AI development has brought great success to upgrading the information age.At the same time,the large-scale artificial neural network for building AI systems is thirsty for computing power,which is barely satisfied by ...AI development has brought great success to upgrading the information age.At the same time,the large-scale artificial neural network for building AI systems is thirsty for computing power,which is barely satisfied by the conventional computing hardware.In the post-Moore era,the increase in computing power brought about by the size reduction of CMOS in very large-scale integrated circuits(VLSIC)is challenging to meet the growing demand for AI computing power.To address the issue,technical approaches like neuromorphic computing attract great attention because of their feature of breaking Von-Neumann architecture,and dealing with AI algorithms much more parallelly and energy efficiently.Inspired by the human neural network architecture,neuromorphic computing hardware is brought to life based on novel artificial neurons constructed by new materials or devices.Although it is relatively difficult to deploy a training process in the neuromorphic architecture like spiking neural network(SNN),the development in this field has incubated promising technologies like in-sensor computing,which brings new opportunities for multidisciplinary research,including the field of optoelectronic materials and devices,artificial neural networks,and microelectronics integration technology.The vision chips based on the architectures could reduce unnecessary data transfer and realize fast and energy-efficient visual cognitive processing.This paper reviews firstly the architectures and algorithms of SNN,and artificial neuron devices supporting neuromorphic computing,then the recent progress of in-sensor computing vision chips,which all will promote the development of AI.展开更多
Growth of gallium nitride(GaN)inverted pyramids on c-plane sapphire substrates is benefit for fabricating novel devices as it forms the semipolar facets.In this work,GaN inverted pyramids are directly grown on c-plane...Growth of gallium nitride(GaN)inverted pyramids on c-plane sapphire substrates is benefit for fabricating novel devices as it forms the semipolar facets.In this work,GaN inverted pyramids are directly grown on c-plane patterned sapphire substrates(PSS)by metal organic vapor phase epitaxy(MOVPE).The influences of growth conditions on the surface morphol-ogy are experimentally studied and explained by Wulff constructions.The competition of growth rate among{0001},{1011},and{1122}facets results in the various surface morphologies of GaN.A higher growth temperature of 985 ℃ and a lowerⅤ/Ⅲratio of 25 can expand the area of{}facets in GaN inverted pyramids.On the other hand,GaN inverted pyramids with almost pure{}facets are obtained by using a lower growth temperature of 930℃,a higherⅤ/Ⅲratio of 100,and PSS with pattern arrangement perpendicular to the substrate primary flat.展开更多
This paper presents a wide-bandwidth back-illuminated modified uni-traveling-carrier photodiode(MUTC-PD)packaged with standard WR-5 rectangular waveguide for high-speed wireless communications.With optimized epitaxy s...This paper presents a wide-bandwidth back-illuminated modified uni-traveling-carrier photodiode(MUTC-PD)packaged with standard WR-5 rectangular waveguide for high-speed wireless communications.With optimized epitaxy structure and coplanar waveguide electrodes,the fabricated 4-μm-diameter PD exhibits ultra-flat frequency response and high saturation power.Integrated passive circuits including low-loss bias-tee and E-plane probe are designed to package the PD into a compact module with waveguide output.The packaged PD module has demonstrated a flat frequency response with fluctuations within±2.75 d B over a broadband of 140–220 GHz and a high saturated output power of-7.8 d Bm(166μW)at 140 GHz.For wireless communication applications,the packaged PD is used to implement 1-m free space transmission at carrier frequencies of 150.5 and 210.5 GHz,with transmission rates of 75 and 90 Gbps,respectively.展开更多
The growing trend of network virtualization results in a widespread adoption of virtual switches in virtualized environments. However, virtual switching is confronted with great performance challenges regarding packet...The growing trend of network virtualization results in a widespread adoption of virtual switches in virtualized environments. However, virtual switching is confronted with great performance challenges regarding packet classification especially in Open Flow-based software defined networks. This paper first takes an insight into packet classification in virtual Open Flow switching, and points out that its performance bottleneck is dominated by flow table traversals of multiple failed mask probing for each arrived packet. Then we are motivated to propose an efficient packet classification algorithm based on counting bloom filters. In particular, counting bloom filters are applied to predict the failures of flow table lookups with great possibilities, and bypass flow table traversals for failed mask probing. Finally, our proposed packet classification algorithm is evaluated with real network traffic traces by experiments. The experimental results indicate that our proposed algorithm outperforms the classical one in Open v Switch in terms of average search length, and contributes to promote virtual Open Flow switching performance.展开更多
GaN and AlN nanowires(NWs) have attracted great interests for the fabrication of novel nano-sized devices. In this paper, the nucleation processes of GaN and AlN NWs grown on Si substrates by molecular beam epitaxy...GaN and AlN nanowires(NWs) have attracted great interests for the fabrication of novel nano-sized devices. In this paper, the nucleation processes of GaN and AlN NWs grown on Si substrates by molecular beam epitaxy(MBE)are investigated. It is found that GaN NWs nucleated on in-situ formed Si3N4 fully release the stress upon the interface between GaN NW and amorphous Si3N4 layer, while AlN NWs nucleated by aluminization process gradually release the stress during growth. Depending on the strain status as well as the migration ability of Ⅲ group adatoms, the different growth kinetics of GaN and AlN NWs result in different NW morphologies, i.e., GaN NWs with uniform radii and AlN NWs with tapered bases.展开更多
A novel backside-illuminated double-cliff-layer uni-traveling-carrier(DCL-UTC)photodiode with both high responsivity and ultra-broad bandwidth is designed and demonstrated.A thick absorption layer is adopted for high ...A novel backside-illuminated double-cliff-layer uni-traveling-carrier(DCL-UTC)photodiode with both high responsivity and ultra-broad bandwidth is designed and demonstrated.A thick absorption layer is adopted for high responsivity,and a depletion region with double cliff layers is proposed to alleviate the space charge effect and maintain overshoot electron velocity under large photocurrents.In addition,inductive coplanar waveguide electrodes are employed to enhance the frequency response performance.The 6-μm-diameter photodiode exhibits a high responsivity of 0.51 A/W and a large 3-dB bandwidth of 102 GHz.A high RF output power of 2.7 dBm is recorded at 100 GHz.展开更多
The important role of immunogenic cell death(ICD)in many tumors is increasingly being discovered.However,its mechanisms and potential as a biomarker and therapeutic target in glioblastoma(GBM)have not been well studie...The important role of immunogenic cell death(ICD)in many tumors is increasingly being discovered.However,its mechanisms and potential as a biomarker and therapeutic target in glioblastoma(GBM)have not been well studied.We obtained GBM samples from the Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)databases,as well as the immunotherapy cohort from the IMvigor210 study.We used unsupervised clustering to obtain two ICDrelated clusters,corresponding to the ICD-low and ICD-high subtypes respectively,and the tumor immune microenvironment and prognosis of the two subtypes were significantly different.展开更多
Histone acetylation is a critical process in the regulation of chromatin structure and gene expression.Histone deacetylases(HDACs)remove the acetyl group,leading to chromatin condensation and transcriptional repressio...Histone acetylation is a critical process in the regulation of chromatin structure and gene expression.Histone deacetylases(HDACs)remove the acetyl group,leading to chromatin condensation and transcriptional repression.HDAC inhibitors are considered a new class of anticancer agents and have been shown to alter gene transcription and exert antitumor effects.This paper describes our work on the structural determination and structure-activity relationship(SAR)optimization of tetrahydroisoquinoline compounds as HDAC inhibitors.These compounds were tested for their ability to inhibit HDAC 1,3,6 and for their ability to inhibit the proliferation of a panel of cancer cell lines.Among these,compound 82 showed the greatest inhibitory activity toward HDAC 1,3,6 and strongly inhibited growth of the cancer cell lines,with results clearly superior to those of the reference compound,vorinostat(SAHA).Compound 82 increased the acetylation of histones H3,H4 and tubulin in a concentration-dependent manner,suggesting that it is a broad inhibitor of HDACs.展开更多
Genomic alterations are commonly found in the signaling pathways of fibroblast growth factor receptors(FGFRs). Although there is no selective FGFR inhibitors in market, several promising inhibitors have been investiga...Genomic alterations are commonly found in the signaling pathways of fibroblast growth factor receptors(FGFRs). Although there is no selective FGFR inhibitors in market, several promising inhibitors have been investigated in clinical trials, and showed encouraging efficacies in patients. By designing a hybrid between the FGFR-selectivity-enhancing motif dimethoxybenzene group and our previously identified novel scaffold, we discovered a new series of potent FGFR inhibitors, with the best one showing sub-nanomolar enzymatic activity. After several round of optimization and with the solved crystal structure, detailed structure–activity relationship was elaborated. Together with in vitro metabolic stability tests and in vivo pharmacokinetic profiling, a representative compound(35) was selected and tested in xenograft mouse model, and the result demonstrated that inhibitor 35 was effective against tumors with FGFR genetic alterations, exhibiting potential for further development.展开更多
A novel thin-film lithium niobate(TFLN) electro-optic modulator is proposed and demonstrated. LiNbO_(3)-silica hybrid waveguide is adopted to maintain low optical loss for an electrode spacing as narrow as 3 μm, resu...A novel thin-film lithium niobate(TFLN) electro-optic modulator is proposed and demonstrated. LiNbO_(3)-silica hybrid waveguide is adopted to maintain low optical loss for an electrode spacing as narrow as 3 μm, resulting in a low halfwave-voltage length product of only 1.7 V·cm. Capacitively loaded traveling-wave electrodes are employed to reduce the microwave loss, while a quartz substrate is used in place of a silicon substrate to achieve velocity matching. The fabricated TFLN modulator with a 5-mm-long modulation region exhibits a half-wave voltage of 3.4 V and a merely less than 2 d B roll-off in an electro-optic response up to 67 GHz.展开更多
Transverse pressure gradient(TPG)is one of the key factors influencing the boundary layer airflow diversion in a bump inlet.This paper proposes a novel TPG-based hypersonic bump inlet design method.This method consist...Transverse pressure gradient(TPG)is one of the key factors influencing the boundary layer airflow diversion in a bump inlet.This paper proposes a novel TPG-based hypersonic bump inlet design method.This method consists of two steps.First,a parametric optimization approach is employed to design a series of 2D inlets with various compression efficiencies.Then,according to the prescribed TPG,the optimized inlets are placed in different osculating planes to generate a 3D bump inlet.This method provides a means to directly control the aerodynamic parameters of the bump rather than the geometric parameters.By performing this method to a hypersonic chin inlet,a long and wide bump surface is formed in the compression wall,which leads to good integration of the bump/inlet.Results show that a part of the near-wall boundary layer flow is diverted by the bump,resulting in a slight decrease in the mass flow but a significant improvement in the total pressure recovery.In addition,the starting ability is significantly improved by adding the bump surface.Analysis reveals that the bump has a 3D rebuilding effect on the large-scale separation bubble of the unstarted inlet.Finally,a mass flow correction is performed on the designed bump inlet to increase the mass flow to full airflow capture.The results show that the mass flow rate of the corrected bump inlet reaches up to 0.9993,demonstrating that the correction method is effective.展开更多
Laser annealing of silicon dioxide (SiO2) film formed by inductively coupled plasma enhanced chemical vapor deposition (ICPECVD)is studied for the fabrication of low loss silicon based waveguide. The influence of ...Laser annealing of silicon dioxide (SiO2) film formed by inductively coupled plasma enhanced chemical vapor deposition (ICPECVD)is studied for the fabrication of low loss silicon based waveguide. The influence of laser annealing on ICPECVD-deposited SiO2 film is investigated. The surface roughness, refractive index, and etch rate of annealed samples are compared with those of SiO2 film obtained by thermal oxidation. It is demonstrated that the performance of ICPECVD-deposited SiO2 film can be significantly improved by laser annealing. Al2O3/SIO2 waveguide has been fabricated on silicon substrate with the SiO2 lower cladding formed by ICPECVD and laser annealing process, and its propagation loss is found to be comparable with that of the waveguide with thermally oxidized lower cladding.展开更多
Objective: The aim of the present study was to examine dynamic changes in serum cholinesterase (ChE) activity during early-stage severe trauma and the clinical significance of these changes. Methods: This prospect...Objective: The aim of the present study was to examine dynamic changes in serum cholinesterase (ChE) activity during early-stage severe trauma and the clinical significance of these changes. Methods: This prospective, observational study included 81 patients with severe trauma who were treated between October 2011 and April 2013 in the emergency intensive care unit (EICU) of a university-affiliated, tertiary-care, grade A general hospital in China. Serum ChE activity was measured on Days 1, 3, and 7 post-injury. The correlation of dynamic changes in serum ChE activity with trauma severity and prognosis was assessed. Correlations between changes in serum ChE activity after injury and albumin (ALB), prealbumin (PAB), transferrin (TRF), and C-reactive protein (CRP) levels were also analyzed Results: Serum ChE activity in trauma patients was 42.3%-50.2% lower on Days 1, 3, and 7 compared with the control (P〈0.001 for all time points), and it continued to decrease after Day 7 in both the survival and death subgroups. In the subgroup with an injury severity score (ISS) of 〈25, serum ChE activity initially decreased, but eventually increased. However, activity decreased continuously in the ISS〉25 subgroup. ChE activity was significantly lower in both the death and the ISS〉25 subgroups than in the survival and ISS〈25 subgroups on Days 1, 3, and 7 after injury. Activity was negatively correlated with ISS and acute physiology and chronic health evaluation Ill (APACHE III) at all time points. When comparing the receiver operating characteristic (ROC) curves for predicting prognosis, the area under the curve (AUC) in the dot of serum ChE was similar to the AUCs in plots of ISS and APACHE Ⅲ, but significantly smaller than the AUC in the plot of the trauma and injury severity score (TRISS). Serum ChE activity was positively correlated with ALB, PAB, and TRF at all time points post-injury. Activity was not significantly correlated with CRP on Day 1, but was significantly and negatively correlated with CRP on Days 3 and 7. Conclusions: There is a significant decrease in serum ChE activity after severe trauma. Serum ChE may be regarded as a negative acute phase protein (APP) and the dynamic changes in serum ChE may be useful as an auxiliary indicator for evaluating trauma severity and predicting prognosis.展开更多
Idiopathic pulmonary fibrosis(IPF)is a chronic fatal lung disease with a median survival time of 3–5 years.Inaccurate diagnosis,limited clinical therapy and high mortality together indicate that the development of ef...Idiopathic pulmonary fibrosis(IPF)is a chronic fatal lung disease with a median survival time of 3–5 years.Inaccurate diagnosis,limited clinical therapy and high mortality together indicate that the development of effective therapeutics for IPF is an urgent need.In recent years,it was reported that DDRs are potential targets in anti-fibrosis treatment.Based on previous work we carried out further structure modifications and led to a more selective inhibitor 47 by averting some fibrosis-unrelated kinases,such as RET,AXL and ALK.Extensive profiling of compound 47 has demonstrated that it has potent DDR1/2 inhibitory activities,low toxicity,good pharmacokinetic properties and reliable in vivo anti-fibrosis efficacy.Therefore,we confirmed that discoidin domain receptors are promising drug targets for IPF,and compound 47 would be a promising candidate for further drug development.展开更多
Unstart is an unwanted flow phenomenon in a hypersonic inlet. When an unstart occurs, the captured airflow flowing through the engine significantly decreases with strong unsteady characteristics, which may lead to thr...Unstart is an unwanted flow phenomenon in a hypersonic inlet. When an unstart occurs, the captured airflow flowing through the engine significantly decreases with strong unsteady characteristics, which may lead to thrust loss or even combustor flameout. In this study, various bump configurations were designed to be integrated with a hypersonic inlet to improve its starting ability. A bump was defined as an integrated 3D compression surface installed upstream of the inlet entrance. The starting processes of these bump inlets were numerically simulated to investigate the effect laws and flow mechanisms of the bump parameters. Tests on bump height revealed that the starting performance could be significantly improved by increasing bump height, with the starting Mach number decreasing by 0.55 for the inlet with the highest bump. The high bump facilitates the side movement of the subsonic flow in the separation zone, which leads to a small separation bubble, thus accelerating the starting process. Further, the starting ability can be improved by designing a relatively wide bump, which results in a decline in the starting Mach number by 0.44. When the bump has the same or greater width compared with the airflow capture range, a growing spillage along the transverse direction can be formed so that the airflow in the separation bubble can be easily excluded, improving the starting ability.展开更多
基金Project supported in part by the National Key Research and Development Program of China(Grant No.2021YFA0716400)the National Natural Science Foundation of China(Grant Nos.62225405,62150027,61974080,61991443,61975093,61927811,61875104,62175126,and 62235011)+2 种基金the Ministry of Science and Technology of China(Grant Nos.2021ZD0109900 and 2021ZD0109903)the Collaborative Innovation Center of Solid-State Lighting and Energy-Saving ElectronicsTsinghua University Initiative Scientific Research Program.
文摘AI development has brought great success to upgrading the information age.At the same time,the large-scale artificial neural network for building AI systems is thirsty for computing power,which is barely satisfied by the conventional computing hardware.In the post-Moore era,the increase in computing power brought about by the size reduction of CMOS in very large-scale integrated circuits(VLSIC)is challenging to meet the growing demand for AI computing power.To address the issue,technical approaches like neuromorphic computing attract great attention because of their feature of breaking Von-Neumann architecture,and dealing with AI algorithms much more parallelly and energy efficiently.Inspired by the human neural network architecture,neuromorphic computing hardware is brought to life based on novel artificial neurons constructed by new materials or devices.Although it is relatively difficult to deploy a training process in the neuromorphic architecture like spiking neural network(SNN),the development in this field has incubated promising technologies like in-sensor computing,which brings new opportunities for multidisciplinary research,including the field of optoelectronic materials and devices,artificial neural networks,and microelectronics integration technology.The vision chips based on the architectures could reduce unnecessary data transfer and realize fast and energy-efficient visual cognitive processing.This paper reviews firstly the architectures and algorithms of SNN,and artificial neuron devices supporting neuromorphic computing,then the recent progress of in-sensor computing vision chips,which all will promote the development of AI.
基金the National Key Research and Development Program(2021YFA0716400)the National Natural Science Foundation of China(62225405,62350002,61991443)+1 种基金the Key R&D Project of Jiangsu Province,China(BE2020004)the Collaborative Innovation Centre of Solid-State Lighting and Energy-Saving Electronics.
文摘Growth of gallium nitride(GaN)inverted pyramids on c-plane sapphire substrates is benefit for fabricating novel devices as it forms the semipolar facets.In this work,GaN inverted pyramids are directly grown on c-plane patterned sapphire substrates(PSS)by metal organic vapor phase epitaxy(MOVPE).The influences of growth conditions on the surface morphol-ogy are experimentally studied and explained by Wulff constructions.The competition of growth rate among{0001},{1011},and{1122}facets results in the various surface morphologies of GaN.A higher growth temperature of 985 ℃ and a lowerⅤ/Ⅲratio of 25 can expand the area of{}facets in GaN inverted pyramids.On the other hand,GaN inverted pyramids with almost pure{}facets are obtained by using a lower growth temperature of 930℃,a higherⅤ/Ⅲratio of 100,and PSS with pattern arrangement perpendicular to the substrate primary flat.
基金supported in part by National Key Research and Development Program of China(No.2022YFB2803002)National Natural Science Foundation of China(Nos.62235005,62127814,62225405,61975093,61927811,61991443,61925104 and 61974080)Collaborative Innovation Centre of Solid-State Lighting and Energy-Saving Electronics.
文摘This paper presents a wide-bandwidth back-illuminated modified uni-traveling-carrier photodiode(MUTC-PD)packaged with standard WR-5 rectangular waveguide for high-speed wireless communications.With optimized epitaxy structure and coplanar waveguide electrodes,the fabricated 4-μm-diameter PD exhibits ultra-flat frequency response and high saturation power.Integrated passive circuits including low-loss bias-tee and E-plane probe are designed to package the PD into a compact module with waveguide output.The packaged PD module has demonstrated a flat frequency response with fluctuations within±2.75 d B over a broadband of 140–220 GHz and a high saturated output power of-7.8 d Bm(166μW)at 140 GHz.For wireless communication applications,the packaged PD is used to implement 1-m free space transmission at carrier frequencies of 150.5 and 210.5 GHz,with transmission rates of 75 and 90 Gbps,respectively.
基金supported in part by National Natural Science Foundation of China(61272148,61572525,61502056,and 61602525)Hunan Provincial Natural Science Foundation of China(2015JJ3010)Scientific Research Fund of Hunan Provincial Education Department(15B009,14C0285)
文摘The growing trend of network virtualization results in a widespread adoption of virtual switches in virtualized environments. However, virtual switching is confronted with great performance challenges regarding packet classification especially in Open Flow-based software defined networks. This paper first takes an insight into packet classification in virtual Open Flow switching, and points out that its performance bottleneck is dominated by flow table traversals of multiple failed mask probing for each arrived packet. Then we are motivated to propose an efficient packet classification algorithm based on counting bloom filters. In particular, counting bloom filters are applied to predict the failures of flow table lookups with great possibilities, and bypass flow table traversals for failed mask probing. Finally, our proposed packet classification algorithm is evaluated with real network traffic traces by experiments. The experimental results indicate that our proposed algorithm outperforms the classical one in Open v Switch in terms of average search length, and contributes to promote virtual Open Flow switching performance.
基金supported by the National Basic Research Program of China(Grant No.2013CB632804)the National Natural Science Foundation of China(Grant Nos.61176015,61176059,61210014,61321004,and 61307024)the High Technology Research and Development Program of China(Grant No.2012AA050601)
文摘GaN and AlN nanowires(NWs) have attracted great interests for the fabrication of novel nano-sized devices. In this paper, the nucleation processes of GaN and AlN NWs grown on Si substrates by molecular beam epitaxy(MBE)are investigated. It is found that GaN NWs nucleated on in-situ formed Si3N4 fully release the stress upon the interface between GaN NW and amorphous Si3N4 layer, while AlN NWs nucleated by aluminization process gradually release the stress during growth. Depending on the strain status as well as the migration ability of Ⅲ group adatoms, the different growth kinetics of GaN and AlN NWs result in different NW morphologies, i.e., GaN NWs with uniform radii and AlN NWs with tapered bases.
基金This work was supported in part by the National Key R&D Program of China(No.2022YFB2803002)National Natural Science Foundation of China(Nos.62235005,62127814,62225405,61975093,61927811,61991443,and 61974080)Collaborative Innovation Center of Solid-State Lighting and Energy-Saving Electronics.
文摘A novel backside-illuminated double-cliff-layer uni-traveling-carrier(DCL-UTC)photodiode with both high responsivity and ultra-broad bandwidth is designed and demonstrated.A thick absorption layer is adopted for high responsivity,and a depletion region with double cliff layers is proposed to alleviate the space charge effect and maintain overshoot electron velocity under large photocurrents.In addition,inductive coplanar waveguide electrodes are employed to enhance the frequency response performance.The 6-μm-diameter photodiode exhibits a high responsivity of 0.51 A/W and a large 3-dB bandwidth of 102 GHz.A high RF output power of 2.7 dBm is recorded at 100 GHz.
文摘The important role of immunogenic cell death(ICD)in many tumors is increasingly being discovered.However,its mechanisms and potential as a biomarker and therapeutic target in glioblastoma(GBM)have not been well studied.We obtained GBM samples from the Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)databases,as well as the immunotherapy cohort from the IMvigor210 study.We used unsupervised clustering to obtain two ICDrelated clusters,corresponding to the ICD-low and ICD-high subtypes respectively,and the tumor immune microenvironment and prognosis of the two subtypes were significantly different.
基金supported by the National Natural Science Foundation of China(U2032154)the Key Research and Development Program of Anhui(202004a05020072)+1 种基金Anhui Initiative in Quantum Information Technologies(AHY100000)Anhui Provincial Natural Science Foundation(1908085ME119)。
基金supported financially by the National Science & Technology Major Project ‘Key New Drug Creation and Manufacturing Program’ of China(Grant No.2014ZX09507002)the National Marine ‘863’ Project(No.2013AA092902)
文摘Histone acetylation is a critical process in the regulation of chromatin structure and gene expression.Histone deacetylases(HDACs)remove the acetyl group,leading to chromatin condensation and transcriptional repression.HDAC inhibitors are considered a new class of anticancer agents and have been shown to alter gene transcription and exert antitumor effects.This paper describes our work on the structural determination and structure-activity relationship(SAR)optimization of tetrahydroisoquinoline compounds as HDAC inhibitors.These compounds were tested for their ability to inhibit HDAC 1,3,6 and for their ability to inhibit the proliferation of a panel of cancer cell lines.Among these,compound 82 showed the greatest inhibitory activity toward HDAC 1,3,6 and strongly inhibited growth of the cancer cell lines,with results clearly superior to those of the reference compound,vorinostat(SAHA).Compound 82 increased the acetylation of histones H3,H4 and tubulin in a concentration-dependent manner,suggesting that it is a broad inhibitor of HDACs.
基金financial support from the National Natural Science Foundation of China(Grants No.81661148046 and81773762,China)the "Personalized Medicines-Molecular Signature-based Drug Discovery and Development",Strategic Priority Research Program of the Chinese Academy of Sciences(Grants No.XDA12020317,China)+1 种基金the program for Innovative Research Team of the Ministry of Education(China)the program for Liaoning Innovative Research Team at Shenyang Pharmaceutical University(China)
文摘Genomic alterations are commonly found in the signaling pathways of fibroblast growth factor receptors(FGFRs). Although there is no selective FGFR inhibitors in market, several promising inhibitors have been investigated in clinical trials, and showed encouraging efficacies in patients. By designing a hybrid between the FGFR-selectivity-enhancing motif dimethoxybenzene group and our previously identified novel scaffold, we discovered a new series of potent FGFR inhibitors, with the best one showing sub-nanomolar enzymatic activity. After several round of optimization and with the solved crystal structure, detailed structure–activity relationship was elaborated. Together with in vitro metabolic stability tests and in vivo pharmacokinetic profiling, a representative compound(35) was selected and tested in xenograft mouse model, and the result demonstrated that inhibitor 35 was effective against tumors with FGFR genetic alterations, exhibiting potential for further development.
基金supported in part by the National Key R&D Program of China(No.2018YFB2201701)National Natural Science Foundation of China(Nos.61975093,61927811,61991443,61822404,61974080,61904093,and 61875104)+1 种基金Key Lab Program of BNRist(No.BNR2019ZS01005),China Postdoctoral Science Foundation(No.2019T120090)Collaborative Innovation Centre of Solid-State Lighting and Energy-Saving Electronics。
文摘A novel thin-film lithium niobate(TFLN) electro-optic modulator is proposed and demonstrated. LiNbO_(3)-silica hybrid waveguide is adopted to maintain low optical loss for an electrode spacing as narrow as 3 μm, resulting in a low halfwave-voltage length product of only 1.7 V·cm. Capacitively loaded traveling-wave electrodes are employed to reduce the microwave loss, while a quartz substrate is used in place of a silicon substrate to achieve velocity matching. The fabricated TFLN modulator with a 5-mm-long modulation region exhibits a half-wave voltage of 3.4 V and a merely less than 2 d B roll-off in an electro-optic response up to 67 GHz.
基金the National Natural Science Foundation of China(No.12102470)the Hunan Provincial Innovation Foundation for Postgraduate(No.CX20200082),China。
文摘Transverse pressure gradient(TPG)is one of the key factors influencing the boundary layer airflow diversion in a bump inlet.This paper proposes a novel TPG-based hypersonic bump inlet design method.This method consists of two steps.First,a parametric optimization approach is employed to design a series of 2D inlets with various compression efficiencies.Then,according to the prescribed TPG,the optimized inlets are placed in different osculating planes to generate a 3D bump inlet.This method provides a means to directly control the aerodynamic parameters of the bump rather than the geometric parameters.By performing this method to a hypersonic chin inlet,a long and wide bump surface is formed in the compression wall,which leads to good integration of the bump/inlet.Results show that a part of the near-wall boundary layer flow is diverted by the bump,resulting in a slight decrease in the mass flow but a significant improvement in the total pressure recovery.In addition,the starting ability is significantly improved by adding the bump surface.Analysis reveals that the bump has a 3D rebuilding effect on the large-scale separation bubble of the unstarted inlet.Finally,a mass flow correction is performed on the designed bump inlet to increase the mass flow to full airflow capture.The results show that the mass flow rate of the corrected bump inlet reaches up to 0.9993,demonstrating that the correction method is effective.
基金This work was supported by the National Basic Research Program of China (Nos. 2012CB315605 and 2014CB340002), the National Natural Science Foundation of China (Grant Nos. 61210014,61321004, 61307024, 61574082 and 51561165012), the High Technology Researeh and Development Program of China(No. 2015AA017101), the Independent Research Program of Tsinghua University (No. 20131089364) and the Open Fund of State Key Laboratory on Integrated Optoelectronics (Nos. IOSKL2012KF08 and IOSKL2014KF09).
文摘Laser annealing of silicon dioxide (SiO2) film formed by inductively coupled plasma enhanced chemical vapor deposition (ICPECVD)is studied for the fabrication of low loss silicon based waveguide. The influence of laser annealing on ICPECVD-deposited SiO2 film is investigated. The surface roughness, refractive index, and etch rate of annealed samples are compared with those of SiO2 film obtained by thermal oxidation. It is demonstrated that the performance of ICPECVD-deposited SiO2 film can be significantly improved by laser annealing. Al2O3/SIO2 waveguide has been fabricated on silicon substrate with the SiO2 lower cladding formed by ICPECVD and laser annealing process, and its propagation loss is found to be comparable with that of the waveguide with thermally oxidized lower cladding.
基金Project supported by the Zhejiang Medical and Health Research Project(No.2012KYB092)the Education Department of Zhejiang Province(No.Y201018337)the Science and Technology Department of Zhejiang Province(No.2012C33124),China
文摘Objective: The aim of the present study was to examine dynamic changes in serum cholinesterase (ChE) activity during early-stage severe trauma and the clinical significance of these changes. Methods: This prospective, observational study included 81 patients with severe trauma who were treated between October 2011 and April 2013 in the emergency intensive care unit (EICU) of a university-affiliated, tertiary-care, grade A general hospital in China. Serum ChE activity was measured on Days 1, 3, and 7 post-injury. The correlation of dynamic changes in serum ChE activity with trauma severity and prognosis was assessed. Correlations between changes in serum ChE activity after injury and albumin (ALB), prealbumin (PAB), transferrin (TRF), and C-reactive protein (CRP) levels were also analyzed Results: Serum ChE activity in trauma patients was 42.3%-50.2% lower on Days 1, 3, and 7 compared with the control (P〈0.001 for all time points), and it continued to decrease after Day 7 in both the survival and death subgroups. In the subgroup with an injury severity score (ISS) of 〈25, serum ChE activity initially decreased, but eventually increased. However, activity decreased continuously in the ISS〉25 subgroup. ChE activity was significantly lower in both the death and the ISS〉25 subgroups than in the survival and ISS〈25 subgroups on Days 1, 3, and 7 after injury. Activity was negatively correlated with ISS and acute physiology and chronic health evaluation Ill (APACHE III) at all time points. When comparing the receiver operating characteristic (ROC) curves for predicting prognosis, the area under the curve (AUC) in the dot of serum ChE was similar to the AUCs in plots of ISS and APACHE Ⅲ, but significantly smaller than the AUC in the plot of the trauma and injury severity score (TRISS). Serum ChE activity was positively correlated with ALB, PAB, and TRF at all time points post-injury. Activity was not significantly correlated with CRP on Day 1, but was significantly and negatively correlated with CRP on Days 3 and 7. Conclusions: There is a significant decrease in serum ChE activity after severe trauma. Serum ChE may be regarded as a negative acute phase protein (APP) and the dynamic changes in serum ChE may be useful as an auxiliary indicator for evaluating trauma severity and predicting prognosis.
基金This research has been financially supported by grants from the Strategic Priority Research Program of the Chinese Academy of Sciences(Grant No.XDA12020323)the National Science&Technology Major Project“Key New Drug Creation and Manufacturing Program”of China(Grant No.2018ZX09711002-004-009)+3 种基金the Strategic Priority Research Program of Chinese Academy of Sciences(No.SIMM010203)Institutes for Drug Discovery and Development,Chinese Academy of Sciences(No.CASIMM0120215009)National Natural Science Foundation of China(No.U1703235)Shanghai Science and Technology Development Funds(18431907100,China).
文摘Idiopathic pulmonary fibrosis(IPF)is a chronic fatal lung disease with a median survival time of 3–5 years.Inaccurate diagnosis,limited clinical therapy and high mortality together indicate that the development of effective therapeutics for IPF is an urgent need.In recent years,it was reported that DDRs are potential targets in anti-fibrosis treatment.Based on previous work we carried out further structure modifications and led to a more selective inhibitor 47 by averting some fibrosis-unrelated kinases,such as RET,AXL and ALK.Extensive profiling of compound 47 has demonstrated that it has potent DDR1/2 inhibitory activities,low toxicity,good pharmacokinetic properties and reliable in vivo anti-fibrosis efficacy.Therefore,we confirmed that discoidin domain receptors are promising drug targets for IPF,and compound 47 would be a promising candidate for further drug development.
基金supported by the National Natural Science Foundation of China (No. 12102470)the Hunan Provincial Innovation Foundation for Postgraduate (No. CX20200082), China。
文摘Unstart is an unwanted flow phenomenon in a hypersonic inlet. When an unstart occurs, the captured airflow flowing through the engine significantly decreases with strong unsteady characteristics, which may lead to thrust loss or even combustor flameout. In this study, various bump configurations were designed to be integrated with a hypersonic inlet to improve its starting ability. A bump was defined as an integrated 3D compression surface installed upstream of the inlet entrance. The starting processes of these bump inlets were numerically simulated to investigate the effect laws and flow mechanisms of the bump parameters. Tests on bump height revealed that the starting performance could be significantly improved by increasing bump height, with the starting Mach number decreasing by 0.55 for the inlet with the highest bump. The high bump facilitates the side movement of the subsonic flow in the separation zone, which leads to a small separation bubble, thus accelerating the starting process. Further, the starting ability can be improved by designing a relatively wide bump, which results in a decline in the starting Mach number by 0.44. When the bump has the same or greater width compared with the airflow capture range, a growing spillage along the transverse direction can be formed so that the airflow in the separation bubble can be easily excluded, improving the starting ability.