-embedded protease complex that cleaves 150+peptide substrates with central roles in biology and medicine,including amyloid precursor protein and the Notch family of cell-surface receptors.Mutations inγ-secretase and amyloid precursor protein lead to early-onset familial Alzheimer’s disease.γ-Secretase has thus served as a critical drug target for treating familial Alzheimer’s disease and the more common late-onset Alzheimer’s disease as well.However,critical gaps remain in understanding the mechanisms of processive proteolysis of substrates,the effects of familial Alzheimer’s disease mutations,and allosteric modulation of substrate cleavage byγ-secretase.In this review,we focus on recent studies of structural dynamic mechanisms ofγ-secretase.Different mechanisms,including the“Fit-Stay-Trim,”“Sliding-Unwinding,”and“Tilting-Unwinding,”have been proposed for substrate proteolysis of amyloid precursor protein byγ-secretase based on all-atom molecular dynamics simulations.While an incorrect registry of the Notch1 substrate was identified in the cryo-electron microscopy structure of Notch1-boundγ-secretase,molecular dynamics simulations on a resolved model of Notch1-boundγ-secretase that was reconstructed using the amyloid precursor protein-boundγ-secretase as a template successfully capturedγ-secretase activation for proper cleavages of both wildtype and mutant Notch,being consistent with biochemical experimental findings.The approach could be potentially applied to decipher the processing mechanisms of various substrates byγ-secretase.In addition,controversy over the effects of familial Alzheimer’s disease mutations,particularly the issue of whether they stabilize or destabilizeγ-secretase-substrate complexes,is discussed.Finally,an outlook is provided for future studies ofγ-secretase,including pathways of substrate binding and product release,effects of modulators on familial Alzheimer’s disease mutations of theγ-secretase-substrate complexes.Comprehensive understanding of the functional mechanisms ofγ-secretase will greatly facilitate the rational design of effective drug molecules for treating familial Alzheimer’s disease and perhaps Alzheimer’s disease in general.
基金Project(51204003)supported by National Natural Science Foundation of ChinaProject(KJ2011A051)supported by the Scientific Research Foundation of Education Department of Anhui Province,China
文摘The microstructure simulation during the multi-pass hot rolling of AM50 alloy was studied by DEFORM-3D. The excellent agreement with the experiment observations shows that the present modeling and user routine are feasible for the reproduce of the hot rolling process. The multi-pass hot rolling contributes to the achievement of a uniformly recrystallized microstructure with fine grains in the rolled sheet. The sheet temperature before the finish rolling strongly affects the final grain size, but hardly affects the grain size distribution. This modeling and the user routine also have a potential to be applied in the researches of the other multi-pass hot deformation process.
文摘准确计算户内变电站大型、复杂的噪声场分布,进而评价可采用降噪措施的减噪效果,是解决户内变电站噪声污染的关键问题。为此,综合声学有限元法(finite element method,FEM)求解复杂声场收敛性好及精度高的优点,及声学边界元法(boundary element method,BEM)降维求解大型声场的优势,提出了一种基于声学FEM-BEM的户内变电站噪声场求解算法。首先,建立变电站内部声源声固耦合模型,采用声学FEM求解混响噪声作用下的声固耦合响应;然后,基于声学FEM-BEM耦合理论,求解内、外耦合边界处结构单元受声固耦合激励产生的位移及应力载荷;最后,根据声压及应力载荷激发的外场声波扩散模型,基于常规Gauss数值积分法,建立外部空间声域2维BEM声学积分方程,求解外部声场。该算法在湖南某110 kV户内变电站噪声场的求解分析中得到了成功应用,与实测值的相对误差为3.61%~4.87%。
文摘碎屑流是我国山区最危险的地质灾害之一,山区桥墩常受到碎屑流冲击而开裂、倾斜甚至倒塌,给山区桥梁建设、运营带来严重的安全隐患。采用离散元方法(discrete element method,DEM)和有限元方法(finite element method,FEM)耦合的三维数值模拟方法模拟了碎屑流对双柱式桥墩的冲击效应,并结合斜槽试验,验证了耦合方法的准确性,进一步分析了碎屑流冲击坡度、距离和体积密度对桥墩冲击力的影响规律。结果表明,最大冲击力与碎屑流冲击坡度、距离和体积密度分别呈幂函数(指数大于1)、幂函数(指数小于1)和线性正相关。冲击坡度、距离和体积密度对最大冲击力的敏感度值分别为3.012、0.202、0.804,在桥梁碎屑流灾害防治时需重视冲击坡度和体积密度的影响。将冲击力的数值模拟值与流体动力学模型预测值对比分析表明,流体动力学模型理论公式能较好地预测桥墩所受的最大冲击力,最大预测误差低于23.6%。相关研究结果可为山区桥梁碎屑流灾害防治与设计提供一定的参考依据。
基金Project(2013-KY-2) supported by the State Key Laboratory of Hydroscience and Engineering of Hydroscience, ChinaProject(50925931)supported by the National Funds for Distinguished Young Scientists, China
文摘Traditional rigid body limit equilibrium method (RBLEM) was adopted for the stability evaluation and analysis of rock slope under earthquake scenario. It is not able to provide the real stress distribution of the structure, while the strength reduction method relies on the arbitrary decision on the failure criteria. The dynamic limit equilibrium solution was proposed for the stability analysis of sliding block based on 3-D multi-grid method, by incorporating implicit stepping integration FEM. There are two independent meshes created in the analysis: One original 3-D FEM mesh is for the simulation of target structure and provides the stress time-history, while the other surface grid is for the simulation of sliding surface and could be selected and designed freely. As long as the stress time-history of the geotechnical structure under earthquake scenario is obtained based on 3-D nonlinear dynamic FEM analysis, the time-history of the force on sliding surface could be derived by projecting the stress time-history from 3-D FEM mesh to surface grid. After that, the safety factor time-history of the sliding block will be determined through applying limit equilibrium method. With those information in place, the structure's aseismatic stability ean be further studied. The above theory and method were also applied to the aseismatic stability analysis of Dagangshan arch dam's right bank high slope and compared with the the result generated by Quasi-static method. The comparative analysis reveals that the method not only raises the FEM's capability in accurate simulation of complicated geologic structure, but also increases the flexibility and comprehensiveness of limit equilibrium method. This method is reliable and recommended for further application in other real geotechnical engineering.
文摘A three-dimensional dynamic damage model that fits both small and large damage sizes is developed to predict impact damage initiation and propagation for each lamina of T300-carbon/epoxy laminations.First,13 specimens of the same lamination sequence are subjected to three different impact energies(10 J,15 J,and 20 J).After the impact,the laminates are inspected by the naked eye to observe the damage in the outer layers,and subsequently X-rayed to detect the inner damage.Next,the stress analysis of laminates subjected to impact loading is presented,based on the Hertz contact law and virtual displacement principle.Based on the analysis results,a three-dimensional dynamic damage model is proposed,including the Hou failure criteria and Camanho stiffness degradation model,to predict the impact damage shape and area.The numerical predictions of the damage shape and area show a relatively reasonable agreement with the experiments.Finally,the impact damage initiation and propagation for each lamina are investigated using this damage model,and the results improve the understanding of the impact process.
基金Supported by the National Natural Science Foundation of China under Grant No 10575017. The code used in our calculation is provided by Professor Ke-Li Han and we appreciate his help and kind advice.
文摘The wave packet dynamics of I2^- anions is studied by using the time-dependent wave packet method. Two conclusions can be drawn from the calculations. First, the period of the total photoelectron signal oscillating with the propagation of delay time is about 750fs. Second, the photoionization of I2^- anions begin at the time 600 fs, and the time needed for the population of the electronic state of I2 neutral molecule to reach the maximum becomes shorter with the increasing delay time.
基金Project supported by the National Basic Research Program of China (Grant No. 2011CB013000)the National Natural Science Foundation of China (Grant Nos. 90923039 and 51025521)
文摘In this study we experimentally reveal that the phase change mechanism can be selectively triggered by shaping femtosecond pulse trains based on electron dynamics control (EDC), including manipulation of excitations, ionizations, densities, and temperatures of electrons. By designing the pulse energy distribution to adjust the absorptions, excitations, ionizations, and recombinations of electrons, the dominant phase change mechanism experiences transition from nonthermal to thermal process. This phenomenon is observed in quadruple, triple, and double pulses per train ablation of fused silica separately. This opens up possibilities for controlling phase change mechanisms by EDC, which is of great significance in laser processing of dielectrics and fabrication of integrated nano- and micro-optical devices.
基金Project supported by the National Natural Science Foundation of China (Grant Nos. 11074003 and 20973001)the Key Program of Educational Commission of Anhui Province of China (Grant No. KJ2010A132)
文摘The ultrafast carrier relaxation processes in CdTe quantum dots are investigated by femtosecond fluorescence upconversion spectroscopy.Photo-excited hole relaxing to the edge of the forbidden gap takes a maximal time of ~ 1.6 ps with exciting at 400 nm,depending on the state of the photo-excited hole.The shallow trapped states and deep trap states in the forbidden gap are confirmed for CdTe quantum dots.In addition,Auger relaxation of trapped carriers is observed to occur with a time constant of ~ 5 ps.A schematic model of photodynamics is established based on the results of the spectroscopy studies.Our work demonstrates that femtosecond fluorescence up-conversion spectroscopy is a suitable and effective tool in studying the transportation and conversion dynamics of photon energy in a nanosystem.
文摘Background: Internal fixation is appropriate for most intertrochanteric fractures. Optimal fixation is based on the stability of fracture. The mainstay of treatment of intertrochanteric fracture is fixation with a screw slide plate device or intramedullary device. So it is a matter of debate that which one is the best treatment, dynamic hip screw or proximal femoral nailing. Method: A prospective randomized and comparative study of 2 years duration was conducted on 60 patients admitted in the Department of Orthopedics in our hospital with intertrochanteric femur fracture. They were treated by a dynamic hip screw and proximal femoral nail. Patients were operated under image intensifier control. The parameters studied were functional outcome of Harris hip score, total duration of operation, rate of union, amount of collapse. These values were statistically evaluated and two tailed p-values were calculated and both groups were statistically compared. Result: The average age of our patient is 67.8 years. Among the fracture, 31% were stable, 58% were unstable, 11% were reverse oblique fracture. The average blood loss was 100 and 250 ml in PFN and DHS group, respectively. In PFN there was more no. of radiation exposure intraoperatively. The average operating time for the patients treated with PFN was 45 min as compared to 70 min in patients treated with DHS. The patients treated with PFN started early ambulation as they had better Harris Hip Score in the early period (at 1 and 3 months). In the long term both the implants had almost similar functional outcomes. Conclusion: In our study we have found that the unstable pattern was more common in old aged patients with higher grade of osteoporosis and PFN group has a better outcome in this unstable and osteoporotic fracture. PFN group has less blood loss and less operating time compared to DHS group. In PFN group patients have started early ambulation compared to DHS group.
文摘A surface femtosecond two-photon photoemission (2PPE) spectrometer devoted to the study of ultrafast excited electron dynamics and photochemical kinetics on metal and metal oxide surfaces has been constructed. Low energy photoelectrons are measured using a hemispherical electron energy analyzer with an imaging detector that allows us to detect the energy and the angular distributions of the photoelectrons simultaneously. A Mach-Zehnder interferom- eter was built for the time-resolved 2PPE (TR-2PPE) measurement to study ultrafast surface excited electron dynamics, which was demonstrated on the Cu(111) surface. A scheme for measuring time-dependent 2PPE (TD-2PPE) spectra has also been developed for studies of surface photochemistry. This technique has been applied to a preliminary study on the photochemical kinetics on ethanol/TiO2(110). We have also shown that the ultrafast dynamics of photoinduced surface excited resonances can be investigated in a reliable way by combining the TR-2PPE and TD-2PPE techniques.
基金Project(DY105-3-2-2) supported by China Ocean Mineral Resources Research and Development Association(COMRA)Project(50675226) supported by the National Natural Science Foundation of China
文摘3D dynamic analysis models of 1000 m deep-ocean mining pipeline, including steel lift pipe, pump, buffer and flexible hose, were established by finite element method (FEM). The coupling effect of steel lift pipe and flexible hose, and main external loads of pipeline were considered in the models, such as gravity, buoyancy, hydrodynamic forces, internal and external fluid pressures, concentrated suspension buoyancy on the flexible hose, torsional moment and axial force induced by pump working. Some relevant FEM models and solution techniques were developed, according to various 3D transient behaviors of integrated deep-ocean mining pipeline, including towing motions of track-keeping operation and launch process of pipeline. Meanwhile, an experimental verification system in towing water tank that had similar characteristics of designed mining pipeline was developed to verify the accuracy of the FEM models and dynamic simulation. The experiment results show that the experimental records and simulation results of stress of pipe are coincided. Based on the further simulations of 1 000 m deep-ocean mining pipeline, the simulation results show that, to form configuration of a saddle shape, the total concentrated suspension buoyancy of flexible hose should be 95%?105% of the gravity of flexible hose in water, the first suspension point occupies 1/3 of the total buoyancy, and the second suspension point occupies 2/3 of the total buoyancy. When towing velocity of mining system is less than 0.5 m/s, the towing track of buffer is coincided with the setting route of ship on the whole and the configuration of flexible hose is also kept well.
基金supported by the National Natural Science Foundation of China (Grant Nos.52004182, 51908431)。
文摘Rockslides are one of the most common geological hazards in mountainous areas and can pose significant threats to the safety of human lives and infrastructures. Studying the dynamic fragmentation process, and fragment characteristics of rock blocks during rockslides is of great significance. In this study,the influences of the slope angle on the dynamic fragmentation process, damage and energy evolution,and the fragments’ flying velocity and flying angle were systematically investigated using a coupled 3D FEM-DEM method. An improved fragment search algorithm was first proposed to more effectively extract the information of the fragments after impacting. The input parameters in the numerical modeling were carefully calibrated based on the quasi-static uniaxial compression tests and the rockimpact tests. The complex fragmentation process of rock block sliding along an inclined slope was simulated. The results indicate that the fragmentation intensity gradually increases with increasing the slope angle, and the fragmentation intensity of the front region of the rock block is always higher than that of the rear region. Additionally, the slope angle can significantly affect the damage ratio, energy dissipation, and the ratio of tensile crack to shear crack during the rockslides. The number of the fragments having higher flying velocities and larger flying angles increases with increasing the slope angle,which contributes to a larger spreading distance and a wider deposition area.
基金the National Natural Science F oundation of China (5 9875 0 2 5 ) and Excellent Young Teacher Founda-tion of the Educational Departm ent of China
文摘Based on existing algorithms, a newly developed contact search algorithm is proposed. The new algorithm consists of global search, local searching, local tracking and penetration calculation processes. It requires no iteration steps. It can deal with not only general tool surfaces with vertical walls, but also tool surfaces meshed with elements having very poor aspect ratios. It is demonstrated that the FE code employing this new contact search algorithm becomes more reliable, efficient and accurate for sheet metal forming simulation than conventional ones.
基金supported by the National Key R&D Program (No.2018YFA0208700 and No.2016YFA0200602)the National Natural Science Foundation of China (No.21688102 and No.21403222)+1 种基金the Strategic Priority Research Program of the Chinese Academy of Sciences (No.XDB17000000)the Youth Innovation Promotion Association of Chinese Academy of Sciences (No.2017224)
文摘The fast developing semiconductor industry is pushing to shrink and speed up transistors. This trend requires us to understand carrier dynamics in semiconductor heterojunctions with both high spatial and temporal resolutions. Recently, we have successfully set up a timeresolved photoemission electron microscopy (TR-PEEM), which integrates the spectroscopic technique to measure electron densities at specific energy levels in space. This instrument provides us an unprecedented access to the evolution of electrons in terms of spatial location, time resolution, and energy, representing a new type of 4D spectro-microscopy. Here in this work, we present measurements of semiconductor performance with a time resolution of 184 fs, electron kinetic energy resolution of 150 meV, and spatial resolution of about 150 nm or better. We obtained time-resolved micro-area photoelectron spectra and energy-resolved TR-PEEM images on the Pb island on Si(111). These experimental results suggest that this instrument has the potential to be a powerful tool for investigating the carrier dynamics in various heterojunctions, which will deepen our understanding of semiconductor properties in the submicron/nanometer spatial scales and ultrafast time scales.