Metabolic flexibility has emerged as a critical determinant of CD8+T-cell antitumor activity,yet the mechanisms driving the metabolic flexibility of T cells have not been determined.In this study,we investigated the i...Metabolic flexibility has emerged as a critical determinant of CD8+T-cell antitumor activity,yet the mechanisms driving the metabolic flexibility of T cells have not been determined.In this study,we investigated the influence of the nuclear cap-binding complex(CBC)adaptor protein ARS2 on mature T cells.In doing so,we discovered a novel signaling axis that endows activated CD8+T cells with flexibility of glucose catabolism.ARS2 upregulation driven by CD28 signaling reinforced splicing factor recruitment to pre-mRNAs and affected approximately one-third of T-cell activation-induced alternative splicing events.Among these effects,the CD28-ARS2 axis suppressed the expression of the M1 isoform of pyruvate kinase in favor of PKM2,a key determinant of CD8+T-cell glucose utilization,interferon gamma production,and antitumor effector function.Importantly,PKM alternative splicing occurred independently of CD28-driven PI3K pathway activation,revealing a novel means by which costimulation reprograms glucose metabolism in CD8+T cells.展开更多
In this work,the effects of the frequency,pressure,gas composition,and secondary-electron emission coefficient on the discharge mode in capacitively coupled Ar/O_(2) plasmas were carefully studied through simulations....In this work,the effects of the frequency,pressure,gas composition,and secondary-electron emission coefficient on the discharge mode in capacitively coupled Ar/O_(2) plasmas were carefully studied through simulations.Three discharge modes,i.e.,α,γ,and drift-ambipolar(DA),were considered in this study.The results show that a mode transition from theγ-DA hybrid mode dominated by theγmode to the DA-αhybrid mode dominated by the DA mode is induced by increasing the frequency from 100 k Hz to 40 MHz.Furthermore,the electron temperature decreases with increasing frequency,while the plasma density first decreases and then increases.It was found that the electronegativity increases slightly with increasing pressure in the lowfrequency region,and it increases notably with increasing pressure in the high-frequency region.It was also observed that the frequency corresponding to the mode transition fromγto DA decreased when the secondary-electron emission coefficient was decreased.Finally,it was found that increasing the oxygen content weakens theγmode and enhances the DA mode.More importantly,the density of oxygen atoms and ozone will increase greatly with increasing oxygen content,which is of great significance for industrial applications.展开更多
Simulations are conducted on capacitively coupled Ar/O_(2)mixed gas discharges employing a one-dimensional fluid coupled with an electron Monte Carlo(MC)model.The research explores the impact of different O_(2)ratio a...Simulations are conducted on capacitively coupled Ar/O_(2)mixed gas discharges employing a one-dimensional fluid coupled with an electron Monte Carlo(MC)model.The research explores the impact of different O_(2)ratio and pressures on the discharge characteristics of Ar/O_(2)plasma.At a fixed Ar/O_(2)gas ratio,with the increasing pressure,higher ion densities,as well as a slight increase in electron density in the bulk region can be observed.The discharge remains dominated by the drift-ambipolar(DA)mode,and the flux of O(3P)at the electrode increases with the increasing pressure due to higher background gas density,while the fluxes of O(1D)and Ardecrease due to the pronounced loss rate.With the increasing proportion of O_(2),a change in the dominant discharge mode from a mode to DA mode can be detected,and the O_(2)-associated charged particle densities are significantly increased.However,Ar+density shows a trend of increasing and then decreasing,while for neutral fluxes at the electrode,Arflux decreases,and O(3P)flux increases with the reduced Ar gas proportion,while trends in O(1D)flux show slight differences.The evolution of the densities of the charged particle and the neutral fluxes under different discharge parameters are discussed in detail using the ionization characteristics as well as the transport properties.Hopefully,more comprehensive understanding of Ar/O_(2)discharge characteristics in this work will provide a valuable reference for the industry.展开更多
群落净生产力(Net Community Production,NCP)代表了总初级生产力与群落呼吸的差值,是衡量生物活动对上层海洋碳循环影响的重要指标。O_(2)/Ar比值消除了物理过程对海水中溶解氧(O_(2))饱和度的影响,因此基于生物氧饱和度(ΔO_(2)/Ar)...群落净生产力(Net Community Production,NCP)代表了总初级生产力与群落呼吸的差值,是衡量生物活动对上层海洋碳循环影响的重要指标。O_(2)/Ar比值消除了物理过程对海水中溶解氧(O_(2))饱和度的影响,因此基于生物氧饱和度(ΔO_(2)/Ar)可以估算海洋混合层群落净生产力。本研究于2015年10月,首次利用膜进样质谱法走航获取了黄东海表层海水中高分辨率O_(2)/Ar数据,并估算了其NCP,探讨了其分布特征及影响因素。本航次观测到的Δ(O_(2)/Ar)范围为-30.21%~44.38%,平均值为(0.32±8.29)%,低值主要出现在长江口北侧,而长江口(11.75±13.75)%和浙闽沿岸(5.42±5.21)%的Δ(O_(2)/Ar)明显高于南黄海(-2.62±5.96)%和东海陆架区(-0.79±5.02)%。南黄海和东海陆架区平均NCP为(-9.24±23.15)和(-4.04±18.68)mmol·m^(-2)·d^(-1),总体表现为异养状态,而长江口和浙闽近岸NCP均值分别为(24.49±35.74)和(10.85±12.17)mmol·m^(-2)·d^(-1)。东、黄海NCP的空间分布格局主要受到陆源输入和水团混合的影响,营养盐和光照也是秋季影响NCP分布的重要因素。本研究有助于深入认识高度动态的东、黄海碳循环过程及控制机制。展开更多
Radio frequency capacitively coupled plasmas(RF CCPs)play a pivotal role in various applications in etching and deposition processes on a microscopic scale in semiconductor manufacturing.In the discharge process,the p...Radio frequency capacitively coupled plasmas(RF CCPs)play a pivotal role in various applications in etching and deposition processes on a microscopic scale in semiconductor manufacturing.In the discharge process,the plasma series resonance(PSR)effect is easily observed in electrically asymmetric and geometrically asymmetric discharges,which could largely influence the power absorption,ionization rate,etc.In this work,the PSR effect arising from geometrically and electrically asymmetric discharge in argon-oxygen mixture gas is mainly investigated by using a plasma equivalent circuit model coupled with a global model.At relatively low pressures,as Ar content(α)increases,the inductance of the bulk is weakened,which leads to a more obvious PSR phenomenon and a higher resonance frequency(ω_(psr)).When the Ar content is fixed,varying the pressure and gap distance could also have different effects on the PSR effect.With the increase of the pressure,the PSR frequency shifts towards the higher order,but in the case of much higher pressure,the PSR oscillation would be strongly damped by frequent electron-neutral collisions.With the increase of the gap distance,the PSR frequency becomes lower.In addition,electrically asymmetric waveforms applied to a geometrically asymmetric chamber may weaken or enhance the asymmetry of the discharge and regulate the PSR effect.In this work,the Ar/O_(2) electronegative mixture gas is introduced in a capacitive discharge to study the PSR effect under geometric asymmetry effect and electrical asymmetry effect,which can provide necessary guidance in laboratory research and current applications.展开更多
基金supported by National Cancer Institute grants R00CA175189,R01AI155499(both to SHO),R01CA205246(to EAR),R01CA121044(to KPL),T32CA085183(to GAH and MML),and P30CA016056,involving the use of the Roswell Park Comprehensive Cancer Center Flow and Image Cytometry,Genomics,Laboratory Animal,and Immune Analysis Shared Resourcesby the Roswell Park Alliance Foundation.NMR experiments were carried out at the Center for Environmental and Systems Biochemistry Shared Resource Facility funded in part by the Markey Cancer Center(P30CA177558).
文摘Metabolic flexibility has emerged as a critical determinant of CD8+T-cell antitumor activity,yet the mechanisms driving the metabolic flexibility of T cells have not been determined.In this study,we investigated the influence of the nuclear cap-binding complex(CBC)adaptor protein ARS2 on mature T cells.In doing so,we discovered a novel signaling axis that endows activated CD8+T cells with flexibility of glucose catabolism.ARS2 upregulation driven by CD28 signaling reinforced splicing factor recruitment to pre-mRNAs and affected approximately one-third of T-cell activation-induced alternative splicing events.Among these effects,the CD28-ARS2 axis suppressed the expression of the M1 isoform of pyruvate kinase in favor of PKM2,a key determinant of CD8+T-cell glucose utilization,interferon gamma production,and antitumor effector function.Importantly,PKM alternative splicing occurred independently of CD28-driven PI3K pathway activation,revealing a novel means by which costimulation reprograms glucose metabolism in CD8+T cells.
基金supported by National Natural Science Foundation of China(Nos.11805107 and 12275039)the Fundamental Research Funds in Heilongjiang Provincial Universities of China(No.145309625)。
文摘In this work,the effects of the frequency,pressure,gas composition,and secondary-electron emission coefficient on the discharge mode in capacitively coupled Ar/O_(2) plasmas were carefully studied through simulations.Three discharge modes,i.e.,α,γ,and drift-ambipolar(DA),were considered in this study.The results show that a mode transition from theγ-DA hybrid mode dominated by theγmode to the DA-αhybrid mode dominated by the DA mode is induced by increasing the frequency from 100 k Hz to 40 MHz.Furthermore,the electron temperature decreases with increasing frequency,while the plasma density first decreases and then increases.It was found that the electronegativity increases slightly with increasing pressure in the lowfrequency region,and it increases notably with increasing pressure in the high-frequency region.It was also observed that the frequency corresponding to the mode transition fromγto DA decreased when the secondary-electron emission coefficient was decreased.Finally,it was found that increasing the oxygen content weakens theγmode and enhances the DA mode.More importantly,the density of oxygen atoms and ozone will increase greatly with increasing oxygen content,which is of great significance for industrial applications.
基金the National Natural Science Foun-dation of China(Grant Nos.12020101005,11975067,and 12347131)the Fundamental Research Funds for the Cen-tral Universities(Grant No.DUT24BS069).
文摘Simulations are conducted on capacitively coupled Ar/O_(2)mixed gas discharges employing a one-dimensional fluid coupled with an electron Monte Carlo(MC)model.The research explores the impact of different O_(2)ratio and pressures on the discharge characteristics of Ar/O_(2)plasma.At a fixed Ar/O_(2)gas ratio,with the increasing pressure,higher ion densities,as well as a slight increase in electron density in the bulk region can be observed.The discharge remains dominated by the drift-ambipolar(DA)mode,and the flux of O(3P)at the electrode increases with the increasing pressure due to higher background gas density,while the fluxes of O(1D)and Ardecrease due to the pronounced loss rate.With the increasing proportion of O_(2),a change in the dominant discharge mode from a mode to DA mode can be detected,and the O_(2)-associated charged particle densities are significantly increased.However,Ar+density shows a trend of increasing and then decreasing,while for neutral fluxes at the electrode,Arflux decreases,and O(3P)flux increases with the reduced Ar gas proportion,while trends in O(1D)flux show slight differences.The evolution of the densities of the charged particle and the neutral fluxes under different discharge parameters are discussed in detail using the ionization characteristics as well as the transport properties.Hopefully,more comprehensive understanding of Ar/O_(2)discharge characteristics in this work will provide a valuable reference for the industry.
文摘群落净生产力(Net Community Production,NCP)代表了总初级生产力与群落呼吸的差值,是衡量生物活动对上层海洋碳循环影响的重要指标。O_(2)/Ar比值消除了物理过程对海水中溶解氧(O_(2))饱和度的影响,因此基于生物氧饱和度(ΔO_(2)/Ar)可以估算海洋混合层群落净生产力。本研究于2015年10月,首次利用膜进样质谱法走航获取了黄东海表层海水中高分辨率O_(2)/Ar数据,并估算了其NCP,探讨了其分布特征及影响因素。本航次观测到的Δ(O_(2)/Ar)范围为-30.21%~44.38%,平均值为(0.32±8.29)%,低值主要出现在长江口北侧,而长江口(11.75±13.75)%和浙闽沿岸(5.42±5.21)%的Δ(O_(2)/Ar)明显高于南黄海(-2.62±5.96)%和东海陆架区(-0.79±5.02)%。南黄海和东海陆架区平均NCP为(-9.24±23.15)和(-4.04±18.68)mmol·m^(-2)·d^(-1),总体表现为异养状态,而长江口和浙闽近岸NCP均值分别为(24.49±35.74)和(10.85±12.17)mmol·m^(-2)·d^(-1)。东、黄海NCP的空间分布格局主要受到陆源输入和水团混合的影响,营养盐和光照也是秋季影响NCP分布的重要因素。本研究有助于深入认识高度动态的东、黄海碳循环过程及控制机制。
基金Project supported by the National Natural Science Foundation of China (Grant Nos.12020101005 and 11975067)。
文摘Radio frequency capacitively coupled plasmas(RF CCPs)play a pivotal role in various applications in etching and deposition processes on a microscopic scale in semiconductor manufacturing.In the discharge process,the plasma series resonance(PSR)effect is easily observed in electrically asymmetric and geometrically asymmetric discharges,which could largely influence the power absorption,ionization rate,etc.In this work,the PSR effect arising from geometrically and electrically asymmetric discharge in argon-oxygen mixture gas is mainly investigated by using a plasma equivalent circuit model coupled with a global model.At relatively low pressures,as Ar content(α)increases,the inductance of the bulk is weakened,which leads to a more obvious PSR phenomenon and a higher resonance frequency(ω_(psr)).When the Ar content is fixed,varying the pressure and gap distance could also have different effects on the PSR effect.With the increase of the pressure,the PSR frequency shifts towards the higher order,but in the case of much higher pressure,the PSR oscillation would be strongly damped by frequent electron-neutral collisions.With the increase of the gap distance,the PSR frequency becomes lower.In addition,electrically asymmetric waveforms applied to a geometrically asymmetric chamber may weaken or enhance the asymmetry of the discharge and regulate the PSR effect.In this work,the Ar/O_(2) electronegative mixture gas is introduced in a capacitive discharge to study the PSR effect under geometric asymmetry effect and electrical asymmetry effect,which can provide necessary guidance in laboratory research and current applications.
