Glioblastoma(GBM)is a lethal cancer with limited therapeutic options.Dendritic cell(DC)-based cancer vaccines provide a promising approach for GBM treatment.Clinical studies suggest that other immunotherapeutic agents...Glioblastoma(GBM)is a lethal cancer with limited therapeutic options.Dendritic cell(DC)-based cancer vaccines provide a promising approach for GBM treatment.Clinical studies suggest that other immunotherapeutic agents may be combined with DC vaccines to further enhance antitumor activity.Here,we report a GBM case with combination immunotherapy consisting of DC vaccines,anti-programmed death-1(anti-PD-1)and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy,and the patient remained disease-free for 69 months.The patient received DC vaccines loaded with multiple forms of tumor antigens,including mRNA-tumor associated antigens(TAA),mRNA-neoantigens,and hypochlorous acid(HOCl)-oxidized tumor lysates.Furthermore,mRNA-TAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histocompatibility complex(MHC)class I and II antigen presentation.The treatment consisted of 42 DC cancer vaccine infusions,26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC infusions.The patient also received 28 doses of cyclophosphamide for depletion of regulatory T cells.No immunotherapy-related adverse events were observed during the treatment.Robust antitumor CD4t and CD8t T-cell responses were detected.The patient remains free of disease progression.This is the first case report on the combination of the above three agents to treat glioblastoma patients.Our results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient.A large-scale trial to validate these findings is warranted.展开更多
[Objectives] The aim was to study the contact activity of combination use of garlic,onion and stone calamus extracts on Helicoverpa armigera and their co-toxicity coefficient( CTC) and mixture ratio. [Methods] Leaf di...[Objectives] The aim was to study the contact activity of combination use of garlic,onion and stone calamus extracts on Helicoverpa armigera and their co-toxicity coefficient( CTC) and mixture ratio. [Methods] Leaf dipping method was used to study the contact activity of the three kinds of plant extracts against H. armigera. Based on this,the co-toxicity coefficient of the compound of the three kinds of extracts was determined. Orthogonal test was used to explore the optimal mixture ratio of the three kinds of extract for combination use. [Results]The extracts of garlic,onion and stone calamus had good inhibition and contract activity on H. armigera larvae. The LC50 values of the three kinds of plant extracts against H. armigera were 175. 0,217. 0 and 79. 2 mg/L,respectively. When the mixture ratios of stone calamus to garlic,and stone calamus to onion were both 2:1,the extract showed a synergistic effect( CTC > 120); when the mixture ratios of stone calamus to garlic,and stone calamus to onion were 1:1 and 1:2,respectively,the extracts showed an additive effect( 80 < CTC < 120); and then garlic extract and onion extract were mixed according to the ratio of 1:1,the additive effect was slight( CTC < 90). Among the three kinds of extracts,the extract of stone calamus showed the strongest contact activity,followed by that of garlic. The results of co-toxicity coefficient determination and orthogonal test showed that the contact activity of combination use of the three kinds of extracts was stronger than that of the single extract overall. When the extracts of garlic,onion and stone calamus were mixed according to the ratio of 2:3:1( mass concentration ratio),the contact activity of the compound against H. armigera reached 95. 3%. [Conclusions]The study results provide a scientific basis and theoretical reference for the development of new plant-derived pesticides based on the pharmacodynamics of garlic,onion and stone calamus.展开更多
High-power tunable femtosecond mid-infrared(MIR)pulses are of great interest for many scientific and industrial applications.Here we demonstrate a compact fluoride-fiber-based system that generates single solitons tun...High-power tunable femtosecond mid-infrared(MIR)pulses are of great interest for many scientific and industrial applications.Here we demonstrate a compact fluoride-fiber-based system that generates single solitons tunable from 3 to 3.8μm.The system is composed of an Er:ZBLAN fiber oscillator and amplifier followed by a fusion-spliced Dy:ZBLAN fiber amplifier.The Er:ZBLAN fiber amplifier acts as a power booster as well as a frequency shifter to generate Raman solitons up to 3μm.The Dy:ZBLAN fiber amplifier transfers the energy from the residual 2.8μm radiation into the Raman solitons using an in-band pumping scheme,and further extends the wavelength up to 3.8μm.Common residual pump radiation and secondary solitons accompanying the soliton self-frequency shift(SSFS)are recycled to amplify Raman solitons,consequently displaying a higher output power and pulse energy,a wider shifting range,and an excellent spectral purity.Stable 252 fs pulses at3.8μm with a record average power of 1.6 W and a pulse energy of 23 n J are generated.This work provides an effective way to develop high-power widely tunable ultrafast single-soliton MIR laser sources,and this method can facilitate the design of other SSFS-based laser systems for single-soliton generation.展开更多
The solid-liquid mixing is an important operation unit in the preparation of composites by stirring casting.High quality composite materials need good homogeneity and stable liquid level.In this work,the performances ...The solid-liquid mixing is an important operation unit in the preparation of composites by stirring casting.High quality composite materials need good homogeneity and stable liquid level.In this work,the performances of the Rotor-Stator agitator for solid suspension in stirred tank were investigated through CFD modeling,including the homogeneity,power consumption and liquid level stability.The Eulerian-Eulerian(E-E)multiphase model and the RNG k-εturbulence model were adopted for modeling the multiphase flow and the turbulence effects,respectively.The effect of various important parameters such as stirring speed,particle size,solid loading and the use of baffles were examined.Adding a stator structure with array holes outside the rotor can optimize the flow pattern,thereby improving the mixing uniformity and liquid level stability.The homogeneity and liquid level stability attained by the Rotor-Stator agitator were better than those for the A200(an axial-flow agitator)and the Rushton(a radial-flow agitator).展开更多
High-power femtosecond mid-infrared(MIR)lasers are of vast importance to both fundamental research and applications.We report a high-power femtosecond master oscillator power amplifier laser system consisting of a sin...High-power femtosecond mid-infrared(MIR)lasers are of vast importance to both fundamental research and applications.We report a high-power femtosecond master oscillator power amplifier laser system consisting of a singlemode Er:ZBLAN fiber mode-locked oscillator and pre-amplifier followed by a large-mode-area Er:ZBLAN fiber main amplifier.The main amplifier is actively cooled and bidirectionally pumped at 976 nm,generating a slope efficiency of 26.9%.Pulses of 8.12 W,148 fs at 2.8μm with a repetition rate of 69.65 MHz are achieved.To the best of our knowledge,this is the highest average power ever achieved from a femtosecond MIR laser source.Such a compact ultrafast laser system is promising for a wide range of applications,such as medical surgery and material processing.展开更多
The heat transfer perfonmance of a vertical two-phase closed thermosyphon(TPCT)used in a geothermal heat pump was experimentally investigated.The TPCT is a verticalplain steel pipe with inner diameter of 114 mm and bo...The heat transfer perfonmance of a vertical two-phase closed thermosyphon(TPCT)used in a geothermal heat pump was experimentally investigated.The TPCT is a verticalplain steel pipe with inner diameter of 114 mm and bored 368 m deep underground.Carbon dioxide(CO_(2))is used as working fluid.In the TPCT there is no condensation section.CO_(2)is condensed by the evaporator pf the heat pump,flows into the head of the TPCT and nuns down as a falling film along the inner wall of the pipe.For the heat transfer simulation in the TPCT,a quasi-dynamic model in which the mass transfer between the liquid and vapor phases as well as the conduction heat transfer from the surrounding soil towards the pipe is treated dynamically.However the film flow modeling is based on the Nusselt theory of frilm condenssation.The compauison of the experimental data with the numerical simulation is presented and discussed.展开更多
The coefficient of thermal expansion(CTE)mismatch between the reinforcement and the matrix results in thermal residual stresses and defects within metal-matrix composites(MMCs)upon cooling from the processing temperat...The coefficient of thermal expansion(CTE)mismatch between the reinforcement and the matrix results in thermal residual stresses and defects within metal-matrix composites(MMCs)upon cooling from the processing temperature to ambient temperature.The residual stresses and thermally induced defects play an important role in the mechanical properties of MMCs,it is critical to understand the mechanism of defect formation and evolution.This study provides atomistic simulations to reveal the generation of thermal residual stresses,dislocation and incomplete stacking fault tetrahedron(ISFT)during cooling in the idealized Cu/SiC composites.We found that dislocations are generated explosively in a certain temperature range during cooling,which results in a non-linear relationship between dislocation density and temperature.The combined effect of the stresses induced by CTE mismatch and the thermodynamic state of the metal leads to the rapid generation of dislocations.The Shockley partial and the highly stable stair rod are the two dominant dislocation structures.The immobile stair-rod dislocations and the highly stable ISFTs formed in the initial high temperature stage inhibit further development of plastic deformation.The present results provide new insights into the defect formation mechanism and the dislocation strengthening mechanism of MMCs caused by thermal mismatch between constituents.展开更多
We develop a novel network to segment water with significant appearance variation in videos.Unlike existing state-of-the-art video segmentation approaches that use a pre-trained feature recognition network and several...We develop a novel network to segment water with significant appearance variation in videos.Unlike existing state-of-the-art video segmentation approaches that use a pre-trained feature recognition network and several previous frames to guide segmentation,we accommodate the object’s appearance variation by considering features observed from the current frame.When dealing with segmentation of objects such as water,whose appearance is non-uniform and changing dynamically,our pipeline can produce more reliable and accurate segmentation results than existing algorithms.展开更多
基金supported by Natural Science Foundation of Shaanxi Province(Grant No.:2019ZY-CXPT-03-01)to Ping Zhu and Key Research and Development Program of Shaanxi Province(Grant No.:2020ZDLSF03-02)to Zhi-Nan Chen and Huijie Bian as well as Tricision Biotherapeutics Inc.
文摘Glioblastoma(GBM)is a lethal cancer with limited therapeutic options.Dendritic cell(DC)-based cancer vaccines provide a promising approach for GBM treatment.Clinical studies suggest that other immunotherapeutic agents may be combined with DC vaccines to further enhance antitumor activity.Here,we report a GBM case with combination immunotherapy consisting of DC vaccines,anti-programmed death-1(anti-PD-1)and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy,and the patient remained disease-free for 69 months.The patient received DC vaccines loaded with multiple forms of tumor antigens,including mRNA-tumor associated antigens(TAA),mRNA-neoantigens,and hypochlorous acid(HOCl)-oxidized tumor lysates.Furthermore,mRNA-TAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histocompatibility complex(MHC)class I and II antigen presentation.The treatment consisted of 42 DC cancer vaccine infusions,26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC infusions.The patient also received 28 doses of cyclophosphamide for depletion of regulatory T cells.No immunotherapy-related adverse events were observed during the treatment.Robust antitumor CD4t and CD8t T-cell responses were detected.The patient remains free of disease progression.This is the first case report on the combination of the above three agents to treat glioblastoma patients.Our results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient.A large-scale trial to validate these findings is warranted.
文摘[Objectives] The aim was to study the contact activity of combination use of garlic,onion and stone calamus extracts on Helicoverpa armigera and their co-toxicity coefficient( CTC) and mixture ratio. [Methods] Leaf dipping method was used to study the contact activity of the three kinds of plant extracts against H. armigera. Based on this,the co-toxicity coefficient of the compound of the three kinds of extracts was determined. Orthogonal test was used to explore the optimal mixture ratio of the three kinds of extract for combination use. [Results]The extracts of garlic,onion and stone calamus had good inhibition and contract activity on H. armigera larvae. The LC50 values of the three kinds of plant extracts against H. armigera were 175. 0,217. 0 and 79. 2 mg/L,respectively. When the mixture ratios of stone calamus to garlic,and stone calamus to onion were both 2:1,the extract showed a synergistic effect( CTC > 120); when the mixture ratios of stone calamus to garlic,and stone calamus to onion were 1:1 and 1:2,respectively,the extracts showed an additive effect( 80 < CTC < 120); and then garlic extract and onion extract were mixed according to the ratio of 1:1,the additive effect was slight( CTC < 90). Among the three kinds of extracts,the extract of stone calamus showed the strongest contact activity,followed by that of garlic. The results of co-toxicity coefficient determination and orthogonal test showed that the contact activity of combination use of the three kinds of extracts was stronger than that of the single extract overall. When the extracts of garlic,onion and stone calamus were mixed according to the ratio of 2:3:1( mass concentration ratio),the contact activity of the compound against H. armigera reached 95. 3%. [Conclusions]The study results provide a scientific basis and theoretical reference for the development of new plant-derived pesticides based on the pharmacodynamics of garlic,onion and stone calamus.
基金National Natural Science Foundation of China(61775146,61905151,61935014,61975136,62105222)Basic and Applied Basic Research Foundation of Guangdong Province(2019A1515010699)+1 种基金Natural Science Basic Research Program of Shaanxi(2020JQ-204)Shenzhen Science and Technology Program(CJGJZD20200617103003009,JCYJ20210324094400001)。
文摘High-power tunable femtosecond mid-infrared(MIR)pulses are of great interest for many scientific and industrial applications.Here we demonstrate a compact fluoride-fiber-based system that generates single solitons tunable from 3 to 3.8μm.The system is composed of an Er:ZBLAN fiber oscillator and amplifier followed by a fusion-spliced Dy:ZBLAN fiber amplifier.The Er:ZBLAN fiber amplifier acts as a power booster as well as a frequency shifter to generate Raman solitons up to 3μm.The Dy:ZBLAN fiber amplifier transfers the energy from the residual 2.8μm radiation into the Raman solitons using an in-band pumping scheme,and further extends the wavelength up to 3.8μm.Common residual pump radiation and secondary solitons accompanying the soliton self-frequency shift(SSFS)are recycled to amplify Raman solitons,consequently displaying a higher output power and pulse energy,a wider shifting range,and an excellent spectral purity.Stable 252 fs pulses at3.8μm with a record average power of 1.6 W and a pulse energy of 23 n J are generated.This work provides an effective way to develop high-power widely tunable ultrafast single-soliton MIR laser sources,and this method can facilitate the design of other SSFS-based laser systems for single-soliton generation.
基金financially supported by the National Natural Science Foundation of China(No.52006041)the Guangdong Academy of Sciences(Nos.2021GDASYL-20210103101,2020GDASYL-20200101001,2022GDASZH-2022010109)the Guangdong Major Project of Basic and Applied Basic Research(No.2020B0301030006)。
文摘The solid-liquid mixing is an important operation unit in the preparation of composites by stirring casting.High quality composite materials need good homogeneity and stable liquid level.In this work,the performances of the Rotor-Stator agitator for solid suspension in stirred tank were investigated through CFD modeling,including the homogeneity,power consumption and liquid level stability.The Eulerian-Eulerian(E-E)multiphase model and the RNG k-εturbulence model were adopted for modeling the multiphase flow and the turbulence effects,respectively.The effect of various important parameters such as stirring speed,particle size,solid loading and the use of baffles were examined.Adding a stator structure with array holes outside the rotor can optimize the flow pattern,thereby improving the mixing uniformity and liquid level stability.The homogeneity and liquid level stability attained by the Rotor-Stator agitator were better than those for the A200(an axial-flow agitator)and the Rushton(a radial-flow agitator).
基金the National Natural Science Foundation of China(61975136,61935014,62105222,61775146,61905151)the Basic and Applied Basic Research Foundation of Guangdong Province(2019A1515010699)+1 种基金the Shenzhen Science and Technology Innovation Program(CJGJZD20200617103003009,JCYJ20210324094400001,GJHZ20210705141801006)the Beijing Natural Science Foundation(JQ21019).
文摘High-power femtosecond mid-infrared(MIR)lasers are of vast importance to both fundamental research and applications.We report a high-power femtosecond master oscillator power amplifier laser system consisting of a singlemode Er:ZBLAN fiber mode-locked oscillator and pre-amplifier followed by a large-mode-area Er:ZBLAN fiber main amplifier.The main amplifier is actively cooled and bidirectionally pumped at 976 nm,generating a slope efficiency of 26.9%.Pulses of 8.12 W,148 fs at 2.8μm with a repetition rate of 69.65 MHz are achieved.To the best of our knowledge,this is the highest average power ever achieved from a femtosecond MIR laser source.Such a compact ultrafast laser system is promising for a wide range of applications,such as medical surgery and material processing.
基金The present research work was supported by the Federal Ministry for Economic Affairs and Energy of Germanyunder the funding code FKZ:03ET1050B.
文摘The heat transfer perfonmance of a vertical two-phase closed thermosyphon(TPCT)used in a geothermal heat pump was experimentally investigated.The TPCT is a verticalplain steel pipe with inner diameter of 114 mm and bored 368 m deep underground.Carbon dioxide(CO_(2))is used as working fluid.In the TPCT there is no condensation section.CO_(2)is condensed by the evaporator pf the heat pump,flows into the head of the TPCT and nuns down as a falling film along the inner wall of the pipe.For the heat transfer simulation in the TPCT,a quasi-dynamic model in which the mass transfer between the liquid and vapor phases as well as the conduction heat transfer from the surrounding soil towards the pipe is treated dynamically.However the film flow modeling is based on the Nusselt theory of frilm condenssation.The compauison of the experimental data with the numerical simulation is presented and discussed.
基金supported by Guangdong Academy of Sciences(Nos.2021GDASYL-20210103102,2021GDASYL-20210103099)Guangdong Province Key Area R&D Program(No.2019B010940001)+1 种基金Guangzhou Science and Technology Project(No.202102020844)National Natural Science Foundation of China(No.12072110)。
文摘The coefficient of thermal expansion(CTE)mismatch between the reinforcement and the matrix results in thermal residual stresses and defects within metal-matrix composites(MMCs)upon cooling from the processing temperature to ambient temperature.The residual stresses and thermally induced defects play an important role in the mechanical properties of MMCs,it is critical to understand the mechanism of defect formation and evolution.This study provides atomistic simulations to reveal the generation of thermal residual stresses,dislocation and incomplete stacking fault tetrahedron(ISFT)during cooling in the idealized Cu/SiC composites.We found that dislocations are generated explosively in a certain temperature range during cooling,which results in a non-linear relationship between dislocation density and temperature.The combined effect of the stresses induced by CTE mismatch and the thermodynamic state of the metal leads to the rapid generation of dislocations.The Shockley partial and the highly stable stair rod are the two dominant dislocation structures.The immobile stair-rod dislocations and the highly stable ISFTs formed in the initial high temperature stage inhibit further development of plastic deformation.The present results provide new insights into the defect formation mechanism and the dislocation strengthening mechanism of MMCs caused by thermal mismatch between constituents.
基金supported in part by the National Science Foundation under Grant EAR 1760582the Louisiana Board of Regents ITRS LEQSF(2018-21)-RD-B-03.
文摘We develop a novel network to segment water with significant appearance variation in videos.Unlike existing state-of-the-art video segmentation approaches that use a pre-trained feature recognition network and several previous frames to guide segmentation,we accommodate the object’s appearance variation by considering features observed from the current frame.When dealing with segmentation of objects such as water,whose appearance is non-uniform and changing dynamically,our pipeline can produce more reliable and accurate segmentation results than existing algorithms.
