The neutron spectrum unfolding by Bonner sphere spectrometer(BSS) is considered a complex multidimensional model,which requires complex mathematical methods to solve the first kind of Fredholm integral equation. In or...The neutron spectrum unfolding by Bonner sphere spectrometer(BSS) is considered a complex multidimensional model,which requires complex mathematical methods to solve the first kind of Fredholm integral equation. In order to solve the problem of the maximum likelihood expectation maximization(MLEM) algorithm which is easy to suffer the pitfalls of local optima and the particle swarm optimization(PSO) algorithm which is easy to get unreasonable flight direction and step length of particles, which leads to the invalid iteration and affect efficiency and accuracy, an improved PSO-MLEM algorithm, combined of PSO and MLEM algorithm, is proposed for neutron spectrum unfolding. The dynamic acceleration factor is used to balance the ability of global and local search, and improves the convergence speed and accuracy of the algorithm. Firstly, the Monte Carlo method was used to simulated the BSS to obtain the response function and count rates of BSS. In the simulation of count rate, four reference spectra from the IAEA Technical Report Series No. 403 were used as input parameters of the Monte Carlo method. The PSO-MLEM algorithm was used to unfold the neutron spectrum of the simulated data and was verified by the difference of the unfolded spectrum to the reference spectrum. Finally, the 252Cf neutron source was measured by BSS, and the PSO-MLEM algorithm was used to unfold the experimental neutron spectrum.Compared with maximum entropy deconvolution(MAXED), PSO and MLEM algorithm, the PSO-MLEM algorithm has fewer parameters and automatically adjusts the dynamic acceleration factor to solve the problem of local optima. The convergence speed of the PSO-MLEM algorithm is 1.4 times and 3.1 times that of the MLEM and PSO algorithms. Compared with PSO, MLEM and MAXED, the correlation coefficients of PSO-MLEM algorithm are increased by 33.1%, 33.5% and 1.9%, and the relative mean errors are decreased by 98.2%, 97.8% and 67.4%.展开更多
As modern weapons and equipment undergo increasing levels of informatization,intelligence,and networking,the topology and traffic characteristics of battlefield data networks built with tactical data links are becomin...As modern weapons and equipment undergo increasing levels of informatization,intelligence,and networking,the topology and traffic characteristics of battlefield data networks built with tactical data links are becoming progressively complex.In this paper,we employ a traffic matrix to model the tactical data link network.We propose a method that utilizes the Maximum Variance Unfolding(MVU)algorithm to conduct nonlinear dimensionality reduction analysis on high-dimensional open network traffic matrix datasets.This approach introduces novel ideas and methods for future applications,including traffic prediction and anomaly analysis in real battlefield network environments.展开更多
In an attempt to realize a flapping wing micro-air vehicle with morphing wings, we report on improvements to our previousfoldable artificial hind wing.Multiple hinges, which were implemented to mimic the bending zone ...In an attempt to realize a flapping wing micro-air vehicle with morphing wings, we report on improvements to our previousfoldable artificial hind wing.Multiple hinges, which were implemented to mimic the bending zone of a beetle hind wing, weremade of small composite hinge plates and tiny aluminum rivets.The buck-tails of rivets were flared after the hinge plates wereassembled with the rivets so that the folding/unfolding motions could be completed in less time, and the straight shape of theartificial hind wing could be maintained after fabrication.Folding and unfolding actions were triggered by electrically-activatedShape Memory Alloy (SMA) wires.For wing folding, the actuation characteristics of the SMA wire actuator were modifiedthrough heat treatment.Through a series of flapping tests, we confirmed that the artificial wings did not fold back and arbitrarilyfluctuate during the flapping motion.展开更多
Determining the similarity degree between process models was very important for their management,reuse,and analysis.Current approaches either focused on process model's structural aspect,or had inefficiency or imp...Determining the similarity degree between process models was very important for their management,reuse,and analysis.Current approaches either focused on process model's structural aspect,or had inefficiency or imprecision in behavioral similarity.Aiming at these problems,a novel similarity measure which extended an existing method named Transition Adjacent Relation(TAR) with improved precision and efficiency named TAR * was proposed.The ability of measuring similarity was extended by eliminating the duplicate tasks without impacting the behaviors.For precision,TARs was classified into repeatable and unrepeatable ones to identify whether a TAR was involved in a loop.Two new kinds of TARs were added,one related to the invisible tasks after the source place and before sink place,and the other representing implicit dependencies.For efficiency,all TARs based on unfolding instead of its reach ability graph of a labeled Petri net were calculated to avoid state space explosion.Experiments on artificial and real-world process models showed the effectiveness and efficiency of the proposed method.展开更多
A self-adaptive differential evolution neutron spectrum unfolding algorithm(SDENUA)is established in this study to unfold the neutron spectra obtained from a water-pumping-injection multilayered concentric sphere neut...A self-adaptive differential evolution neutron spectrum unfolding algorithm(SDENUA)is established in this study to unfold the neutron spectra obtained from a water-pumping-injection multilayered concentric sphere neutron spectrometer(WMNS).Specifically,the neutron fluence bounds are estimated to accelerate the algorithm convergence,and the minimum error between the optimal solution and input neutron counts with relative uncertainties is limited to 10^(-6)to avoid unnecessary calculations.Furthermore,the crossover probability and scaling factor are self-adaptively controlled.FLUKA Monte Carlo is used to simulate the readings of the WMNS under(1)a spectrum of Cf-252 and(2)its spectrum after being moderated,(3)a spectrum used for boron neutron capture therapy,and(4)a reactor spectrum.Subsequently,the measured neutron counts are unfolded using the SDENUA.The uncertainties of the measured neutron count and the response matrix are considered in the SDENUA,which does not require complex parameter tuning or an a priori default spectrum.The results indicate that the solutions of the SDENUA agree better with the IAEA spectra than those of MAXED and GRAVEL in UMG 3.1,and the errors of the final results calculated using the SDENUA are less than 12%.The established SDENUA can be used to unfold spectra from the WMNS.展开更多
Src SH3 protein domain is a typical two-state protein which has been confirmed by research of denaturant-induced unfolding dynamics.Force spectroscopy experiments by optical tweezers and atomic force microscopy have m...Src SH3 protein domain is a typical two-state protein which has been confirmed by research of denaturant-induced unfolding dynamics.Force spectroscopy experiments by optical tweezers and atomic force microscopy have measured the force-dependent unfolding rates with different kinds of pulling geometry.However,the equilibrium folding and unfolding dynamics at constant forces has not been reported.Here,using stable magnetic tweezers,we performed equilibrium folding and unfolding dynamic measurement and force-jump measurement of src SH3 domain with tethering points at its N-and C-termini.From the obtained force-dependent transition rates,a detailed two-state free energy landscape of src SH3 protein is constructed with quantitative information of folding free energy,transition state barrier height and position,which exemplifies the capability of magnetic tweezers to study protein folding and unfolding dynamics.展开更多
WT5”HZ]We introduced stability of arbitrary degree number for unfoldings of bifurcation problems and established the equivalence of three stabilities. Thom’s transversality theory is used to character the new stabil...WT5”HZ]We introduced stability of arbitrary degree number for unfoldings of bifurcation problems and established the equivalence of three stabilities. Thom’s transversality theory is used to character the new stability.[WT5HZ]展开更多
Rate splitting multiple access(RSMA)has shown great potentials for the next generation communication systems.In this work,we consider a two-user system in hybrid satellite terrestrial network(HSTN)where one of them is...Rate splitting multiple access(RSMA)has shown great potentials for the next generation communication systems.In this work,we consider a two-user system in hybrid satellite terrestrial network(HSTN)where one of them is heavily shadowed and the other uses cooperative RSMA to improve the transmission quality.The non-convex weighted sum rate(WSR)problem formulated based on this model is usually optimized by computational burdened weighted minimum mean square error(WMMSE)algorithm.We propose to apply deep unfolding to solve the optimization problem,which maps WMMSE iterations into a layer-wise network and could achieve better performance within limited iterations.We also incorporate momentum accelerated projection gradient descent(PGD)algorithm to circumvent the complicated operations in WMMSE that are not amenable for unfolding and mapping.The momentum and step size in deep unfolding network are selected as trainable parameters for training.As shown in the simulation results,deep unfolding scheme has WSR and convergence speed advantages over original WMMSE algorithm.展开更多
From the point of view of dynamics,the phenomenon of mode jumpingin the imperfect pitchfork problem is discussed.The dynamical mechanism of modeljumping of structures,such as plate and shell,that is brought about by t...From the point of view of dynamics,the phenomenon of mode jumpingin the imperfect pitchfork problem is discussed.The dynamical mechanism of modeljumping of structures,such as plate and shell,that is brought about by the extremurninstability,is explained.Finally,we give numerical simulation to show the validity ofour results.展开更多
The kinetic procedure of the unfolding of lysozyme induced by the reduction of disulfide was monitored by the time-resolved ESI-MS with a sheath liquid assistant electrospray interface. It was found that the reduction...The kinetic procedure of the unfolding of lysozyme induced by the reduction of disulfide was monitored by the time-resolved ESI-MS with a sheath liquid assistant electrospray interface. It was found that the reduction process for the eight disulfides had a less difference in the reaction time after denatured treatment. In addition, the alkylation of the reduced free thiols was much slower than the reduction procedure. An artifact peak produced by the CID fragmentation in the mass spectra was identified and the possible mechanism of the Hofmann elimination reaction was proposed.展开更多
An understanding of protein folding/unfolding processes has important implications for all biological processes, including protein degradation, protein translocation, aging, and diseases. All-atom molecular dynamics(M...An understanding of protein folding/unfolding processes has important implications for all biological processes, including protein degradation, protein translocation, aging, and diseases. All-atom molecular dynamics(MD) simulations are uniquely suitable for it because of their atomic level resolution and accuracy. However, limited by computational capabilities, nowadays even for small and fast-folding proteins, all-atom MD simulations of protein folding still presents a great challenge. An alternative way is to study unfolding process using MD simulations at high temperature. High temperature provides more energy to overcome energetic barriers to unfolding, and information obtained from studying unfolding can shed light on the mechanism of folding. In the present study, a 1000-ns MD simulation at high temperature(500 K)was performed to investigate the unfolding process of a small protein, chicken villin headpiece(HP-35). To infer the folding mechanism, a Markov state model was also built from our simulation, which maps out six macrostates during the folding/unfolding process as well as critical transitions between them, revealing the folding mechanism unambiguously.展开更多
α-catenin is an adhesion protein located at the cadherin-based cell-cell adherens junction.α-catenin cross-linksβ-catenin and actin fiber in the adhesion protein complex,and plays an important role in the formation...α-catenin is an adhesion protein located at the cadherin-based cell-cell adherens junction.α-catenin cross-linksβ-catenin and actin fiber in the adhesion protein complex,and plays an important role in the formation and modulation of cell-cell adhesion.The central modulation domains can be unfolded to expose binding site of vinculin when stretching force is applied.Here,we studied the force-induced unfolding dynamics ofα-catenin modulation domains under different loading rates from which the unfolding distance of M2 and M3 domains is determined to be 5-7 nm,and an unfolding intermediate state is identified.We also found that the folding process of M1-M3 domains goes through different pathways with cooperativity.展开更多
The review traces the unfolding of HIV epidemic in North India. The first few cases were reported in 1989 in Indians returning from African countries like Uganda, Zambia and a trickle from USA. Subsequently the cases ...The review traces the unfolding of HIV epidemic in North India. The first few cases were reported in 1989 in Indians returning from African countries like Uganda, Zambia and a trickle from USA. Subsequently the cases started pouring from coastal areas of Mumbai, Chennai and finally the virus spread all over through rail and road. In the North eastern region or the golden triangle, IV drug users formed a major group. Using a simple peptide ELISA, it was documented that the virus belonged to the NOF strain. This was much before clades were identified using molecular analysis. It appears that the HIV virus followed the drug (mandrax) route between Mumbai and South Africa. An alarming rise was observed among truck drivers fuelling HIV in Punjab villages who indulged in promiscuous behavior in road side making shift brothels near eating kiosks. Special customs in the state also flared the spread. During the early epidemic a very high prevalence was shown in blood transfused individuals (12.5%) which dropped to 2% -3% after aggressive measures taken by the NACO. While HIV positivity rates plateaued in some states by 2004, infection in Punjab continued to rise even after 2005. Kaposi sarcoma is almost unknown in Indian patients while TB and candida formed major co-infections. In one study, subtype V3 -V5 region chimeras of Indian clade C and clade B replicated freely in peripheral blood mononuclear cells (PBMC) and macrophages and showed higher HIV replication. Opt-out screening was started in an emergency setting in a tertiary care hospital. The positivity rate was 20/per thousand. Thus a large number of patients would have been missed if opt-out screening was not resorted to.展开更多
Populus simonii Carr., one of the main poplar tree species, is cultivated widely in Northeast and Northwest China in protection and timber forests. Plant phenology plays an important role in timber production by contr...Populus simonii Carr., one of the main poplar tree species, is cultivated widely in Northeast and Northwest China in protection and timber forests. Plant phenology plays an important role in timber production by controlling the growing period (i.e., the period between the leaf unfolding and the leaf turning yellow). It is important to understand this control mechanism and to improve the accuracy of the simulation of leaf unfolding phenology for P. simonii in order to determine accurately the timber production of P. simonii plantations. In this study, based on phenological observation data from 10 agricultural meteorological stations in Heilongjiang Province, China, model simulation was employed to determine the control mechanism of leaf unfolding of P. simonii. Furthermore, the predicting effects of nine phenology-simulating models for P. simonii leaf unfolding were evaluated and the distribution characteristics of P. simonii leaf unfolding in China in 2015 were simulated. The results show that P. simonii leaf unfolding is sensitive to air temperature;consequently, climate warming could advance the P. simonii leaf unfolding process. The phenological model based on air temperature could be better suited for simulating P. simonii leaf unfolding, with 76.7% of the calibration data of absolute error being less than three days. The performance of the models based solely on forcing requirements was found superior to that of the models incorporating chilling. If it was imperative that the chilling threshold is reached, the south of the Yunnan, Guangdong, and Guangxi provinces would be unsuitable for planting P. simonii. In this regard, the phenology model based on the chilling threshold as necessary condition was indicated a more reasonable model for the distribution characteristics of P. simonii leaf unfolding.展开更多
The technical feasibility of monitoring DNA melting and cooling transitions using a microcantilever substrate has been demonstrated and these results were compared with those measured in solution by circular dichroism...The technical feasibility of monitoring DNA melting and cooling transitions using a microcantilever substrate has been demonstrated and these results were compared with those measured in solution by circular dichroism. DNA hairpins have been immobilized on the surface of gold-coated microcantilever surfaces and their DNA melting and cooling transitions were monitored by nanomechanical deflections. The hairpins comprised of a 16 base-pair GACA repeat motif stem duplex with a 29 nucleotide variable region. Microcantilever deflection profiles, measured by the microcantilever response as a function of temperature, were unique to different hairpins indicative of the molecules’ general stability and denaturation characteristics. The major melting and cooling transition temperatures for all three immobilized oligonucleotides were between 41。C - 52。C. The composition and flexibility of the DNA stem loops were shown to influence the thermal transitions.展开更多
The reversible effect of microwave mediated denaturation of protein at low exposure time of 10 s has been demonstrated for the first time. The effect of microwave (2.45 GHz and 900 W) was confirmed in a homo-octameric...The reversible effect of microwave mediated denaturation of protein at low exposure time of 10 s has been demonstrated for the first time. The effect of microwave (2.45 GHz and 900 W) was confirmed in a homo-octameric alcohol oxidase in aqueous solution of pH 7.5. The unfolding events did not transverse through any intermediate states and no subunits of the protein were detached during the process. The refolding of the protein achieved at 4℃ for 24 h had regenerated the native enzyme. This reversible refolding approach excludes any chemical reagent and therefore established as simple technique for protein unfolding-folding studies.展开更多
基金supported by the National Natural science Foundation of China (No. 42127807)the Sichuan Science and Technology Program (No. 2020YJ0334)the Sichuan Science and Technology Breeding Program (No. 2022041)。
文摘The neutron spectrum unfolding by Bonner sphere spectrometer(BSS) is considered a complex multidimensional model,which requires complex mathematical methods to solve the first kind of Fredholm integral equation. In order to solve the problem of the maximum likelihood expectation maximization(MLEM) algorithm which is easy to suffer the pitfalls of local optima and the particle swarm optimization(PSO) algorithm which is easy to get unreasonable flight direction and step length of particles, which leads to the invalid iteration and affect efficiency and accuracy, an improved PSO-MLEM algorithm, combined of PSO and MLEM algorithm, is proposed for neutron spectrum unfolding. The dynamic acceleration factor is used to balance the ability of global and local search, and improves the convergence speed and accuracy of the algorithm. Firstly, the Monte Carlo method was used to simulated the BSS to obtain the response function and count rates of BSS. In the simulation of count rate, four reference spectra from the IAEA Technical Report Series No. 403 were used as input parameters of the Monte Carlo method. The PSO-MLEM algorithm was used to unfold the neutron spectrum of the simulated data and was verified by the difference of the unfolded spectrum to the reference spectrum. Finally, the 252Cf neutron source was measured by BSS, and the PSO-MLEM algorithm was used to unfold the experimental neutron spectrum.Compared with maximum entropy deconvolution(MAXED), PSO and MLEM algorithm, the PSO-MLEM algorithm has fewer parameters and automatically adjusts the dynamic acceleration factor to solve the problem of local optima. The convergence speed of the PSO-MLEM algorithm is 1.4 times and 3.1 times that of the MLEM and PSO algorithms. Compared with PSO, MLEM and MAXED, the correlation coefficients of PSO-MLEM algorithm are increased by 33.1%, 33.5% and 1.9%, and the relative mean errors are decreased by 98.2%, 97.8% and 67.4%.
文摘As modern weapons and equipment undergo increasing levels of informatization,intelligence,and networking,the topology and traffic characteristics of battlefield data networks built with tactical data links are becoming progressively complex.In this paper,we employ a traffic matrix to model the tactical data link network.We propose a method that utilizes the Maximum Variance Unfolding(MVU)algorithm to conduct nonlinear dimensionality reduction analysis on high-dimensional open network traffic matrix datasets.This approach introduces novel ideas and methods for future applications,including traffic prediction and anomaly analysis in real battlefield network environments.
基金supported by the Korea Science and Engineering Foundation Grant(National Research Laboratory Program,R0A-2007-000-200012-0)the Korea Research Foundation(KRF-006-005-J03301)partially supported by the 2009 KU Brain Pool of Konkuk University
文摘In an attempt to realize a flapping wing micro-air vehicle with morphing wings, we report on improvements to our previousfoldable artificial hind wing.Multiple hinges, which were implemented to mimic the bending zone of a beetle hind wing, weremade of small composite hinge plates and tiny aluminum rivets.The buck-tails of rivets were flared after the hinge plates wereassembled with the rivets so that the folding/unfolding motions could be completed in less time, and the straight shape of theartificial hind wing could be maintained after fabrication.Folding and unfolding actions were triggered by electrically-activatedShape Memory Alloy (SMA) wires.For wing folding, the actuation characteristics of the SMA wire actuator were modifiedthrough heat treatment.Through a series of flapping tests, we confirmed that the artificial wings did not fold back and arbitrarilyfluctuate during the flapping motion.
基金Project supported by the National Science Foundation,China(No.61003099)the National Basic Research Program,China(No.2009CB320700)
文摘Determining the similarity degree between process models was very important for their management,reuse,and analysis.Current approaches either focused on process model's structural aspect,or had inefficiency or imprecision in behavioral similarity.Aiming at these problems,a novel similarity measure which extended an existing method named Transition Adjacent Relation(TAR) with improved precision and efficiency named TAR * was proposed.The ability of measuring similarity was extended by eliminating the duplicate tasks without impacting the behaviors.For precision,TARs was classified into repeatable and unrepeatable ones to identify whether a TAR was involved in a loop.Two new kinds of TARs were added,one related to the invisible tasks after the source place and before sink place,and the other representing implicit dependencies.For efficiency,all TARs based on unfolding instead of its reach ability graph of a labeled Petri net were calculated to avoid state space explosion.Experiments on artificial and real-world process models showed the effectiveness and efficiency of the proposed method.
基金supported by the National Key R&D Program of the MOST of China(No.2016YFA0300204)the National Natural Science Foundation of China(Nos.11227902)as part of the Si PáME2beamline project+1 种基金supported by the National Natural Science Foundation of China(No.41774120)the Sichuan Science and Technology Program(No.2021YJ0329)。
文摘A self-adaptive differential evolution neutron spectrum unfolding algorithm(SDENUA)is established in this study to unfold the neutron spectra obtained from a water-pumping-injection multilayered concentric sphere neutron spectrometer(WMNS).Specifically,the neutron fluence bounds are estimated to accelerate the algorithm convergence,and the minimum error between the optimal solution and input neutron counts with relative uncertainties is limited to 10^(-6)to avoid unnecessary calculations.Furthermore,the crossover probability and scaling factor are self-adaptively controlled.FLUKA Monte Carlo is used to simulate the readings of the WMNS under(1)a spectrum of Cf-252 and(2)its spectrum after being moderated,(3)a spectrum used for boron neutron capture therapy,and(4)a reactor spectrum.Subsequently,the measured neutron counts are unfolded using the SDENUA.The uncertainties of the measured neutron count and the response matrix are considered in the SDENUA,which does not require complex parameter tuning or an a priori default spectrum.The results indicate that the solutions of the SDENUA agree better with the IAEA spectra than those of MAXED and GRAVEL in UMG 3.1,and the errors of the final results calculated using the SDENUA are less than 12%.The established SDENUA can be used to unfold spectra from the WMNS.
基金the National Natural Science Foundation of China(Grant Nos.11874309 and 11474237)the 111 Project(Grant No.B16029)。
文摘Src SH3 protein domain is a typical two-state protein which has been confirmed by research of denaturant-induced unfolding dynamics.Force spectroscopy experiments by optical tweezers and atomic force microscopy have measured the force-dependent unfolding rates with different kinds of pulling geometry.However,the equilibrium folding and unfolding dynamics at constant forces has not been reported.Here,using stable magnetic tweezers,we performed equilibrium folding and unfolding dynamic measurement and force-jump measurement of src SH3 domain with tethering points at its N-and C-termini.From the obtained force-dependent transition rates,a detailed two-state free energy landscape of src SH3 protein is constructed with quantitative information of folding free energy,transition state barrier height and position,which exemplifies the capability of magnetic tweezers to study protein folding and unfolding dynamics.
基金Supported by the National Natural Science Foundation of China(198710 74)
文摘WT5”HZ]We introduced stability of arbitrary degree number for unfoldings of bifurcation problems and established the equivalence of three stabilities. Thom’s transversality theory is used to character the new stability.[WT5HZ]
基金sponsored by National Natural Science Foundation of China (No. 61871422, No.62027801)
文摘Rate splitting multiple access(RSMA)has shown great potentials for the next generation communication systems.In this work,we consider a two-user system in hybrid satellite terrestrial network(HSTN)where one of them is heavily shadowed and the other uses cooperative RSMA to improve the transmission quality.The non-convex weighted sum rate(WSR)problem formulated based on this model is usually optimized by computational burdened weighted minimum mean square error(WMMSE)algorithm.We propose to apply deep unfolding to solve the optimization problem,which maps WMMSE iterations into a layer-wise network and could achieve better performance within limited iterations.We also incorporate momentum accelerated projection gradient descent(PGD)algorithm to circumvent the complicated operations in WMMSE that are not amenable for unfolding and mapping.The momentum and step size in deep unfolding network are selected as trainable parameters for training.As shown in the simulation results,deep unfolding scheme has WSR and convergence speed advantages over original WMMSE algorithm.
基金This work is supported by the Foundation of the National Educational Committeeand the National Natural Sciences Foundation of China.
文摘From the point of view of dynamics,the phenomenon of mode jumpingin the imperfect pitchfork problem is discussed.The dynamical mechanism of modeljumping of structures,such as plate and shell,that is brought about by the extremurninstability,is explained.Finally,we give numerical simulation to show the validity ofour results.
基金NFS of China(No.29927002)and Visiting Scholar Foundation of Key Lab. in University.
文摘The kinetic procedure of the unfolding of lysozyme induced by the reduction of disulfide was monitored by the time-resolved ESI-MS with a sheath liquid assistant electrospray interface. It was found that the reduction process for the eight disulfides had a less difference in the reaction time after denatured treatment. In addition, the alkylation of the reduced free thiols was much slower than the reduction procedure. An artifact peak produced by the CID fragmentation in the mass spectra was identified and the possible mechanism of the Hofmann elimination reaction was proposed.
基金Project supported by the National Natural Science Foundation of China(Grant Nos.11175068 and 11474117)the Self-determined Research Funds of CCNU from the Colleges Basic Research and Operation of MOE,China(Grant No.230-20205170054)
文摘An understanding of protein folding/unfolding processes has important implications for all biological processes, including protein degradation, protein translocation, aging, and diseases. All-atom molecular dynamics(MD) simulations are uniquely suitable for it because of their atomic level resolution and accuracy. However, limited by computational capabilities, nowadays even for small and fast-folding proteins, all-atom MD simulations of protein folding still presents a great challenge. An alternative way is to study unfolding process using MD simulations at high temperature. High temperature provides more energy to overcome energetic barriers to unfolding, and information obtained from studying unfolding can shed light on the mechanism of folding. In the present study, a 1000-ns MD simulation at high temperature(500 K)was performed to investigate the unfolding process of a small protein, chicken villin headpiece(HP-35). To infer the folding mechanism, a Markov state model was also built from our simulation, which maps out six macrostates during the folding/unfolding process as well as critical transitions between them, revealing the folding mechanism unambiguously.
基金the National Nature Science Foundation of China(Grant Nos.11474237 and 11574310)the 111 Project(Grant No.B16029).
文摘α-catenin is an adhesion protein located at the cadherin-based cell-cell adherens junction.α-catenin cross-linksβ-catenin and actin fiber in the adhesion protein complex,and plays an important role in the formation and modulation of cell-cell adhesion.The central modulation domains can be unfolded to expose binding site of vinculin when stretching force is applied.Here,we studied the force-induced unfolding dynamics ofα-catenin modulation domains under different loading rates from which the unfolding distance of M2 and M3 domains is determined to be 5-7 nm,and an unfolding intermediate state is identified.We also found that the folding process of M1-M3 domains goes through different pathways with cooperativity.
文摘The review traces the unfolding of HIV epidemic in North India. The first few cases were reported in 1989 in Indians returning from African countries like Uganda, Zambia and a trickle from USA. Subsequently the cases started pouring from coastal areas of Mumbai, Chennai and finally the virus spread all over through rail and road. In the North eastern region or the golden triangle, IV drug users formed a major group. Using a simple peptide ELISA, it was documented that the virus belonged to the NOF strain. This was much before clades were identified using molecular analysis. It appears that the HIV virus followed the drug (mandrax) route between Mumbai and South Africa. An alarming rise was observed among truck drivers fuelling HIV in Punjab villages who indulged in promiscuous behavior in road side making shift brothels near eating kiosks. Special customs in the state also flared the spread. During the early epidemic a very high prevalence was shown in blood transfused individuals (12.5%) which dropped to 2% -3% after aggressive measures taken by the NACO. While HIV positivity rates plateaued in some states by 2004, infection in Punjab continued to rise even after 2005. Kaposi sarcoma is almost unknown in Indian patients while TB and candida formed major co-infections. In one study, subtype V3 -V5 region chimeras of Indian clade C and clade B replicated freely in peripheral blood mononuclear cells (PBMC) and macrophages and showed higher HIV replication. Opt-out screening was started in an emergency setting in a tertiary care hospital. The positivity rate was 20/per thousand. Thus a large number of patients would have been missed if opt-out screening was not resorted to.
文摘Populus simonii Carr., one of the main poplar tree species, is cultivated widely in Northeast and Northwest China in protection and timber forests. Plant phenology plays an important role in timber production by controlling the growing period (i.e., the period between the leaf unfolding and the leaf turning yellow). It is important to understand this control mechanism and to improve the accuracy of the simulation of leaf unfolding phenology for P. simonii in order to determine accurately the timber production of P. simonii plantations. In this study, based on phenological observation data from 10 agricultural meteorological stations in Heilongjiang Province, China, model simulation was employed to determine the control mechanism of leaf unfolding of P. simonii. Furthermore, the predicting effects of nine phenology-simulating models for P. simonii leaf unfolding were evaluated and the distribution characteristics of P. simonii leaf unfolding in China in 2015 were simulated. The results show that P. simonii leaf unfolding is sensitive to air temperature;consequently, climate warming could advance the P. simonii leaf unfolding process. The phenological model based on air temperature could be better suited for simulating P. simonii leaf unfolding, with 76.7% of the calibration data of absolute error being less than three days. The performance of the models based solely on forcing requirements was found superior to that of the models incorporating chilling. If it was imperative that the chilling threshold is reached, the south of the Yunnan, Guangdong, and Guangxi provinces would be unsuitable for planting P. simonii. In this regard, the phenology model based on the chilling threshold as necessary condition was indicated a more reasonable model for the distribution characteristics of P. simonii leaf unfolding.
文摘The technical feasibility of monitoring DNA melting and cooling transitions using a microcantilever substrate has been demonstrated and these results were compared with those measured in solution by circular dichroism. DNA hairpins have been immobilized on the surface of gold-coated microcantilever surfaces and their DNA melting and cooling transitions were monitored by nanomechanical deflections. The hairpins comprised of a 16 base-pair GACA repeat motif stem duplex with a 29 nucleotide variable region. Microcantilever deflection profiles, measured by the microcantilever response as a function of temperature, were unique to different hairpins indicative of the molecules’ general stability and denaturation characteristics. The major melting and cooling transition temperatures for all three immobilized oligonucleotides were between 41。C - 52。C. The composition and flexibility of the DNA stem loops were shown to influence the thermal transitions.
文摘The reversible effect of microwave mediated denaturation of protein at low exposure time of 10 s has been demonstrated for the first time. The effect of microwave (2.45 GHz and 900 W) was confirmed in a homo-octameric alcohol oxidase in aqueous solution of pH 7.5. The unfolding events did not transverse through any intermediate states and no subunits of the protein were detached during the process. The refolding of the protein achieved at 4℃ for 24 h had regenerated the native enzyme. This reversible refolding approach excludes any chemical reagent and therefore established as simple technique for protein unfolding-folding studies.