The heavy-ion accelerator facility(HIAF)under construction in China will produce various stable and intense radioactive beams with energies ranging from MeV/u to GeV/u.The ion-linac(iLinac)accelerator,which will serve...The heavy-ion accelerator facility(HIAF)under construction in China will produce various stable and intense radioactive beams with energies ranging from MeV/u to GeV/u.The ion-linac(iLinac)accelerator,which will serve as the injector for the HIAF,is a superconducting heavy-ion accelerator containing 13 cryomodules.It will operate in either continuous wave mode or pulsed mode,with a beam current ranging from 0.01 to 1 emA.The beam position monitor(BPM)is crucial for this high-beam-power machine,which requires precise beam control and a very small beam loss of less than 1 W/m,especially inside the cryomodules of this unique beam instrument.Nearly 70 BPMs will be installed on the iLinac.New digital beam position and phase measurement(DBPPM)electronics based on a heterogeneous multiprocessing platform system-on-chip(MPSoC)has been developed to provide accurate beam trajectory and phase measurements as well as beam interlocking signals for a fast machine protection system(MPS).The DBPPM comprises an analog front-end(AFE)board in field programmable gate array(FPGA)mezzanine-connector(FMC)form factor,along with a digital signal processing board housed within a “2U 19”chassis.To mitigate radio frequency(RF)leakage effects from high-power RF systems in certain scenarios,beam signals undergo simultaneous processing at both fundamental and second-harmonic frequencies.A dynamic range from-65 dBm to 0 dBm was established to accommodate both weak beam commissioning and high-intensity operational demands.Laboratory tests demonstrated that at input power levels exceeding-45 d Bm,the phase resolution surpasses 0.05°,and the position resolution exceeds 5μm.These results align well with the stipulated measurement requirements.Moreover,the newly developed DBPPM has self-testing and self-calibration functions that are highly helpful for the systematic evaluation of numerous electronic components and fault diagnosis equipment.In addition,the DBPPM electronics implements a 2D nonlinear polynomial correction on the FPGA and can collect accurate real-time position measurements at large beam offsets.This newly developed DBPPM electronics has been applied to several Linac machines,and the results from beam measurements show high performance,good long-term stability,and high reliability.In this paper,a detailed overview of the architecture,performance,and proof-of-principle measurement of the beams is presented.展开更多
Osteoarthritis(OA)is a degenerative joint disease accompanied with the loss of cartilage and consequent nociceptive symptoms.Normal articular cartilage maintains at aneural state.Neuron guidance factor Semaphorin 3A(S...Osteoarthritis(OA)is a degenerative joint disease accompanied with the loss of cartilage and consequent nociceptive symptoms.Normal articular cartilage maintains at aneural state.Neuron guidance factor Semaphorin 3A(Sema3A)is a membrane-associated secreted protein with chemorepulsive properties for axons.However,the role of Sema3A in articular cartilage is still not clear.In the present studies,we investigated the functions of Sema3A in OA development in mice,non-human primates,and patients with OA.Sema3A has a protective effect on cartilage degradation,validated by the organoid culture in vitro and confirmed in chondrocyte-specific Sema3A conditional knockout mice.We demonstrated that Sema3A is a key molecule in maintaining cartilage homeostasis from chondrocyte hypertrophy via activating the PI3K pathway.The potential usage of Sema3A for OA treatment was validated in mouse and Rhesus macaque OA models through intra-articular injection of Sema3A,and also in patients by administering Sema3A containing platelet-rich plasma into the knee joints.Our studies demonstrated that Sema3A exerts a critical role in inhibiting neurite ingrowth and preventing chondrocyte hypertrophy in cartilage,and could be potentially used for OA treatment.展开更多
A noninvasive Ionization profile monitor(IPM)consisting of micro-channel plates,a phosphor screen and the optical-signal acquisition has been developed at the cooling storage ring of Heavy Ion Research Facility in Lan...A noninvasive Ionization profile monitor(IPM)consisting of micro-channel plates,a phosphor screen and the optical-signal acquisition has been developed at the cooling storage ring of Heavy Ion Research Facility in Lanzhou(HIRFL-CSR).It makes the real-time profile measurements for the transverse beam cooling and orbit oscillation possible and efficient.This paper firstly describes all the IPM design criterions including the theoretical signal yield calculation,the space charge field and initial momentum evaluation,and the electrostatic field distortion simulation as well.In order to investigate the IPM performance,the beam profile measurements are done with different high voltage settings.Subsequently,some valuable beam experiments about the transverse electron cooling and orbit oscillation study are also presented.In the end,fast turn-by-turn profile measurements for the emittance blow-up research in a synchrotron are discussed.In cooperation with the newly deployed emittance instruments at the HIRFL-CSR injector,the IPM shows great prospects for the injection mismatch study,and potential values for the tune,dispersion and chromaticity measurements as well.展开更多
Osteoarthritis(OA)is the most prevalent joint disorder occurring with articular cartilage degradation.It includes a switch from an articularto a growth plate chondrocyte phenotype.Here,we investigated the histone modi...Osteoarthritis(OA)is the most prevalent joint disorder occurring with articular cartilage degradation.It includes a switch from an articularto a growth plate chondrocyte phenotype.Here,we investigated the histone modification profiles and found significant H3K27me3 loss inOA,which led to disease-associated gene expression.Surprisingly,these genes were occupied by both H3K27me3 and H3K4me3 in normalchondrocytes,showing a poised bivalent state.Furthermore,we observed the derepression of similar bivalent genes in growth platechondrocytes.Finally,a KDM6B inhibitor GSK-J4 prevented the H3K27me3 loss and cartilage damage in the rat OA model.Our resultsreveal an inherited bivalent epigenetic signature on developmental genes that makes articular chondrocytes prone to hypertrophy andcontributes to a promising epigenetic therapy for OA.展开更多
基金supported by the National Natural Science Foundation of China(No.11975290)。
文摘The heavy-ion accelerator facility(HIAF)under construction in China will produce various stable and intense radioactive beams with energies ranging from MeV/u to GeV/u.The ion-linac(iLinac)accelerator,which will serve as the injector for the HIAF,is a superconducting heavy-ion accelerator containing 13 cryomodules.It will operate in either continuous wave mode or pulsed mode,with a beam current ranging from 0.01 to 1 emA.The beam position monitor(BPM)is crucial for this high-beam-power machine,which requires precise beam control and a very small beam loss of less than 1 W/m,especially inside the cryomodules of this unique beam instrument.Nearly 70 BPMs will be installed on the iLinac.New digital beam position and phase measurement(DBPPM)electronics based on a heterogeneous multiprocessing platform system-on-chip(MPSoC)has been developed to provide accurate beam trajectory and phase measurements as well as beam interlocking signals for a fast machine protection system(MPS).The DBPPM comprises an analog front-end(AFE)board in field programmable gate array(FPGA)mezzanine-connector(FMC)form factor,along with a digital signal processing board housed within a “2U 19”chassis.To mitigate radio frequency(RF)leakage effects from high-power RF systems in certain scenarios,beam signals undergo simultaneous processing at both fundamental and second-harmonic frequencies.A dynamic range from-65 dBm to 0 dBm was established to accommodate both weak beam commissioning and high-intensity operational demands.Laboratory tests demonstrated that at input power levels exceeding-45 d Bm,the phase resolution surpasses 0.05°,and the position resolution exceeds 5μm.These results align well with the stipulated measurement requirements.Moreover,the newly developed DBPPM has self-testing and self-calibration functions that are highly helpful for the systematic evaluation of numerous electronic components and fault diagnosis equipment.In addition,the DBPPM electronics implements a 2D nonlinear polynomial correction on the FPGA and can collect accurate real-time position measurements at large beam offsets.This newly developed DBPPM electronics has been applied to several Linac machines,and the results from beam measurements show high performance,good long-term stability,and high reliability.In this paper,a detailed overview of the architecture,performance,and proof-of-principle measurement of the beams is presented.
基金partly National Key R&D Program of China(2023YFA1801200,2023YFA1801202)Major Program of the National Natural Science Foundation of China(T2394532)+6 种基金National Natural Science Foundation of China(82072489)The Foundation of Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions(NYKFKT2019007)Shenzhen Medical Research Fund(B2302011)The Sanming Project of Medicine in Shenzhen(SZZYSM202311013)The China Postdoctoral Science Foundational,2023M743679Shenzhen Science and Technology Research Funding(JCYJ20220818101414032)Key Research Project of Science&Technology Department of Sichuan Province,China(2024YFFK0041)。
文摘Osteoarthritis(OA)is a degenerative joint disease accompanied with the loss of cartilage and consequent nociceptive symptoms.Normal articular cartilage maintains at aneural state.Neuron guidance factor Semaphorin 3A(Sema3A)is a membrane-associated secreted protein with chemorepulsive properties for axons.However,the role of Sema3A in articular cartilage is still not clear.In the present studies,we investigated the functions of Sema3A in OA development in mice,non-human primates,and patients with OA.Sema3A has a protective effect on cartilage degradation,validated by the organoid culture in vitro and confirmed in chondrocyte-specific Sema3A conditional knockout mice.We demonstrated that Sema3A is a key molecule in maintaining cartilage homeostasis from chondrocyte hypertrophy via activating the PI3K pathway.The potential usage of Sema3A for OA treatment was validated in mouse and Rhesus macaque OA models through intra-articular injection of Sema3A,and also in patients by administering Sema3A containing platelet-rich plasma into the knee joints.Our studies demonstrated that Sema3A exerts a critical role in inhibiting neurite ingrowth and preventing chondrocyte hypertrophy in cartilage,and could be potentially used for OA treatment.
基金This work was supported by the National Natural Science Foundation of China(No.11805250).
文摘A noninvasive Ionization profile monitor(IPM)consisting of micro-channel plates,a phosphor screen and the optical-signal acquisition has been developed at the cooling storage ring of Heavy Ion Research Facility in Lanzhou(HIRFL-CSR).It makes the real-time profile measurements for the transverse beam cooling and orbit oscillation possible and efficient.This paper firstly describes all the IPM design criterions including the theoretical signal yield calculation,the space charge field and initial momentum evaluation,and the electrostatic field distortion simulation as well.In order to investigate the IPM performance,the beam profile measurements are done with different high voltage settings.Subsequently,some valuable beam experiments about the transverse electron cooling and orbit oscillation study are also presented.In the end,fast turn-by-turn profile measurements for the emittance blow-up research in a synchrotron are discussed.In cooperation with the newly deployed emittance instruments at the HIRFL-CSR injector,the IPM shows great prospects for the injection mismatch study,and potential values for the tune,dispersion and chromaticity measurements as well.
基金supported by the National Natural Science Foundation of China(U22A20280,81874027)Science&Technology Department of Sichuan Province(2023NSFSC1607,2021YFSY0003,2022YFS0051,2022NSFSC1312)+1 种基金Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions(312200102)Clinical Research Incubation project of West China Hospital of Sichuan University(2021HXFH036)。
文摘Osteoarthritis(OA)is the most prevalent joint disorder occurring with articular cartilage degradation.It includes a switch from an articularto a growth plate chondrocyte phenotype.Here,we investigated the histone modification profiles and found significant H3K27me3 loss inOA,which led to disease-associated gene expression.Surprisingly,these genes were occupied by both H3K27me3 and H3K4me3 in normalchondrocytes,showing a poised bivalent state.Furthermore,we observed the derepression of similar bivalent genes in growth platechondrocytes.Finally,a KDM6B inhibitor GSK-J4 prevented the H3K27me3 loss and cartilage damage in the rat OA model.Our resultsreveal an inherited bivalent epigenetic signature on developmental genes that makes articular chondrocytes prone to hypertrophy andcontributes to a promising epigenetic therapy for OA.
