In early of 1960s, I was a graduate student studying on tRNA biochemistry. In the course of the research, the magnesium ions stabilized the tertiary structure of tRNA, resulting in its resistance to enzymatic degradat...In early of 1960s, I was a graduate student studying on tRNA biochemistry. In the course of the research, the magnesium ions stabilized the tertiary structure of tRNA, resulting in its resistance to enzymatic degradation was discovered independently. The experiment of deaminated (denatured) tRNA obtained from native tRNA was designed and conducted and further proved the validity of this finding. It was found that magnesium ions could stabilize the tertiary structure of the natrive tRNA but could not stabilize structure of the deaminated tRNA. In term of the methodology, this stabilization technique has been widely applied in sequencing analysis of RNA and has greatly promoted the progress in the study of primary structure of RNA. More importantly, the stabilization of the tertiary structure of RNA by magnesium ions plays a key role both in the processing of messenger RNAs and the ribozyme activity. After our first article in Chinese was published in 1963, a paper of Nishimura & Novelli came into our note. The received date of their paper was March 22 of 1963, only 4 days earlier than that of our first paper. Thus, we and Nishimura & Novelli made almost at the same time the earliest discovery of the role of magnesium ions on stabilizing the tertiary structure of the transfer RNA and thus resulted in resistance of tRNA degradation by enzymes. However, this discovery was not initially appreciated for a period of time but was finally “visualized” and proved by X-ray crystal structure of yeast phenylalanine tRNA, which has provided more accurate information on the geometry of the magnesium-binding sites in tRNA.展开更多
We have developed a new 3D multi-physics multi-material code, ALE-AMR, which combines Arbitrary Lagrangian Eulerian (ALE) hydrodynamics with Adaptive Mesh Refinement (AMR) to connect the continuum to the microstru...We have developed a new 3D multi-physics multi-material code, ALE-AMR, which combines Arbitrary Lagrangian Eulerian (ALE) hydrodynamics with Adaptive Mesh Refinement (AMR) to connect the continuum to the microstructural regimes. The code is unique in its ability to model hot radiating plasmas and cold fragmenting solids. New numerical techniques were developed for many of the physics packages to work efficiently on a dynamically moving and adapting mesh. We use interface reconstruction based on volume fractions of the material components within mixed zones and reconstruct interfaces as needed. This interface reconstruction model is also used for void coalescence and fragmentation. A flexible strength/failure framework allows for pluggable material models, which may require material history arrays to determine the level of accumulated damage or the evolving yield stress in J2 plasticity models. For some applications laser rays are propagating through a virtual composite mesh consisting of the finest resolution representation of the modeled space. A new 2nd order accurate diffusion solver has been implemented for the thermal conduction and radiation transport packages. One application area is the modeling of laser/target effects including debris/shrapnel generation. Other application areas include warm dense matter, EUV lithography, and material wall interactions for fusion devices.展开更多
IgA nephropathy(IgAN)is a leading cause of chronic kidney disease(CKD),which are commonly accompanied by dyslipidemia.Obesity is also associated with dyslipidemia and risk of CKD,but the relation of the dyslipidemia p...IgA nephropathy(IgAN)is a leading cause of chronic kidney disease(CKD),which are commonly accompanied by dyslipidemia.Obesity is also associated with dyslipidemia and risk of CKD,but the relation of the dyslipidemia patterns with obesity and disease progression in IgAN patients remains unknown.Traditional Chinese medicine(TCM)and the combined treatment with corticosteroids and TCM have been shown to be of benefit for IgAN patients,but predictive markers for guiding these treatments are lacking.Here,we quantified 545 lipid species in the plasma from 196 participants,including 140 IgAN patients and 56 healthy volunteers,and revealed an altered plasma lipidome in IgAN patients as compared to healthy participants.Association analysis showed that a subgroup of glycerides,particularly triacylglycerols(TGs)containing docosahexaenoic acid,were positively associated with high body mass index(BMI)in under-or normal-weight IgAN patients,while several free fatty acids and sphingomyelins were positively associated with high BMI in overweight or obese IgAN patients.Further,our study suggested that elevated levels of eight lipids,mainly TG species containing linolenic acid,were independent risk factors for IgAN progression and also reported the prospective association of circulating lipids with treatment outcomes in IgAN.Taken together,our findings may not only help to achieve precision medicine but also provide a knowledge base for dietary intervention in the treatment of IgAN.展开更多
文摘In early of 1960s, I was a graduate student studying on tRNA biochemistry. In the course of the research, the magnesium ions stabilized the tertiary structure of tRNA, resulting in its resistance to enzymatic degradation was discovered independently. The experiment of deaminated (denatured) tRNA obtained from native tRNA was designed and conducted and further proved the validity of this finding. It was found that magnesium ions could stabilize the tertiary structure of the natrive tRNA but could not stabilize structure of the deaminated tRNA. In term of the methodology, this stabilization technique has been widely applied in sequencing analysis of RNA and has greatly promoted the progress in the study of primary structure of RNA. More importantly, the stabilization of the tertiary structure of RNA by magnesium ions plays a key role both in the processing of messenger RNAs and the ribozyme activity. After our first article in Chinese was published in 1963, a paper of Nishimura & Novelli came into our note. The received date of their paper was March 22 of 1963, only 4 days earlier than that of our first paper. Thus, we and Nishimura & Novelli made almost at the same time the earliest discovery of the role of magnesium ions on stabilizing the tertiary structure of the transfer RNA and thus resulted in resistance of tRNA degradation by enzymes. However, this discovery was not initially appreciated for a period of time but was finally “visualized” and proved by X-ray crystal structure of yeast phenylalanine tRNA, which has provided more accurate information on the geometry of the magnesium-binding sites in tRNA.
基金the National Energy Research Scientific Computing Center,a DOE Office of Science User Facility supported by the Office of Science,U. S.Department of Energy under Contract No.DEAC02-05CH11231LBNL under DE-AC0205CH11231 was supported by the Director,Office of Science of the U.S.Department of Energy and the Petascale Initiative in Computational Science and Engineering+1 种基金LLNL was performed under the auspices of the U.S.Department of Energy by Lawrence Livermore National Security,LLC,Lawrence Livermore National Laboratory under Contract DE-AC5207NA27344UCLA and LLNL acknowledge UC Lab Fees Research Grant 09-LR-04-116741-BERA
文摘We have developed a new 3D multi-physics multi-material code, ALE-AMR, which combines Arbitrary Lagrangian Eulerian (ALE) hydrodynamics with Adaptive Mesh Refinement (AMR) to connect the continuum to the microstructural regimes. The code is unique in its ability to model hot radiating plasmas and cold fragmenting solids. New numerical techniques were developed for many of the physics packages to work efficiently on a dynamically moving and adapting mesh. We use interface reconstruction based on volume fractions of the material components within mixed zones and reconstruct interfaces as needed. This interface reconstruction model is also used for void coalescence and fragmentation. A flexible strength/failure framework allows for pluggable material models, which may require material history arrays to determine the level of accumulated damage or the evolving yield stress in J2 plasticity models. For some applications laser rays are propagating through a virtual composite mesh consisting of the finest resolution representation of the modeled space. A new 2nd order accurate diffusion solver has been implemented for the thermal conduction and radiation transport packages. One application area is the modeling of laser/target effects including debris/shrapnel generation. Other application areas include warm dense matter, EUV lithography, and material wall interactions for fusion devices.
文摘IgA nephropathy(IgAN)is a leading cause of chronic kidney disease(CKD),which are commonly accompanied by dyslipidemia.Obesity is also associated with dyslipidemia and risk of CKD,but the relation of the dyslipidemia patterns with obesity and disease progression in IgAN patients remains unknown.Traditional Chinese medicine(TCM)and the combined treatment with corticosteroids and TCM have been shown to be of benefit for IgAN patients,but predictive markers for guiding these treatments are lacking.Here,we quantified 545 lipid species in the plasma from 196 participants,including 140 IgAN patients and 56 healthy volunteers,and revealed an altered plasma lipidome in IgAN patients as compared to healthy participants.Association analysis showed that a subgroup of glycerides,particularly triacylglycerols(TGs)containing docosahexaenoic acid,were positively associated with high body mass index(BMI)in under-or normal-weight IgAN patients,while several free fatty acids and sphingomyelins were positively associated with high BMI in overweight or obese IgAN patients.Further,our study suggested that elevated levels of eight lipids,mainly TG species containing linolenic acid,were independent risk factors for IgAN progression and also reported the prospective association of circulating lipids with treatment outcomes in IgAN.Taken together,our findings may not only help to achieve precision medicine but also provide a knowledge base for dietary intervention in the treatment of IgAN.