To better understand vertical air mass exchange driven by local circulation in the Himalayas, the volume flux of air mass is estimated in the Rongbuk Valley on the northern slope of Mount Everest, based on a volume cl...To better understand vertical air mass exchange driven by local circulation in the Himalayas, the volume flux of air mass is estimated in the Rongbuk Valley on the northern slope of Mount Everest, based on a volume closure method and wind-profiler measurements during the HEST2006 campaign in June 2006. Vertical air mass exchange was found to be dominated by a strong downward mass transfer from the late morning to late night. The average vertical air volume flux was 0.09 m s-1, which could be equivalent to a daily ventilation of 30 times the enclosed valley volume. This vertical air mass exchange process was greatly affected by the evolution of the South Asian summer monsoon (SASM), with a strong downward transfer during the SASM break stage, and a weak transfer during the SASM active stage.展开更多
For a better understanding of the air mass exchange processes between the surface and free atmos-phere in the Himalayas,a Himalayan exchange between the surface and troposphere 2007 (HEST2007) campaign was carried out...For a better understanding of the air mass exchange processes between the surface and free atmos-phere in the Himalayas,a Himalayan exchange between the surface and troposphere 2007 (HEST2007) campaign was carried out in the Rongbuk Valley,on the northern slope of Mt.Qomolangma,in June 2007.The wind,tem-perature and radiation conditions were measured during the campaign.Using these observation data,together with the National Centers for Environmental Prediction/the National Center for Atmospheric Research (NCEP/NCAR) reanalysis data,the air mass exchange between the inside of the valley and the outside of the valley is quantitatively estimated,based on a closed-valley method.The air mass is strongly injected into the Rongbuk Valley in the after-noon,which dominates the diurnal cycle,by a strong downward along-valley wind,with a maximum down-ward transfer rate of 9.4 cm s?1.The total air volume flux injected into the valley was 2.6×1011 m3 d?1 in 24 hours in June 2007,which is 15 times the total volume of the val-ley.The air mass transfer into the valley also exhibited a clear daily variation during the HEST2007 campaign,which can be affected by the synoptic situations through the adjustment of local radiation conditions.展开更多
The characteristics of the T/S structures,water mass exchange and deep circulation in the Andaman Sea are investigated based on the simulation from a high-resolution general circulation model(MITgcm).The results show ...The characteristics of the T/S structures,water mass exchange and deep circulation in the Andaman Sea are investigated based on the simulation from a high-resolution general circulation model(MITgcm).The results show that,below 1000 m,the water mass is saltier,warmer and more homogeneous in the Andaman Sea than that in the Bay of Bengal,attributing to the strong vertical mixing at the depth of^1800 m.The water mass exchange between the Andaman Sea and the Bay of Bengal goes through three major channels,which manifests itself as follows:the northern channel(Preparis Channel)is the main passage of water mass transport from the Bay of Bengal to the Andaman Sea,whereas the Middle Channel(the south of Andaman Islands and the north of Nicobar Islands)has an opposite transport;the southern channel(Great Channel)features with a four-layer water exchange which results in the least net transport among the three channels;all the transports through the three channels have an intra-annual variation with a period of half a year.At 1000-m depth,the entire Andaman Sea is occupied by a cyclonic circulation in January and July while by an anticyclonic one in April and October.The semiannual cycle found in both the deep circulation and water mass exchange is likely associated with the downwelling eastward-propagating Kelvin waves induced by the semiannual westerly component in the equatorial Indian Ocean during intermonsoon seasons.展开更多
We present a dynamic model of cavitation bubbles in a cluster,in which the effects of evaporation,condensation,and bubble-bubble interactions are taken into consideration.Under different ultrasound conditions,we exami...We present a dynamic model of cavitation bubbles in a cluster,in which the effects of evaporation,condensation,and bubble-bubble interactions are taken into consideration.Under different ultrasound conditions,we examine how the dynamics of cavitation bubbles are affected by several factors,such as the locations of the bubbles,the ambient radius,and the number of bubbles.Herein the variations of bubble radius,energy,temperature,pressure,and the quantity of vapor molecules are analyzed.Our findings reveal that bubble-bubble interactions can restrict the expansion of bubbles,reduce the exchange of energy among vapor molecules,and diminish the maximum internal temperature and pressure when bursting.The ambient radius of bubbles can influence the intensities of their oscillations,with clusters comprised of smaller bubbles creating optimal conditions for generating high-temperature and high-pressure regions.Moreover,an increase in the number of bubbles can further inhibit cavitation activities.The frequency,pressure and waveform of the driving wave can also exert a significant influence on cavitation activities,with rectangular waves enhancing and triangular waves weakening the cavitation of bubbles in the cluster.These results provide a theoretical basis for understanding the dynamics of cavitation bubbles in a bubble cluster,and the factors that affect their behaviors.展开更多
The marine dynamic environment of the Bohai Sea and the Yellow Sea in the winter of 2006 is simulated by the Regional Ocean Modelling System(ROMS) marine numerical model. Using the simulated temperature and salinity...The marine dynamic environment of the Bohai Sea and the Yellow Sea in the winter of 2006 is simulated by the Regional Ocean Modelling System(ROMS) marine numerical model. Using the simulated temperature and salinity, the water exchange zone between the Bohai Sea and Yellow Sea is defined through the Spectral Mixture Model(SMM). The influence of winter gales on the water exchange is also discussed. It is found that the Yellow Sea water masses in winter are distributed in a "tongue" shape in the Bohai Strait region, the water exchange zone presents a zonal distribution along the margin of the "tongue", with a tendency of running from northwest to southeast, and the water exchange is intensified at the tip of the "tongue". Besides, the coastal area in the northernmost Yellow Sea does not participate in the water exchange between the Bohai Sea and Yellow Sea. The result shows that the winter gale events play a role in enhancing the water exchange. It is specifically shown by the facts: the Yellow Sea warm current is enhanced to intrude the Bohai Sea by the gale process; the water exchange zone extends into the Bohai Sea; the water exchange belt in the southern part becomes wider; the mixture zone of river runoff with the Bohai Sea water upon its entry is enlarged and shifts northwards. Within two days after the gale process, the exchange zone retreats toward the Yellow Sea and the exchange zone resulted from the Huanghe River(Yellow River) runoff also shrinks back shoreward.展开更多
The article focuses on a theoretical and experimental framework for the quantification of interaction between nonlinear geomechnical and physicochemical processes in high-stress coal-bearing rock mass during mining un...The article focuses on a theoretical and experimental framework for the quantification of interaction between nonlinear geomechnical and physicochemical processes in high-stress coal-bearing rock mass during mining under high seismic risk due to large-scale blasting and earthquakes,as well as because of structural and temperature effects.The tests were aimed to examine and study comprehensively the piston mechanism of gas exchange and mass transfer processes,revealed recently at the Institute of Mining,SB RAS,as well as to explain the fact that the earthquake-induced low-velocity(quasi-meter range)pendulum waves(velocity to 1 m/s and frequency of 0.5–5 Hz)could stimulate an increase in the gas content in coal mines.In order to perform laboratory investigation at the Institute of Mining SB RAS,special-purpose stand for analyzing gas exchange and mass transfer processes in coal-bearing geomaterials under various thermodynamic conditions(P,V,T)and gas composition was constructed in cooperation with the Institute of Semiconductors Physics SB RAS.Matching of air flow rate with compression pressures allowed to obtain relations showing that air flow rate increases at the uncertain time interval under the increasing of the compression pressure.The same measurements was carried out with another gases such as Hydrogen H_(2),Helium He,methane CH_(4),carbon dioxide CO_(2) and carbon oxide CO.The laboratory tests aimed to detailed investigation of the previously revealed“piston mechanism”of gas exchange and mass transfer processes in the coal specimens and their quantitative description in terms of theory of the pendulum waves were carried in the first time.Consequently,there are some arguments for the testing of the opportunity of quantitative description of the“piston mechanism”related to gas exchange and mass transfer processes in the scale of coal mines.It is relevant when pendulum waves induced by powerful earthquakes and technical blasting reaches the mine.展开更多
Heat (energy), water (mass), and work (pres- sure) are the most fundamental utilities for operation units in chemical plants. To reduce energy consumption and diminish environment hazards, various integration me...Heat (energy), water (mass), and work (pres- sure) are the most fundamental utilities for operation units in chemical plants. To reduce energy consumption and diminish environment hazards, various integration methods have been developed. exchange networks (HENs), The application of heat mass exchange networks (MENs), water allocation heat exchange networks (WAHENs) and work exchange networks (WENs) have resulted in the significant saving of energy and water. This review presents the main works related to each network. The similarities and differences of these networks are also discussed. Through comparing and discussing these different networks, this review inspires researchers to propose more efficient and convenient methods for the design of existing exchange networks and even new types of networks including multi-objective networks for the system integration in order to enhance the optimization and controllability of processes.展开更多
n this paper,using NCEP dataset and the Wei's method,we calculate the exchange of mass across the thermal tropopause during 1998 over the Tibetan Plateau and its surroundings.The results indicate that:(1)There is ...n this paper,using NCEP dataset and the Wei's method,we calculate the exchange of mass across the thermal tropopause during 1998 over the Tibetan Plateau and its surroundings.The results indicate that:(1)There is strong air transport from troposphere to stratosphere in summer over the Tibetan Plateau and its surroundings.The air transport reaches the summit in midsummer with three large value centers among which the Bay of Bengal is the largest and the other two large centers lie in the east and northwest of the Tibetan Plateau,respectively.In May and October the cross-tropopause mass exchange reaches balance.In other months the mass transport is from stratosphere to troposphere.(2)As far as the cross-tropopause mass exchange from June to September in 1998 is concerned,the net mass transport is 13.7×10^(18) kg from troposphere to stratosphere,So the area from Tibetan Plateau to the Bay of Bengal is a channel through which air mass gets into stratosphere from troposphere.展开更多
Peptides can be potentmolecules with high efficacy and selectivity in the development of biotherapeutics.However,the poor pharmacokinetic properties of peptides pose major challenges for their broader medicinal applic...Peptides can be potentmolecules with high efficacy and selectivity in the development of biotherapeutics.However,the poor pharmacokinetic properties of peptides pose major challenges for their broader medicinal applications.Inspired by the proteinstabilizing role of natural N-glycosylation,we design and synthesize a series of parathyroid hormone(PTH)peptides(1-34),bearing either N-GlcNAc or biantennary complex-type N-glycan modification,and evaluate their serum stability and biological activities.The results indicate that an N-Asn-linked complex-type sialylundecasaccharide can increase the serum half-life and in vivo bioactivity of PTH peptides with a broad tolerance of modification sites.Further,hydrogen/deuterium exchange mass spectroscopy indicates that the larger-sized Nglycan can induce enhanced hydration dynamics in its surroundings,which may facilitate an improved resistance for the peptide against enzymatic proteolysis.This sialylundecasaccharide-based peptideengineering strategy has also been applied to glucagon-like peptide-1(7-37),leading to glycopeptides with enhanced hypoglycemic activity and acting time in vivo.Together,these results demonstrate the potential of using sialylated complextype N-glycan as a general engineering strategy for developing long-acting peptide therapeutics.展开更多
Uridine diphosphate-dependent glycosyltransferases(UGTs)mediate the glycosylation of plant metabolites,thereby altering their physicochemical properties and bioactivities.Plants possess numerous UGT genes,with the enc...Uridine diphosphate-dependent glycosyltransferases(UGTs)mediate the glycosylation of plant metabolites,thereby altering their physicochemical properties and bioactivities.Plants possess numerous UGT genes,with the encoded enzymes often glycosylating multiple substrates and some exhibiting substrate inhibition kinetics,but the biological function and molecular basis of these phenomena are not fully understood.The promiscuous monolignol/phytoalexin glycosyltransferase NbUGT72AY1 exhibits substrate inhibition(Ki)at 4 mM scopoletin,whereas the highly homologous monolignol StUGT72AY2 is inhibited at 190 mM.We therefore used hydrogen/deuterium exchange mass spectrometry and structure-based mutational analyses of both proteins and introduced NbUGT72AY1 residues into StUGT72AY2 and vice versa to study promiscuity and substrate inhibition of UGTs.A single F87I and chimeric mutant of NbUGT72AY1 showed significantly reducedscopoletin substrate inhibition,whereas its monolignolgly cosylation activity was almost unaffected.Reverse mutations in StUGT72AY2 resulted in increased scopoletin glycosylation,leading to enhanced promiscuity,which was accompanied by substrate inhibition.Studies of 3D structures identified open and closed UGT conformers,allowing visualization of the dynamics of conformational changes that occur during catalysis.Previously postulated substrate access tunnels likely serve as drainage channels.The results suggest a two-site model in which the second substrate molecule binds near the catalytic site and blocks product release.Mutational studies showed that minor changes in amino acid sequence can enhance the promiscuity of the enzyme and add new capabilities such as substrate inhibition without affecting existing functions.The proposed subfunctionalization mechanism of expanded promiscuity may play a role in enzyme evolution and highlights the importance of promiscuous enzymes in providing new functions.展开更多
A well-balanced Runge-Kutta discontinuous Galerkin method is presented for the numerical solution of multilayer shallow water equations with mass exchange and non-flat bottom topography.The governing equations are refo...A well-balanced Runge-Kutta discontinuous Galerkin method is presented for the numerical solution of multilayer shallow water equations with mass exchange and non-flat bottom topography.The governing equations are reformulated as a non-linear system of conservation laws with differential source forces and reaction terms.Coupling between theflow layers is accounted for in the system using a set of ex-change relations.The considered well-balanced Runge-Kutta discontinuous Galerkin method is a locally conservativefinite element method whose approximate solutions are discontinuous across the inter-element boundaries.The well-balanced property is achieved using a special discretization of source terms that depends on the nature of hydrostatic solutions along with the Gauss-Lobatto-Legendre nodes for the quadra-ture used in the approximation of source terms.The method can also be viewed as a high-order version of upwindfinite volume solvers and it offers attractive features for the numerical solution of conservation laws for which standardfinite element methods fail.To deal with the source terms we also implement a high-order splitting operator for the time integration.The accuracy of the proposed Runge-Kutta discontinuous Galerkin method is examined for several examples of multilayer free-surfaceflows over bothflat and non-flat beds.The performance of the method is also demonstrated by comparing the results obtained using the proposed method to those obtained using the incompressible hydrostatic Navier-Stokes equations and a well-established kinetic method.The proposed method is also applied to solve a recirculationflow problem in the Strait of Gibraltar.展开更多
基金financed by the Ministry of Science and Technology of the People’s Republic of China (Grant No2009CB421403)the Chinese Academy of Sciences(Grant Nos KZCX2-YW-Q11-01 and LAPC-KF-2008-12)
文摘To better understand vertical air mass exchange driven by local circulation in the Himalayas, the volume flux of air mass is estimated in the Rongbuk Valley on the northern slope of Mount Everest, based on a volume closure method and wind-profiler measurements during the HEST2006 campaign in June 2006. Vertical air mass exchange was found to be dominated by a strong downward mass transfer from the late morning to late night. The average vertical air volume flux was 0.09 m s-1, which could be equivalent to a daily ventilation of 30 times the enclosed valley volume. This vertical air mass exchange process was greatly affected by the evolution of the South Asian summer monsoon (SASM), with a strong downward transfer during the SASM break stage, and a weak transfer during the SASM active stage.
基金financed by the National Natural Science Foundation of China (Grant No.40533018)the Ministry of Science and Technology of the People’s Republic of China (Grant No.2009CB421403)the Chinese Academy of Sciences (Grant Nos.KZCX3-SW-231 and 8-070203)
文摘For a better understanding of the air mass exchange processes between the surface and free atmos-phere in the Himalayas,a Himalayan exchange between the surface and troposphere 2007 (HEST2007) campaign was carried out in the Rongbuk Valley,on the northern slope of Mt.Qomolangma,in June 2007.The wind,tem-perature and radiation conditions were measured during the campaign.Using these observation data,together with the National Centers for Environmental Prediction/the National Center for Atmospheric Research (NCEP/NCAR) reanalysis data,the air mass exchange between the inside of the valley and the outside of the valley is quantitatively estimated,based on a closed-valley method.The air mass is strongly injected into the Rongbuk Valley in the after-noon,which dominates the diurnal cycle,by a strong downward along-valley wind,with a maximum down-ward transfer rate of 9.4 cm s?1.The total air volume flux injected into the valley was 2.6×1011 m3 d?1 in 24 hours in June 2007,which is 15 times the total volume of the val-ley.The air mass transfer into the valley also exhibited a clear daily variation during the HEST2007 campaign,which can be affected by the synoptic situations through the adjustment of local radiation conditions.
基金The National Natural Science Foundation of China under contract Nos 41931182,41521005 and 41676016Guangdong Key Project under contract No.2019BT2H594+2 种基金the Key Special Project for Introduced Talents Team of Southern Marine Science and Engineering Guangdong Laboratory(Guangzhou)under contract Nos GML2019ZD0303 and GML2019ZD0304the Chinese Academy of Sciences under contract Nos ZDRW-XH-2019-2 and ISEE2018PY05the Independent Research Project Program of State Key Laboratory of Tropical Oceanography under contract Nos LTOZZ1902 and LTOZZ1802。
文摘The characteristics of the T/S structures,water mass exchange and deep circulation in the Andaman Sea are investigated based on the simulation from a high-resolution general circulation model(MITgcm).The results show that,below 1000 m,the water mass is saltier,warmer and more homogeneous in the Andaman Sea than that in the Bay of Bengal,attributing to the strong vertical mixing at the depth of^1800 m.The water mass exchange between the Andaman Sea and the Bay of Bengal goes through three major channels,which manifests itself as follows:the northern channel(Preparis Channel)is the main passage of water mass transport from the Bay of Bengal to the Andaman Sea,whereas the Middle Channel(the south of Andaman Islands and the north of Nicobar Islands)has an opposite transport;the southern channel(Great Channel)features with a four-layer water exchange which results in the least net transport among the three channels;all the transports through the three channels have an intra-annual variation with a period of half a year.At 1000-m depth,the entire Andaman Sea is occupied by a cyclonic circulation in January and July while by an anticyclonic one in April and October.The semiannual cycle found in both the deep circulation and water mass exchange is likely associated with the downwelling eastward-propagating Kelvin waves induced by the semiannual westerly component in the equatorial Indian Ocean during intermonsoon seasons.
基金Project supported by the National Natural Science Foundation of China (Grant No.12074354)。
文摘We present a dynamic model of cavitation bubbles in a cluster,in which the effects of evaporation,condensation,and bubble-bubble interactions are taken into consideration.Under different ultrasound conditions,we examine how the dynamics of cavitation bubbles are affected by several factors,such as the locations of the bubbles,the ambient radius,and the number of bubbles.Herein the variations of bubble radius,energy,temperature,pressure,and the quantity of vapor molecules are analyzed.Our findings reveal that bubble-bubble interactions can restrict the expansion of bubbles,reduce the exchange of energy among vapor molecules,and diminish the maximum internal temperature and pressure when bursting.The ambient radius of bubbles can influence the intensities of their oscillations,with clusters comprised of smaller bubbles creating optimal conditions for generating high-temperature and high-pressure regions.Moreover,an increase in the number of bubbles can further inhibit cavitation activities.The frequency,pressure and waveform of the driving wave can also exert a significant influence on cavitation activities,with rectangular waves enhancing and triangular waves weakening the cavitation of bubbles in the cluster.These results provide a theoretical basis for understanding the dynamics of cavitation bubbles in a bubble cluster,and the factors that affect their behaviors.
基金The National Natural Science Foundation of China under contract Nos 41206013,41376014,41430963 and41106004the Key Marine Science Foundation of the State Oceanic Administration of China for Young Scholar under contract Nos2012202,2013203 and 2012223+2 种基金the Public Science and Technology Research Funds Projects of Ocean under contract No.201205018the National Science and Technology Support Program under contract No.2014BAB12B02the Tianjin Science and Technology Support Program under contract No.14ZCZDSF00012
文摘The marine dynamic environment of the Bohai Sea and the Yellow Sea in the winter of 2006 is simulated by the Regional Ocean Modelling System(ROMS) marine numerical model. Using the simulated temperature and salinity, the water exchange zone between the Bohai Sea and Yellow Sea is defined through the Spectral Mixture Model(SMM). The influence of winter gales on the water exchange is also discussed. It is found that the Yellow Sea water masses in winter are distributed in a "tongue" shape in the Bohai Strait region, the water exchange zone presents a zonal distribution along the margin of the "tongue", with a tendency of running from northwest to southeast, and the water exchange is intensified at the tip of the "tongue". Besides, the coastal area in the northernmost Yellow Sea does not participate in the water exchange between the Bohai Sea and Yellow Sea. The result shows that the winter gale events play a role in enhancing the water exchange. It is specifically shown by the facts: the Yellow Sea warm current is enhanced to intrude the Bohai Sea by the gale process; the water exchange zone extends into the Bohai Sea; the water exchange belt in the southern part becomes wider; the mixture zone of river runoff with the Bohai Sea water upon its entry is enlarged and shifts northwards. Within two days after the gale process, the exchange zone retreats toward the Yellow Sea and the exchange zone resulted from the Huanghe River(Yellow River) runoff also shrinks back shoreward.
基金support of Russian Science Foundation (Project No.23-17-00148)as a part of R&D project (State registry No.121062200075-4).
文摘The article focuses on a theoretical and experimental framework for the quantification of interaction between nonlinear geomechnical and physicochemical processes in high-stress coal-bearing rock mass during mining under high seismic risk due to large-scale blasting and earthquakes,as well as because of structural and temperature effects.The tests were aimed to examine and study comprehensively the piston mechanism of gas exchange and mass transfer processes,revealed recently at the Institute of Mining,SB RAS,as well as to explain the fact that the earthquake-induced low-velocity(quasi-meter range)pendulum waves(velocity to 1 m/s and frequency of 0.5–5 Hz)could stimulate an increase in the gas content in coal mines.In order to perform laboratory investigation at the Institute of Mining SB RAS,special-purpose stand for analyzing gas exchange and mass transfer processes in coal-bearing geomaterials under various thermodynamic conditions(P,V,T)and gas composition was constructed in cooperation with the Institute of Semiconductors Physics SB RAS.Matching of air flow rate with compression pressures allowed to obtain relations showing that air flow rate increases at the uncertain time interval under the increasing of the compression pressure.The same measurements was carried out with another gases such as Hydrogen H_(2),Helium He,methane CH_(4),carbon dioxide CO_(2) and carbon oxide CO.The laboratory tests aimed to detailed investigation of the previously revealed“piston mechanism”of gas exchange and mass transfer processes in the coal specimens and their quantitative description in terms of theory of the pendulum waves were carried in the first time.Consequently,there are some arguments for the testing of the opportunity of quantitative description of the“piston mechanism”related to gas exchange and mass transfer processes in the scale of coal mines.It is relevant when pendulum waves induced by powerful earthquakes and technical blasting reaches the mine.
文摘Heat (energy), water (mass), and work (pres- sure) are the most fundamental utilities for operation units in chemical plants. To reduce energy consumption and diminish environment hazards, various integration methods have been developed. exchange networks (HENs), The application of heat mass exchange networks (MENs), water allocation heat exchange networks (WAHENs) and work exchange networks (WENs) have resulted in the significant saving of energy and water. This review presents the main works related to each network. The similarities and differences of these networks are also discussed. Through comparing and discussing these different networks, this review inspires researchers to propose more efficient and convenient methods for the design of existing exchange networks and even new types of networks including multi-objective networks for the system integration in order to enhance the optimization and controllability of processes.
文摘n this paper,using NCEP dataset and the Wei's method,we calculate the exchange of mass across the thermal tropopause during 1998 over the Tibetan Plateau and its surroundings.The results indicate that:(1)There is strong air transport from troposphere to stratosphere in summer over the Tibetan Plateau and its surroundings.The air transport reaches the summit in midsummer with three large value centers among which the Bay of Bengal is the largest and the other two large centers lie in the east and northwest of the Tibetan Plateau,respectively.In May and October the cross-tropopause mass exchange reaches balance.In other months the mass transport is from stratosphere to troposphere.(2)As far as the cross-tropopause mass exchange from June to September in 1998 is concerned,the net mass transport is 13.7×10^(18) kg from troposphere to stratosphere,So the area from Tibetan Plateau to the Bay of Bengal is a channel through which air mass gets into stratosphere from troposphere.
基金This research was made possible as a result of a generous grant from the Beijing National Science Foundation(grant no.JQ18024)the National Key R&D Program of China(grant no.2018YFA0507602)the National Natural Science Foundation of China(grant nos.91953111 and 91853113).
文摘Peptides can be potentmolecules with high efficacy and selectivity in the development of biotherapeutics.However,the poor pharmacokinetic properties of peptides pose major challenges for their broader medicinal applications.Inspired by the proteinstabilizing role of natural N-glycosylation,we design and synthesize a series of parathyroid hormone(PTH)peptides(1-34),bearing either N-GlcNAc or biantennary complex-type N-glycan modification,and evaluate their serum stability and biological activities.The results indicate that an N-Asn-linked complex-type sialylundecasaccharide can increase the serum half-life and in vivo bioactivity of PTH peptides with a broad tolerance of modification sites.Further,hydrogen/deuterium exchange mass spectroscopy indicates that the larger-sized Nglycan can induce enhanced hydration dynamics in its surroundings,which may facilitate an improved resistance for the peptide against enzymatic proteolysis.This sialylundecasaccharide-based peptideengineering strategy has also been applied to glucagon-like peptide-1(7-37),leading to glycopeptides with enhanced hypoglycemic activity and acting time in vivo.Together,these results demonstrate the potential of using sialylated complextype N-glycan as a general engineering strategy for developing long-acting peptide therapeutics.
文摘Uridine diphosphate-dependent glycosyltransferases(UGTs)mediate the glycosylation of plant metabolites,thereby altering their physicochemical properties and bioactivities.Plants possess numerous UGT genes,with the encoded enzymes often glycosylating multiple substrates and some exhibiting substrate inhibition kinetics,but the biological function and molecular basis of these phenomena are not fully understood.The promiscuous monolignol/phytoalexin glycosyltransferase NbUGT72AY1 exhibits substrate inhibition(Ki)at 4 mM scopoletin,whereas the highly homologous monolignol StUGT72AY2 is inhibited at 190 mM.We therefore used hydrogen/deuterium exchange mass spectrometry and structure-based mutational analyses of both proteins and introduced NbUGT72AY1 residues into StUGT72AY2 and vice versa to study promiscuity and substrate inhibition of UGTs.A single F87I and chimeric mutant of NbUGT72AY1 showed significantly reducedscopoletin substrate inhibition,whereas its monolignolgly cosylation activity was almost unaffected.Reverse mutations in StUGT72AY2 resulted in increased scopoletin glycosylation,leading to enhanced promiscuity,which was accompanied by substrate inhibition.Studies of 3D structures identified open and closed UGT conformers,allowing visualization of the dynamics of conformational changes that occur during catalysis.Previously postulated substrate access tunnels likely serve as drainage channels.The results suggest a two-site model in which the second substrate molecule binds near the catalytic site and blocks product release.Mutational studies showed that minor changes in amino acid sequence can enhance the promiscuity of the enzyme and add new capabilities such as substrate inhibition without affecting existing functions.The proposed subfunctionalization mechanism of expanded promiscuity may play a role in enzyme evolution and highlights the importance of promiscuous enzymes in providing new functions.
文摘A well-balanced Runge-Kutta discontinuous Galerkin method is presented for the numerical solution of multilayer shallow water equations with mass exchange and non-flat bottom topography.The governing equations are reformulated as a non-linear system of conservation laws with differential source forces and reaction terms.Coupling between theflow layers is accounted for in the system using a set of ex-change relations.The considered well-balanced Runge-Kutta discontinuous Galerkin method is a locally conservativefinite element method whose approximate solutions are discontinuous across the inter-element boundaries.The well-balanced property is achieved using a special discretization of source terms that depends on the nature of hydrostatic solutions along with the Gauss-Lobatto-Legendre nodes for the quadra-ture used in the approximation of source terms.The method can also be viewed as a high-order version of upwindfinite volume solvers and it offers attractive features for the numerical solution of conservation laws for which standardfinite element methods fail.To deal with the source terms we also implement a high-order splitting operator for the time integration.The accuracy of the proposed Runge-Kutta discontinuous Galerkin method is examined for several examples of multilayer free-surfaceflows over bothflat and non-flat beds.The performance of the method is also demonstrated by comparing the results obtained using the proposed method to those obtained using the incompressible hydrostatic Navier-Stokes equations and a well-established kinetic method.The proposed method is also applied to solve a recirculationflow problem in the Strait of Gibraltar.