Seismic migration and inversion are closely related techniques to portray subsurface images and identify hydrocarbon reservoirs.Seismic migration aims at obtaining structural images of subsurface geologic discontinuit...Seismic migration and inversion are closely related techniques to portray subsurface images and identify hydrocarbon reservoirs.Seismic migration aims at obtaining structural images of subsurface geologic discontinuities.More specifically,seismic migration estimates the reflectivity function(stacked average reflectivity or pre-stack angle-dependent reflectivity)from seismic reflection data.On the other hand,seismic inversion quantitatively estimates the intrinsic rock properties of subsurface formulations.Such seismic inversion methods are applicable to detect hydrocarbon reservoirs that may exhibit lateral variations in the inverted parameters.Although there exist many differences,pre-stack seismic migration is similar with the first iteration of the general linearized seismic inversion.Usually,seismic migration and inversion techniques assume an acoustic or isotropic elastic medium.Unconventional reservoirs such as shale and tight sand formation have notable anisotropic property.We present a linearized waveform inversion(LWI)scheme for weakly anisotropic elastic media with vertical transversely isotropic(VTI)symmetry.It is based on two-way anisotropic elastic wave equation and simultaneously inverts for the localized perturbations(ΔVp_(0)/Vp_(0)/Vs_(0)/Vs_(0)/,Δ∈,Δδ)from the long-wavelength reference model.Our proposed VTI-elastic LWI is an iterative method that requires a forward and an adjoint operator acting on vectors in each iteration.We derive the forward Born approximation operator by perturbation theory and adjoint operator via adjoint-state method.The inversion has improved the quality of the images and reduces the multi-parameter crosstalk comparing with the adjoint-based images.We have observed that the multi-parameter crosstalk problem is more prominent in the inversion images for Thomsen anisotropy parameters.Especially,the Thomsen parameter is the most difficult to resolve.We also analyze the multi-parameter crosstalk using scattering radiation patterns.The linearized waveform inversion for VTI-elastic media presented in this article provides quantitative information of the rock properties that has the potential to help identify hydrocarbon reservoirs.展开更多
Common-image gathers are extensively used in amplitude versus angle(AVA)and migration velocity analysis(MVA).The current state of methods for anisotropic angle gathers extraction use slant-stack,local Fourier transfor...Common-image gathers are extensively used in amplitude versus angle(AVA)and migration velocity analysis(MVA).The current state of methods for anisotropic angle gathers extraction use slant-stack,local Fourier transform or low-rank approximation,which requires much computation.Based on an anisotropic-Helmholtz P/S wave-mode decomposition method,we propose a novel and efficient approach to produce angle-domain common-image gathers(ADCIGs)in the elastic reverse time migration(ERTM)of VTI media.To start with,we derive an anisotropic-Helmholtz decomposition operator from the Christoffel equation in VTI media,and use this operator to derive the decomposed formulations for anisotropic P/S waves.Second,we employ the first-order Taylor expansion to calculate the normalized term of decomposed formulations and obtain the anisotropic-Helmholtz decomposition method,which generates the separated P/S wavefields with correct amplitudes and phases.Third,we develop a novel way that uses the anisotropic-Helmholtz decomposition operator to define the polari-zation angles for anisotropic P/S waves and substitute these angles to decomposing formulations.The polarization angles are then calculated directly from the separated vector P-and S-wavefields and converted to the phase angles.The ADCIGs are thusly produced by applying the phase angles to VTI ERTM.In addition,we develop a concise approximate expression of residual moveout(RMO)for PP-reflections of flat reflectors in VTI media,which avoids the complex transformations between the group angles and the phase angles.The approximate RMO curves show a good agreement with the exact solution and can be used as a tool to assess the migration velocity errors.As demonstrated by two selected examples,our ADCIGs not only produce the correct kinematic responses with regards to different velocity pertubatation,but also generate the reliable amplitude responses versus different angle.The final stacking images of ADCIGs data exhibit the identical imaging effect as that of VTI ERTM.展开更多
Background: Irreversible electroporation(IRE) is a novel ablative technique for hepatobiliary and pancreatic cancers. This review summarizes the data regarding the safety and efficacy of IRE in the treatment of hepato...Background: Irreversible electroporation(IRE) is a novel ablative technique for hepatobiliary and pancreatic cancers. This review summarizes the data regarding the safety and efficacy of IRE in the treatment of hepatobiliary and pancreatic cancers. Data sources: Studies were identified by searching Pub Med and Embase for articles published in English from database inception through July 31, 2017. For inclusion, each clinical study had to report morbidity and survival data on hepatobiliary and pancreatic cancers treated with IRE and contain at least 10 patients. Studies that met these criteria were included for analysis. Two authors assessed each clinical study for data extraction. The controversial parts were resolved through discussion with seniors. Results: A total of 24 clinical studies were included. Fourteen focused on hepatic ablation with IRE comprising 437 patients with 666 lesions of different tumor types. Two patients(0.5%) died after the IRE procedure. Morbidity of hepatic ablation with IRE ranged from 7% to 35%. Most complications were mild. Complete response for hepatic tumors was reported as 57%–97%. Ten studies with 455 patients focused on pancreatic IRE. The overall mortality of IRE in pancreatic cancer was 2%. Overall severe morbidity of IRE in pancreatic cancer ranged from 0 to 20%. The median overall survival after IRE ranged from 7 to 23 months. Patients treated with IRE combined with surgical resection showed a longer overall survival. Conclusions: IRE significantly improves the prognosis of advanced hepatobiliary and pancreatic malignances, and companied with less complications. Hence, IRE is a relatively safe and effective non-thermal ablation strategy and potentially recommended as an option for therapy of patients with hepatobiliary and pancreatic malignances.展开更多
A Levenberg–Marquardt Gaussian fitting algorithm has been used for analyzing the overlap of three peaks(the 583-ke V peak of^(208)Tl, the 609-ke V peak of214 Bi, and the 662-ke V peak of^(137)Cs) using an in situ Na ...A Levenberg–Marquardt Gaussian fitting algorithm has been used for analyzing the overlap of three peaks(the 583-ke V peak of^(208)Tl, the 609-ke V peak of214 Bi, and the 662-ke V peak of^(137)Cs) using an in situ Na I(Tl) scintillation spectrometer. The algorithm, in addition,was compared with a genetic algorithm used for multiple deconvolution. The three fitted peak areas(583, 609, and662 ke V) were calculated from the measured gamma-ray spectra obtained from a simulation experiment in which a^(137) Cs source was buried at different soil depths(from 18 to38 cm). The application of the Levenberg–Marquardt algorithm yielded similar results compared to the genetic algorithm. A lack-of-fit test showed that the fitting is good when the instrumental noise levels were estimated from replicated analyses. The relative fitting error of the total net area and the residual standard deviation were within 5 %and 0.04, respectively, and the goodness of the fitting was better than 0.98. While the methods used in this paper give high performance, the results may lead to incorrect estimation when the signal-to-noise ratio is smaller than-30 d B. This study is useful for the determination of radioactive specific activity of^(137) Cs by in situ spectrometry.展开更多
Hierarchically porous carbons(HPCs)with multimodal pores have attracted considerable attention due to their unique physical and chemical properties and various application potentials in heterogeneous catalysis,environ...Hierarchically porous carbons(HPCs)with multimodal pores have attracted considerable attention due to their unique physical and chemical properties and various application potentials in heterogeneous catalysis,environmental treatment,and energy storage and conversion.Herein,we report a general and simple zinc salts-assisted method for the synthesis of HPCs with varied porosity and chemical func-tionalities by the direct carbonization of diverse biomass and wastes.During the carbonization,zinc salts are thermally decomposed into nanoparticles that serve as in-situ templates to introduce nanopores in carbons.The prepared HPCs exhibit high specific surface areas(up to 2432 m2 g-1),large pore volumes(up to 4.30 cm^(3)g^(-1)),and broad pore size distributions.Moreover,the zinc salts can be recovered and recycled,supporting the sustainable production of HPCs on large scale.The prepared HPCs-supported catalysts with atomically dispersed metal sites exhibit promising electrocatalytic performance for the oxygen reduction reaction.展开更多
Replacing traditional polymer-based precursors with small molecules is a promising pathway toward facile and controllable preparation of porous carbons but remains a prohibitive challenge because of the high volatilit...Replacing traditional polymer-based precursors with small molecules is a promising pathway toward facile and controllable preparation of porous carbons but remains a prohibitive challenge because of the high volatility of small molecules.Herein,a simple,general,and controllable method is reported to prepare porous carbons by converting small organic molecules into organic molecular salts followed by pyrolysis.The robust electrostatic force holding organic molecular salts together leads to negligible volatility and thus ensures the formation of carbons under high-temperature pyrolysis.Meanwhile,metal moieties in organic molecular salts can be evolved into in-situ templates or activators during pyrolysis to create nanopores.The modular nature of organic molecular salts allows easy control of the porosity and chemical doping of carbons at a molecular level.The sulfur-doped carbon prepared by the ionic solid strategy can serve as robust support to prepare small-sized intermetallic PtCo catalysts,which exhibit a high mass activity of 1.62 A·mgPt^(−1)in catalyzing oxygen reduction reaction for fuel cell applications.展开更多
The mammalian target of rapamycin(m TOR) pathway is abnormally activated in lung cancer.However, the anti-lung cancer effect of m TOR inhibitors as monotherapy is modest. Here, we identified that ginsenoside Rh2, an a...The mammalian target of rapamycin(m TOR) pathway is abnormally activated in lung cancer.However, the anti-lung cancer effect of m TOR inhibitors as monotherapy is modest. Here, we identified that ginsenoside Rh2, an active component of Panax ginseng C. A. Mey., enhanced the anti-cancer effect of the m TOR inhibitor everolimus both in vitro and in vivo. Moreover, ginsenoside Rh2 alleviated the hepatic fat accumulation caused by everolimus in xenograft nude mice models. The combination of everolimus and ginsenoside Rh2(labeled Eve-Rh2) induced caspase-independent cell death and cytoplasmic vacuolation in lung cancer cells, indicating that Eve-Rh2 prevented tumor progression by triggering paraptosis. EveRh2 up-regulated the expression of c-MYC in cancer cells as well as tumor tissues. The increased cMYC mediated the accumulation of tribbles homolog 3(TRIB3)/P62+ aggresomes and consequently triggered paraptosis, bypassing the classical c-MYC/MAX pathway. Our study offers a potential effective and safe strategy for the treatment of lung cancer. Moreover, we have identified a new mechanism of TRIB3/P62+ aggresomes-triggered paraptosis and revealed a unique function of c-MYC.展开更多
Steroid medication is used extensively in clinical applications and comprises a large and vital part of the pharmaceutical industry. However, the difficulty of separating 4-androstene-3,17-dione (AD) from 1,4-andros...Steroid medication is used extensively in clinical applications and comprises a large and vital part of the pharmaceutical industry. However, the difficulty of separating 4-androstene-3,17-dione (AD) from 1,4-androstadiene- 3,17-dione (ADD) restricts the application of the microbial transformation of phytosterols in the industry. A novel at- mospheric and room temperature plasma (ARTP) treatment, which employs helium as the working gas, was used to generate Mycobacterium neoaurum mutants producing large amounts of AD. After treatment of cultures with ARTP, four mutants were selected using a novel screening method with a color assay. Among the mutants, M. neoaurum ZADF-4 was considered the best candidate for industrial application. When the fermentation medium contained 15 g/L phytosterols and was cultivated on a rotary shaker at 160 r/min at 30 ~C for 7 d, (6.28+0.11) g/L of AD and (0.82+0.05) g/L of ADD were produced by the ZADF-4 mutant, compared with (4.83+0.13) g/L of AD and (2.34+0.06) g/L of ADD by the original strain, Iv~. neoaururn ZAD. Compared with ZAD, the molar yield of AD increased from 48.3% to 60.3% in the ZADF-4 mutant. This result indicates that ZADF-4 may have potential for industrial production of AD.展开更多
文摘Seismic migration and inversion are closely related techniques to portray subsurface images and identify hydrocarbon reservoirs.Seismic migration aims at obtaining structural images of subsurface geologic discontinuities.More specifically,seismic migration estimates the reflectivity function(stacked average reflectivity or pre-stack angle-dependent reflectivity)from seismic reflection data.On the other hand,seismic inversion quantitatively estimates the intrinsic rock properties of subsurface formulations.Such seismic inversion methods are applicable to detect hydrocarbon reservoirs that may exhibit lateral variations in the inverted parameters.Although there exist many differences,pre-stack seismic migration is similar with the first iteration of the general linearized seismic inversion.Usually,seismic migration and inversion techniques assume an acoustic or isotropic elastic medium.Unconventional reservoirs such as shale and tight sand formation have notable anisotropic property.We present a linearized waveform inversion(LWI)scheme for weakly anisotropic elastic media with vertical transversely isotropic(VTI)symmetry.It is based on two-way anisotropic elastic wave equation and simultaneously inverts for the localized perturbations(ΔVp_(0)/Vp_(0)/Vs_(0)/Vs_(0)/,Δ∈,Δδ)from the long-wavelength reference model.Our proposed VTI-elastic LWI is an iterative method that requires a forward and an adjoint operator acting on vectors in each iteration.We derive the forward Born approximation operator by perturbation theory and adjoint operator via adjoint-state method.The inversion has improved the quality of the images and reduces the multi-parameter crosstalk comparing with the adjoint-based images.We have observed that the multi-parameter crosstalk problem is more prominent in the inversion images for Thomsen anisotropy parameters.Especially,the Thomsen parameter is the most difficult to resolve.We also analyze the multi-parameter crosstalk using scattering radiation patterns.The linearized waveform inversion for VTI-elastic media presented in this article provides quantitative information of the rock properties that has the potential to help identify hydrocarbon reservoirs.
基金supported by the National Key R&D Program of China(2020YFA0710604 and 2017YFC1500303)the Science Foundation of the China University of Petroleum,Beijing(2462019YJRC007 and 2462020YXZZ047)the Strategic Cooperation Technology Projects of CNPC and CUPB(ZLZX2020-05).
文摘Common-image gathers are extensively used in amplitude versus angle(AVA)and migration velocity analysis(MVA).The current state of methods for anisotropic angle gathers extraction use slant-stack,local Fourier transform or low-rank approximation,which requires much computation.Based on an anisotropic-Helmholtz P/S wave-mode decomposition method,we propose a novel and efficient approach to produce angle-domain common-image gathers(ADCIGs)in the elastic reverse time migration(ERTM)of VTI media.To start with,we derive an anisotropic-Helmholtz decomposition operator from the Christoffel equation in VTI media,and use this operator to derive the decomposed formulations for anisotropic P/S waves.Second,we employ the first-order Taylor expansion to calculate the normalized term of decomposed formulations and obtain the anisotropic-Helmholtz decomposition method,which generates the separated P/S wavefields with correct amplitudes and phases.Third,we develop a novel way that uses the anisotropic-Helmholtz decomposition operator to define the polari-zation angles for anisotropic P/S waves and substitute these angles to decomposing formulations.The polarization angles are then calculated directly from the separated vector P-and S-wavefields and converted to the phase angles.The ADCIGs are thusly produced by applying the phase angles to VTI ERTM.In addition,we develop a concise approximate expression of residual moveout(RMO)for PP-reflections of flat reflectors in VTI media,which avoids the complex transformations between the group angles and the phase angles.The approximate RMO curves show a good agreement with the exact solution and can be used as a tool to assess the migration velocity errors.As demonstrated by two selected examples,our ADCIGs not only produce the correct kinematic responses with regards to different velocity pertubatation,but also generate the reliable amplitude responses versus different angle.The final stacking images of ADCIGs data exhibit the identical imaging effect as that of VTI ERTM.
基金supported by grants from the Traditional Chinese Medicine Scientific Research Fund Project of Zhejiang province(No.2017ZA079)the Key Research Development Program of Zhejiang province(No.2018C03018)+1 种基金the Key Science and Tech-nology Program of Zhejiang Provience(No.WKJ-ZJ-1923)the National S&T Major Project of China(No.2018ZX10301201)
文摘Background: Irreversible electroporation(IRE) is a novel ablative technique for hepatobiliary and pancreatic cancers. This review summarizes the data regarding the safety and efficacy of IRE in the treatment of hepatobiliary and pancreatic cancers. Data sources: Studies were identified by searching Pub Med and Embase for articles published in English from database inception through July 31, 2017. For inclusion, each clinical study had to report morbidity and survival data on hepatobiliary and pancreatic cancers treated with IRE and contain at least 10 patients. Studies that met these criteria were included for analysis. Two authors assessed each clinical study for data extraction. The controversial parts were resolved through discussion with seniors. Results: A total of 24 clinical studies were included. Fourteen focused on hepatic ablation with IRE comprising 437 patients with 666 lesions of different tumor types. Two patients(0.5%) died after the IRE procedure. Morbidity of hepatic ablation with IRE ranged from 7% to 35%. Most complications were mild. Complete response for hepatic tumors was reported as 57%–97%. Ten studies with 455 patients focused on pancreatic IRE. The overall mortality of IRE in pancreatic cancer was 2%. Overall severe morbidity of IRE in pancreatic cancer ranged from 0 to 20%. The median overall survival after IRE ranged from 7 to 23 months. Patients treated with IRE combined with surgical resection showed a longer overall survival. Conclusions: IRE significantly improves the prognosis of advanced hepatobiliary and pancreatic malignances, and companied with less complications. Hence, IRE is a relatively safe and effective non-thermal ablation strategy and potentially recommended as an option for therapy of patients with hepatobiliary and pancreatic malignances.
基金supported by the National Natural Science Foundation of China(No.41474107)
文摘A Levenberg–Marquardt Gaussian fitting algorithm has been used for analyzing the overlap of three peaks(the 583-ke V peak of^(208)Tl, the 609-ke V peak of214 Bi, and the 662-ke V peak of^(137)Cs) using an in situ Na I(Tl) scintillation spectrometer. The algorithm, in addition,was compared with a genetic algorithm used for multiple deconvolution. The three fitted peak areas(583, 609, and662 ke V) were calculated from the measured gamma-ray spectra obtained from a simulation experiment in which a^(137) Cs source was buried at different soil depths(from 18 to38 cm). The application of the Levenberg–Marquardt algorithm yielded similar results compared to the genetic algorithm. A lack-of-fit test showed that the fitting is good when the instrumental noise levels were estimated from replicated analyses. The relative fitting error of the total net area and the residual standard deviation were within 5 %and 0.04, respectively, and the goodness of the fitting was better than 0.98. While the methods used in this paper give high performance, the results may lead to incorrect estimation when the signal-to-noise ratio is smaller than-30 d B. This study is useful for the determination of radioactive specific activity of^(137) Cs by in situ spectrometry.
基金the funding support from the National Key Research and Development Program of China(grant No.2018YFA0702001)the National Natural Science Foundation of China(grant Nos.22071225 and 22221003)+4 种基金the Plan for Anhui Major Provincial Science&Technology Project(grant Nos.202203a0520013 and 202103a05020015)the Fundamental Research Funds for the Central Universities(grant No WK2060190103)the Joint Funds from Hefei National Synchrotron Radiation Laboratory(grant No.KY2060000175)Collaborative Innovation Program of Hefei Science Center of CAS(grant No.2021HSC-CIP015)USTC Research Funds of the Double First-Class Initiative.
文摘Hierarchically porous carbons(HPCs)with multimodal pores have attracted considerable attention due to their unique physical and chemical properties and various application potentials in heterogeneous catalysis,environmental treatment,and energy storage and conversion.Herein,we report a general and simple zinc salts-assisted method for the synthesis of HPCs with varied porosity and chemical func-tionalities by the direct carbonization of diverse biomass and wastes.During the carbonization,zinc salts are thermally decomposed into nanoparticles that serve as in-situ templates to introduce nanopores in carbons.The prepared HPCs exhibit high specific surface areas(up to 2432 m2 g-1),large pore volumes(up to 4.30 cm^(3)g^(-1)),and broad pore size distributions.Moreover,the zinc salts can be recovered and recycled,supporting the sustainable production of HPCs on large scale.The prepared HPCs-supported catalysts with atomically dispersed metal sites exhibit promising electrocatalytic performance for the oxygen reduction reaction.
基金We acknowledge the funding support from the National Key Research and Development Program of China(No.2018YFA0702001)the National Natural Science Foundation of China(No.22071225)+6 种基金the Fundamental Research Funds for the Central Universities(No.WK2060190103)the Joint Funds from Hefei National Synchrotron Radiation Laboratory(No.KY2060000175)the Natural Science Foundation of Guangdong Province(No.2021A1515012356)the Research Grant for Scientific Platform and Project of Guangdong Provincial Education office(No.2019KTSCX151)Shenzhen Government’s Plan of Science and Technology(No.JCYJ20180305125247308)the Collaborative Innovation Program of Hefei Science Center of CAS(No.2021HSC-CIP015)L.D.F.acknowledges the support from the Instrumental Analysis Center of Shenzhen University(Xili Campus).
文摘Replacing traditional polymer-based precursors with small molecules is a promising pathway toward facile and controllable preparation of porous carbons but remains a prohibitive challenge because of the high volatility of small molecules.Herein,a simple,general,and controllable method is reported to prepare porous carbons by converting small organic molecules into organic molecular salts followed by pyrolysis.The robust electrostatic force holding organic molecular salts together leads to negligible volatility and thus ensures the formation of carbons under high-temperature pyrolysis.Meanwhile,metal moieties in organic molecular salts can be evolved into in-situ templates or activators during pyrolysis to create nanopores.The modular nature of organic molecular salts allows easy control of the porosity and chemical doping of carbons at a molecular level.The sulfur-doped carbon prepared by the ionic solid strategy can serve as robust support to prepare small-sized intermetallic PtCo catalysts,which exhibit a high mass activity of 1.62 A·mgPt^(−1)in catalyzing oxygen reduction reaction for fuel cell applications.
基金supported by the National Natural Science Foundation of China(No.81973516)partially supported by the Science and Technology Development Fund,Macao S.A.R,China(Nos.024/2016/A1 and 0129/2019/A3)University of Macao(No.CPG2021-00022-ICMS)。
文摘The mammalian target of rapamycin(m TOR) pathway is abnormally activated in lung cancer.However, the anti-lung cancer effect of m TOR inhibitors as monotherapy is modest. Here, we identified that ginsenoside Rh2, an active component of Panax ginseng C. A. Mey., enhanced the anti-cancer effect of the m TOR inhibitor everolimus both in vitro and in vivo. Moreover, ginsenoside Rh2 alleviated the hepatic fat accumulation caused by everolimus in xenograft nude mice models. The combination of everolimus and ginsenoside Rh2(labeled Eve-Rh2) induced caspase-independent cell death and cytoplasmic vacuolation in lung cancer cells, indicating that Eve-Rh2 prevented tumor progression by triggering paraptosis. EveRh2 up-regulated the expression of c-MYC in cancer cells as well as tumor tissues. The increased cMYC mediated the accumulation of tribbles homolog 3(TRIB3)/P62+ aggresomes and consequently triggered paraptosis, bypassing the classical c-MYC/MAX pathway. Our study offers a potential effective and safe strategy for the treatment of lung cancer. Moreover, we have identified a new mechanism of TRIB3/P62+ aggresomes-triggered paraptosis and revealed a unique function of c-MYC.
基金supported by the National Basic Research Program(973)of China(No.2012CB725202)the National High-Tech R&D Program(863)of China(No.2011AA02A211)+4 种基金the National Natural Science Foundation of China(No.21276110)the Fundamental Research Funds for the Central Universities(Nos.JUSRP51306A and JUSRP11545)the National 111 Project of China’s Higher Education(No.111-2-06)the Program of the Key Laboratory of Industrial Biotechnology,Ministry of Education,China(No.KLIB-KF201406)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD),China
文摘Steroid medication is used extensively in clinical applications and comprises a large and vital part of the pharmaceutical industry. However, the difficulty of separating 4-androstene-3,17-dione (AD) from 1,4-androstadiene- 3,17-dione (ADD) restricts the application of the microbial transformation of phytosterols in the industry. A novel at- mospheric and room temperature plasma (ARTP) treatment, which employs helium as the working gas, was used to generate Mycobacterium neoaurum mutants producing large amounts of AD. After treatment of cultures with ARTP, four mutants were selected using a novel screening method with a color assay. Among the mutants, M. neoaurum ZADF-4 was considered the best candidate for industrial application. When the fermentation medium contained 15 g/L phytosterols and was cultivated on a rotary shaker at 160 r/min at 30 ~C for 7 d, (6.28+0.11) g/L of AD and (0.82+0.05) g/L of ADD were produced by the ZADF-4 mutant, compared with (4.83+0.13) g/L of AD and (2.34+0.06) g/L of ADD by the original strain, Iv~. neoaururn ZAD. Compared with ZAD, the molar yield of AD increased from 48.3% to 60.3% in the ZADF-4 mutant. This result indicates that ZADF-4 may have potential for industrial production of AD.