The effectiveness of mobile robot aided for architectural construction depends strongly on its accurate localization ability.Localization of mobile robot is increasingly important for the printing of buildings in the ...The effectiveness of mobile robot aided for architectural construction depends strongly on its accurate localization ability.Localization of mobile robot is increasingly important for the printing of buildings in the construction scene.Although many available studies on the localization have been conducted,only a few studies have addressed the more challenging problem of localization for mobile robot in large-scale ongoing and featureless scenes.To realize the accurate localization of mobile robot in designated stations,we build an artificial landmark map and propose a novel nonlinear optimization algorithm based on graphs to reduce the uncertainty of the whole map.Then,the performances of localization for mobile robot based on the original and optimized map are compared and evaluated.Finally,experimental results show that the average absolute localization errors that adopted the proposed algorithm is reduced by about 21%compared to that of the original map.展开更多
Gabapentinoid drugs(pregabalin and gabapentin) have been successfully used in the treatment of neuro pathic pain and in focal seizure prevention.Recent research has demonstrated their potent activities in modulating n...Gabapentinoid drugs(pregabalin and gabapentin) have been successfully used in the treatment of neuro pathic pain and in focal seizure prevention.Recent research has demonstrated their potent activities in modulating neurotransmitter release in neuronal tissue,oxidative stress,and inflammation,which matches the mechanism of action via voltage-gated calcium channels.In this review,we briefly elaborate on the medicinal history and ligand-binding sites of gabapentinoids.We systematically summarize the preclinical and clinical research on gabapentinoids in stroke,including ischemic stro ke,intracerebral hemorrhage,subarachnoid hemorrhage,seizures after stro ke,cortical spreading depolarization after stroke,pain after stroke,and nerve regeneration after stro ke.This review also discusses the potential to rgets of gabapentinoids in stroke;however,the existing results are still unce rtain regarding the effect of gabapentinoids on stroke and related diseases.Further preclinical and clinical trials are needed to test the therapeutic potential of gabapentinoids in stroke.Therefore,gabapentinoids have both opportunities and challenges in the treatment of stroke.展开更多
The establishment of efficient oxygen evolution electrocatalysts is of great value but also challenging.Herein,a durable metal–organic framework(MOF)with minor atomically dispersed ruthenium and an optimized electron...The establishment of efficient oxygen evolution electrocatalysts is of great value but also challenging.Herein,a durable metal–organic framework(MOF)with minor atomically dispersed ruthenium and an optimized electronic structure is constructed as an efficient electrocatalyst.Significantly,the obtained NiRu_(0.08)-MOF with doping Ru only needs an overpotential of 187 mV at 10 mA cm^(-2) with a Tafel slop of 40 mV dec^(-1) in 0.1M KOH for the oxygen evolution reaction,and can work continuously for more than 300 h.Ultrahigh Ru mass activity is achieved,reaching 56.7 Ag^(-1)_(Ru) at an overpotential of 200 mV,which is 36 times higher than that of commercial RuO_(2).X-ray adsorption spectroscopy and density function theory calculations reveal that atomically dispersed ruthenium on metal sites in MOFs is expected to optimize the electronic structure of nickel sites,thus improving the conductivity of the catalyst and optimizing the adsorption energy of intermediates,resulting in significant optimization of electrocatalytic performance.This study could provide a new avenue for the design of efficient and stable MOF electrocatalysts.展开更多
Multiple Automatic Guided Vehicle(multi-AGVs)management systems provide an effective solution to ensuring stable operations of multi-AGVs in the same scenario,such as flexible manufacturing systems,warehouses,containe...Multiple Automatic Guided Vehicle(multi-AGVs)management systems provide an effective solution to ensuring stable operations of multi-AGVs in the same scenario,such as flexible manufacturing systems,warehouses,container terminals,etc.This type of systems need to balance the relationship among the resources of the system and solve the problems existing in the operation to make the system in line with the requirement of the administrator.The multi-AGVs management problem is a multi-objective,multi-constraint combinatorial optimization problem,which depends on the types of application scenarios.This article classifies and compares the research papers on multi-AGVs management in detail.Firstly,according to the different dimensions of the problem,the multi-AGVs management system is analyzed from three perspectives,namely,1)task dimensiondispatch,2)spatial dimension-path,and 3)time dimension-scheduling.The detailed comparison between the three dimensions and their respective solutions are discussed in detail as well.Secondly,according to their utility,the multi-AGVs management problems are divided into three categories:1)cost reduction,resource-oriented,2)efficiency improvement,problem-oriented,3)personalized demand,goal-oriented.The algorithm and methods of the different utility-oriented are analyzed and discussed.The related literature is summarized and corresponds to the composition of the multi-AGVs management system and the multi-AGVs management problems.Finally,according to the literature review,suggestions are made for further research.展开更多
Building a community with a shared future for mankind calls for contemporary Chinese people’s understanding of the future of the community of mankind.Chinese people must also be encouraged to engage in the practices ...Building a community with a shared future for mankind calls for contemporary Chinese people’s understanding of the future of the community of mankind.Chinese people must also be encouraged to engage in the practices of global governance.Given their historical traditions,cultura thoughts and our nation’s current conditions,contemporary Chinese people must enhance their understanding of the development of the modern world especially the intertwined fate and differentiated interests of humans within such a community.Chinese people must arm themselves with a better globa view,cultivate a global consciousness,consolidate the concept of community and participate with a more open view,a more inclusive mind and more sensible strategies in the campaign initiated by the CPC to build an open inclusive,clean,and beautiful world that enjoys lasting peace,universa security,and common prosperity.Grand-scale education must be launched and relevant policy must be introduced to enhance people’s enthusiasm for global governance.International cooperation and communications mus be expanded so that Chinese people’s awareness of the community can be strengthened.Then a community with a shared future for mankind tha follows the rules of the development of China and the world,and that respects the historical trends and serves multiple interests can be constructed.展开更多
Rheumatoid arthritis(RA)is a common chronic inflammatory disorder that usually affects joints.It was found that roburic acid(RBA),an ingredient from anti-RA herb Gentiana macrophylla Pall.,displayed strong anti-inflam...Rheumatoid arthritis(RA)is a common chronic inflammatory disorder that usually affects joints.It was found that roburic acid(RBA),an ingredient from anti-RA herb Gentiana macrophylla Pall.,displayed strong anti-inflammatory activity.However,its medical application is limited by its hydrophobicity,lack of targeting capability and unclear functional mechanism.Here,we constructed a pH responsive dual-target drug delivery system hitchhiking RBA(RBA-NPs)that targeted both CD44 and folate receptors,and investigated its pharmacological mechanism.In rat RA model,the nanocarriers effectively delivered RBA to inflammatory sites and significantly enhanced the therapeutic outcomes compared with free RBA,as well as strongly reducing inflammatory cytokine levels and promoting tissue repair.Following analysis revealed that M1 macrophages in the joints were reprogrammed to M2 phenotype by RBA.Since the balance of pro-and anti-inflammatory macrophages play important roles in maintaining immune homeostasis and preventing excessive inflammation in RA,this reprogramming is likely responsible for the anti-RA effect.Furthermore,we revealed that RBA-NPs drove M1-to-M2 phenotypic switch by down-regulating the glycolysis level via blocking ERK/HIF-1α/GLUT1 pathway.Thus,our work not only developed a targeting delivery system that remarkably improved the anti-RA efficiency of RBA,but also identified a potential molecular target to reversely reprogram macrophages though energy metabolism regulation.展开更多
Background:Abnormal alternative splicing is frequently associated with carcinogenesis.In B-cell acute lymphoblastic leukemia(B-ALL),double homeobox 4 fused with immunoglobulin heavy chain(DUX4/IGH)can lead to the aber...Background:Abnormal alternative splicing is frequently associated with carcinogenesis.In B-cell acute lymphoblastic leukemia(B-ALL),double homeobox 4 fused with immunoglobulin heavy chain(DUX4/IGH)can lead to the aberrant production of E-26 transformation-specific family related gene abnormal transcript(ERGalt)and other splicing variants.However,the molecular mechanism underpinning this process remains elusive.Here,we aimed to know how DUX4/IGH triggers abnormal splicing in leukemia.Methods:The differential intron retention analysis was conducted to identify novel DUX4/IGH-driven splicing in B-ALL patients.X-ray crystallography,small angle X-ray scattering(SAXS),and analytical ultracentrifugation were used to investigate how DUX4/IGH recognize double DUX4 responsive element(DRE)-DRE sites.The ERGalt biogenesis and B-cell differentiation assays were performed to characterize the DUX4/IGH crosslinking activity.To check whether recombination-activating gene 1/2(RAG1/2)was required for DUX4/IGH-driven splicing,the proximity ligation assay,co-immunoprecipitation,mammalian two hybrid characterizations,in vitro RAG1/2 cleavage,and shRNA knock-down assays were performed.Results:We reported previously unrecognized intron retention events in Ctype lectin domain family 12,member A abnormal transcript(CLEC12Aalt)and chromosome 6 open reading frame 89 abnormal transcript(C6orf89alt),where also harbored repetitive DRE-DRE sites.Supportively,X-ray crystallography and SAXS characterization revealed that DUX4 homeobox domain(HD)1-HD2 might dimerize into a dumbbell-shape trans configuration to crosslink two adjacent DRE sites.Impaired DUX4/IGH-mediated crosslinking abolishes ERGalt,CLEC12Aalt,and C6orf89alt biogenesis,resulting in marked alleviation of its inhibitory effect on B-cell differentiation.Furthermore,we also observed a rare RAG1/2-mediated recombination signal sequence-like DNA edition in DUX4/IGH target genes.Supportively,shRNA knock-down of RAG1/2 in leukemic Reh cells consistently impaired the biogenesis of ERGalt,CLEC12Aalt,and C6orf89alt.Conclusions:All these results suggest that DUX4/IGH-driven DNA crosslinking is required for RAG1/2 recruitment onto the double tandem DRE-DRE sites,catalyzing V(D)J-like recombination and oncogenic splicing in acute lymphoblastic leukemia.展开更多
Carbon-based nanomaterials,including carbon nanotubes,carbon nanospheres,and carbon nanofibers,are becoming a research hotspot due to their unique structure and good mechanical,thermal,electrical,optical,and chemical ...Carbon-based nanomaterials,including carbon nanotubes,carbon nanospheres,and carbon nanofibers,are becoming a research hotspot due to their unique structure and good mechanical,thermal,electrical,optical,and chemical properties.With the development of material synthesis technology,they can be functionalized and used in various fields such as energy,environment,and biomedicine.In particular,stimuli-responsive carbon-based nanomaterials have stood out in recent years because of their smart behavior.Researchers have applied carbon-based nanomaterials to different disease treatments based on their stimulus-response properties.In this paper,based on stimuli-responsive carbon-based nanomaterials’morphology,we categorize them into carbon nanotubes,carbon nanospheres,and carbon nanofibers according to their morphology.Then,their applications in probes,bioimaging,tumor therapy,and other fields are discussed.Finally,we address the advantages and disadvantages of carbon-based stimuliresponsive nanomaterials and discuss their future perspective.展开更多
Identification of epitopes targeted following virus infection or vaccination can guide vaccine design and development of therapeutic interventions targeting functional sites,but can be laborious.Herein,we employed pep...Identification of epitopes targeted following virus infection or vaccination can guide vaccine design and development of therapeutic interventions targeting functional sites,but can be laborious.Herein,we employed peptide microarrays to map linear peptide epitopes(LPEs)recognized following SARS-CoV-2 infetion and vaccination.LPEs detected by nonhuman primate(NHP)and patient IgMs after SARS-CoV-2 infection extensively overlapped,localized to functionally important virus regions,and aligned with reported neutralizing antibody binding sies.Similar LPE overlap occurred atfter infection and vaccination,with LPE clusters specifc to each stimulus,where strong and conserved LPEs mapping to sites known or likely to inhibit spike protein function.Vaccine-specifc LPEs tended to map to sites known or likely to be afected by structural changes induced by the proline substitutions in the mRNA vaccine's S protein.Mapping LPEs to regions of known functional importance in this manner may acelerate vaccine evaluation and discovery of targets for sile secific therapeutic interventions.展开更多
Finite Element Exterior Calculus (FEEC) was developed by Arnold, Falk, Winther andothers over the last decade to exploit the observation that mixed variational problems canbe posed on a Hilbert complex, and Galerkin-t...Finite Element Exterior Calculus (FEEC) was developed by Arnold, Falk, Winther andothers over the last decade to exploit the observation that mixed variational problems canbe posed on a Hilbert complex, and Galerkin-type mixed methods can then be obtained bysolving finite-dimensional subcomplex problems. Chen, Holst, and Xu (Math. Comp. 78(2009) 35–53) established convergence and optimality of an adaptive mixed finite elementmethod using Raviart–Thomas or Brezzi–Douglas–Marini elements for Poisson’s equationon contractible domains in R^2, which can be viewed as a boundary problem on the deRham complex. Recently Demlow and Hirani (Found. Math. Comput. 14 (2014) 1337–1371) developed fundamental tools for a posteriori analysis on the de Rham complex.In this paper, we use tools in FEEC to construct convergence and complexity resultson domains with general topology and spatial dimension. In particular, we construct areliable and efficient error estimator and a sharper quasi-orthogonality result using a noveltechnique. Without marking for data oscillation, our adaptive method is a contractionwith respect to a total error incorporating the error estimator and data oscillation.展开更多
PML nuclear bodies(NBs),which are increasingly recognized as the central hub of many cellular signaling events,are superassembled spherical complexes with diameters of 0.1–2mm.Recent studies reveal that RING tetramer...PML nuclear bodies(NBs),which are increasingly recognized as the central hub of many cellular signaling events,are superassembled spherical complexes with diameters of 0.1–2mm.Recent studies reveal that RING tetramerization and B1-box polymerization are key factors to the overall PML NBs assembly.The productive RBCC oligomerization allows subsequent PML biogenesis steps,including the PML auto-sumoylation and partners recruitment via SUMO–SIM interactions.In promyelocytic leukemia,the oncoprotein PML/RARa(P/R)inhibits PML NBs assembly and leads to a full-fledged leukemogenesis.In this review,we review the recent progress in PML and acute promyelocytic leukemia fields,highlighting the protein oligomerization as an important direction of future targeted therapy.展开更多
Lightweight design is important for the Thermal Protection System(TPS) of hypersonic vehicles in that it protects the inner structure from severe heating environment. However, due to the existence of uncertainties in ...Lightweight design is important for the Thermal Protection System(TPS) of hypersonic vehicles in that it protects the inner structure from severe heating environment. However, due to the existence of uncertainties in material properties and geometry, it is imperative to incorporate uncertainty analysis into the design optimization to obtain reliable results. In this paper, a six sigma robust design optimization based on Successive Response Surface Method(SRSM) is established for the TPS to improve the reliability and robustness with considering the uncertainties. The uncertain parameters related to material properties and thicknesses of insulation layers are considered and characterized by random variables following normal distributions. By employing SRSM, the values of objective function and constraints are approximated by the response surfaces to reduce computational cost. The optimization is an iterative process with response surfaces updating to find the true optimal solution. The optimization of the nose cone of hypersonic vehicle cabin is provided as an example to illustrate the feasibility and effectiveness of the proposed method.展开更多
基金This research was supported by National Natural Science Foundation of China(Nos.U1913603,61803251,51775322)National Key Research and Development Program of China(No.2019YFB1310003).
文摘The effectiveness of mobile robot aided for architectural construction depends strongly on its accurate localization ability.Localization of mobile robot is increasingly important for the printing of buildings in the construction scene.Although many available studies on the localization have been conducted,only a few studies have addressed the more challenging problem of localization for mobile robot in large-scale ongoing and featureless scenes.To realize the accurate localization of mobile robot in designated stations,we build an artificial landmark map and propose a novel nonlinear optimization algorithm based on graphs to reduce the uncertainty of the whole map.Then,the performances of localization for mobile robot based on the original and optimized map are compared and evaluated.Finally,experimental results show that the average absolute localization errors that adopted the proposed algorithm is reduced by about 21%compared to that of the original map.
基金supported by the National Key R&D Program of China,No.2020YFC2008302the National Natural Science Foundation of China,No.81673631the Science and Technology Program of Sichuan Province,No.2020YFH0059 (all to YL)。
文摘Gabapentinoid drugs(pregabalin and gabapentin) have been successfully used in the treatment of neuro pathic pain and in focal seizure prevention.Recent research has demonstrated their potent activities in modulating neurotransmitter release in neuronal tissue,oxidative stress,and inflammation,which matches the mechanism of action via voltage-gated calcium channels.In this review,we briefly elaborate on the medicinal history and ligand-binding sites of gabapentinoids.We systematically summarize the preclinical and clinical research on gabapentinoids in stroke,including ischemic stro ke,intracerebral hemorrhage,subarachnoid hemorrhage,seizures after stro ke,cortical spreading depolarization after stroke,pain after stroke,and nerve regeneration after stro ke.This review also discusses the potential to rgets of gabapentinoids in stroke;however,the existing results are still unce rtain regarding the effect of gabapentinoids on stroke and related diseases.Further preclinical and clinical trials are needed to test the therapeutic potential of gabapentinoids in stroke.Therefore,gabapentinoids have both opportunities and challenges in the treatment of stroke.
基金National Natural Science Foundation of China,Grant/Award Number:51632008。
文摘The establishment of efficient oxygen evolution electrocatalysts is of great value but also challenging.Herein,a durable metal–organic framework(MOF)with minor atomically dispersed ruthenium and an optimized electronic structure is constructed as an efficient electrocatalyst.Significantly,the obtained NiRu_(0.08)-MOF with doping Ru only needs an overpotential of 187 mV at 10 mA cm^(-2) with a Tafel slop of 40 mV dec^(-1) in 0.1M KOH for the oxygen evolution reaction,and can work continuously for more than 300 h.Ultrahigh Ru mass activity is achieved,reaching 56.7 Ag^(-1)_(Ru) at an overpotential of 200 mV,which is 36 times higher than that of commercial RuO_(2).X-ray adsorption spectroscopy and density function theory calculations reveal that atomically dispersed ruthenium on metal sites in MOFs is expected to optimize the electronic structure of nickel sites,thus improving the conductivity of the catalyst and optimizing the adsorption energy of intermediates,resulting in significant optimization of electrocatalytic performance.This study could provide a new avenue for the design of efficient and stable MOF electrocatalysts.
基金funded by the National Key Research and Development Program of China(No.2019YFB1310003)by the National Natural Science Foundation of China(Nos.U1913603,61803251 and 51775322)funded by the Shanghai Collaborative Innovation Center of Intelligent Manufacturing Robot Technology for Large Components(No.ZXZ20211101).
文摘Multiple Automatic Guided Vehicle(multi-AGVs)management systems provide an effective solution to ensuring stable operations of multi-AGVs in the same scenario,such as flexible manufacturing systems,warehouses,container terminals,etc.This type of systems need to balance the relationship among the resources of the system and solve the problems existing in the operation to make the system in line with the requirement of the administrator.The multi-AGVs management problem is a multi-objective,multi-constraint combinatorial optimization problem,which depends on the types of application scenarios.This article classifies and compares the research papers on multi-AGVs management in detail.Firstly,according to the different dimensions of the problem,the multi-AGVs management system is analyzed from three perspectives,namely,1)task dimensiondispatch,2)spatial dimension-path,and 3)time dimension-scheduling.The detailed comparison between the three dimensions and their respective solutions are discussed in detail as well.Secondly,according to their utility,the multi-AGVs management problems are divided into three categories:1)cost reduction,resource-oriented,2)efficiency improvement,problem-oriented,3)personalized demand,goal-oriented.The algorithm and methods of the different utility-oriented are analyzed and discussed.The related literature is summarized and corresponds to the composition of the multi-AGVs management system and the multi-AGVs management problems.Finally,according to the literature review,suggestions are made for further research.
基金A Study on the Ideological and Political Situation of Young Teachers and Students in Colleges andUniversities"(2015MZD107)a major project of the research and construction of Marxist theory led by Publicity Department,CPC Central Committee+1 种基金"The Disciplinary Construction of Marxism in Colleges and Universities and the Teaching Reform ofIdeological and Political Courses"(16JJD710003)a major project of the key research base of humanities and social sciences,theMinistry of Education of PRC,2016
文摘Building a community with a shared future for mankind calls for contemporary Chinese people’s understanding of the future of the community of mankind.Chinese people must also be encouraged to engage in the practices of global governance.Given their historical traditions,cultura thoughts and our nation’s current conditions,contemporary Chinese people must enhance their understanding of the development of the modern world especially the intertwined fate and differentiated interests of humans within such a community.Chinese people must arm themselves with a better globa view,cultivate a global consciousness,consolidate the concept of community and participate with a more open view,a more inclusive mind and more sensible strategies in the campaign initiated by the CPC to build an open inclusive,clean,and beautiful world that enjoys lasting peace,universa security,and common prosperity.Grand-scale education must be launched and relevant policy must be introduced to enhance people’s enthusiasm for global governance.International cooperation and communications mus be expanded so that Chinese people’s awareness of the community can be strengthened.Then a community with a shared future for mankind tha follows the rules of the development of China and the world,and that respects the historical trends and serves multiple interests can be constructed.
基金This work was supported by the National Science Fund for Excellent Young Scholars(No:82022070)the Regional Innovation and Development Joint Fund(No:U20A20411).
文摘Rheumatoid arthritis(RA)is a common chronic inflammatory disorder that usually affects joints.It was found that roburic acid(RBA),an ingredient from anti-RA herb Gentiana macrophylla Pall.,displayed strong anti-inflammatory activity.However,its medical application is limited by its hydrophobicity,lack of targeting capability and unclear functional mechanism.Here,we constructed a pH responsive dual-target drug delivery system hitchhiking RBA(RBA-NPs)that targeted both CD44 and folate receptors,and investigated its pharmacological mechanism.In rat RA model,the nanocarriers effectively delivered RBA to inflammatory sites and significantly enhanced the therapeutic outcomes compared with free RBA,as well as strongly reducing inflammatory cytokine levels and promoting tissue repair.Following analysis revealed that M1 macrophages in the joints were reprogrammed to M2 phenotype by RBA.Since the balance of pro-and anti-inflammatory macrophages play important roles in maintaining immune homeostasis and preventing excessive inflammation in RA,this reprogramming is likely responsible for the anti-RA effect.Furthermore,we revealed that RBA-NPs drove M1-to-M2 phenotypic switch by down-regulating the glycolysis level via blocking ERK/HIF-1α/GLUT1 pathway.Thus,our work not only developed a targeting delivery system that remarkably improved the anti-RA efficiency of RBA,but also identified a potential molecular target to reversely reprogram macrophages though energy metabolism regulation.
基金National Natural Science Foundation of China,Grant/Award Numbers:81970132,81770142,81800144,31800642Shanghai Science and Technology Committee,Grant/Award Number:20JC1410600+3 种基金Shanghai Guangci Translational Medical Research Development FoundationShanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support,Grant/Award Number:20152504The Program for Professor of Special Appointment(Eastern Scholar)at Shanghai Institute of Higher LearningSamuel Waxman Cancer Research Foundation。
文摘Background:Abnormal alternative splicing is frequently associated with carcinogenesis.In B-cell acute lymphoblastic leukemia(B-ALL),double homeobox 4 fused with immunoglobulin heavy chain(DUX4/IGH)can lead to the aberrant production of E-26 transformation-specific family related gene abnormal transcript(ERGalt)and other splicing variants.However,the molecular mechanism underpinning this process remains elusive.Here,we aimed to know how DUX4/IGH triggers abnormal splicing in leukemia.Methods:The differential intron retention analysis was conducted to identify novel DUX4/IGH-driven splicing in B-ALL patients.X-ray crystallography,small angle X-ray scattering(SAXS),and analytical ultracentrifugation were used to investigate how DUX4/IGH recognize double DUX4 responsive element(DRE)-DRE sites.The ERGalt biogenesis and B-cell differentiation assays were performed to characterize the DUX4/IGH crosslinking activity.To check whether recombination-activating gene 1/2(RAG1/2)was required for DUX4/IGH-driven splicing,the proximity ligation assay,co-immunoprecipitation,mammalian two hybrid characterizations,in vitro RAG1/2 cleavage,and shRNA knock-down assays were performed.Results:We reported previously unrecognized intron retention events in Ctype lectin domain family 12,member A abnormal transcript(CLEC12Aalt)and chromosome 6 open reading frame 89 abnormal transcript(C6orf89alt),where also harbored repetitive DRE-DRE sites.Supportively,X-ray crystallography and SAXS characterization revealed that DUX4 homeobox domain(HD)1-HD2 might dimerize into a dumbbell-shape trans configuration to crosslink two adjacent DRE sites.Impaired DUX4/IGH-mediated crosslinking abolishes ERGalt,CLEC12Aalt,and C6orf89alt biogenesis,resulting in marked alleviation of its inhibitory effect on B-cell differentiation.Furthermore,we also observed a rare RAG1/2-mediated recombination signal sequence-like DNA edition in DUX4/IGH target genes.Supportively,shRNA knock-down of RAG1/2 in leukemic Reh cells consistently impaired the biogenesis of ERGalt,CLEC12Aalt,and C6orf89alt.Conclusions:All these results suggest that DUX4/IGH-driven DNA crosslinking is required for RAG1/2 recruitment onto the double tandem DRE-DRE sites,catalyzing V(D)J-like recombination and oncogenic splicing in acute lymphoblastic leukemia.
基金the National Natural Science Foundation of China(32101153).
文摘Carbon-based nanomaterials,including carbon nanotubes,carbon nanospheres,and carbon nanofibers,are becoming a research hotspot due to their unique structure and good mechanical,thermal,electrical,optical,and chemical properties.With the development of material synthesis technology,they can be functionalized and used in various fields such as energy,environment,and biomedicine.In particular,stimuli-responsive carbon-based nanomaterials have stood out in recent years because of their smart behavior.Researchers have applied carbon-based nanomaterials to different disease treatments based on their stimulus-response properties.In this paper,based on stimuli-responsive carbon-based nanomaterials’morphology,we categorize them into carbon nanotubes,carbon nanospheres,and carbon nanofibers according to their morphology.Then,their applications in probes,bioimaging,tumor therapy,and other fields are discussed.Finally,we address the advantages and disadvantages of carbon-based stimuliresponsive nanomaterials and discuss their future perspective.
基金supported by the Department of Defense(grant number W8IxwH19i0926)National Institute of Allergy and Infectious Diseases contract(grant number_HHSN2722017000331)+1 种基金National Institute of Child Health and Human Development grant(grant numbers R01HD090927 and R01HDi03511)National Center for Research Resources and the Ofice of Research Infrastructure Programs(grant numbers OD011104).
文摘Identification of epitopes targeted following virus infection or vaccination can guide vaccine design and development of therapeutic interventions targeting functional sites,but can be laborious.Herein,we employed peptide microarrays to map linear peptide epitopes(LPEs)recognized following SARS-CoV-2 infetion and vaccination.LPEs detected by nonhuman primate(NHP)and patient IgMs after SARS-CoV-2 infection extensively overlapped,localized to functionally important virus regions,and aligned with reported neutralizing antibody binding sies.Similar LPE overlap occurred atfter infection and vaccination,with LPE clusters specifc to each stimulus,where strong and conserved LPEs mapping to sites known or likely to inhibit spike protein function.Vaccine-specifc LPEs tended to map to sites known or likely to be afected by structural changes induced by the proline substitutions in the mRNA vaccine's S protein.Mapping LPEs to regions of known functional importance in this manner may acelerate vaccine evaluation and discovery of targets for sile secific therapeutic interventions.
基金MS was partially supported by NSF Awards 1620366,1262982,and 1217175.YL was partially supported by NSF Award 1620366.AM adn RS were partially supported by NSF Award 1217175.
文摘Finite Element Exterior Calculus (FEEC) was developed by Arnold, Falk, Winther andothers over the last decade to exploit the observation that mixed variational problems canbe posed on a Hilbert complex, and Galerkin-type mixed methods can then be obtained bysolving finite-dimensional subcomplex problems. Chen, Holst, and Xu (Math. Comp. 78(2009) 35–53) established convergence and optimality of an adaptive mixed finite elementmethod using Raviart–Thomas or Brezzi–Douglas–Marini elements for Poisson’s equationon contractible domains in R^2, which can be viewed as a boundary problem on the deRham complex. Recently Demlow and Hirani (Found. Math. Comput. 14 (2014) 1337–1371) developed fundamental tools for a posteriori analysis on the de Rham complex.In this paper, we use tools in FEEC to construct convergence and complexity resultson domains with general topology and spatial dimension. In particular, we construct areliable and efficient error estimator and a sharper quasi-orthogonality result using a noveltechnique. Without marking for data oscillation, our adaptive method is a contractionwith respect to a total error incorporating the error estimator and data oscillation.
基金supported by research grants 81970132,81770142,81370620,81570120,31070645,81800144,and 31800642 from National Natural Science Foundation of Chinaa research grant 20152504 from Shanghai Municipal Education Commission—Gaofeng Clinical Medicine Grant Support+4 种基金The Program for Professor of Special Appointment(Eastern Scholar)at Shanghai Institute of Higher Learninga research grant 11JC1407200 from SMSTCa research grant 12ZZ109 from SMEProgram for New Century Excellent Talents in University(NCET-10–9571)Samuel Waxman Cancer Research Foundation.
文摘PML nuclear bodies(NBs),which are increasingly recognized as the central hub of many cellular signaling events,are superassembled spherical complexes with diameters of 0.1–2mm.Recent studies reveal that RING tetramerization and B1-box polymerization are key factors to the overall PML NBs assembly.The productive RBCC oligomerization allows subsequent PML biogenesis steps,including the PML auto-sumoylation and partners recruitment via SUMO–SIM interactions.In promyelocytic leukemia,the oncoprotein PML/RARa(P/R)inhibits PML NBs assembly and leads to a full-fledged leukemogenesis.In this review,we review the recent progress in PML and acute promyelocytic leukemia fields,highlighting the protein oligomerization as an important direction of future targeted therapy.
基金supported by the National Key Research and Development Program of China (No. 2016YFB0200700)the National Nature Science Foundation of China (No. 11872089, No. 11572024, No. 11432002)Defence Industrial Technology Development Programs of China (No. JCKY2016601B001, No. JCKY2016204B101, No. JCKY2017601B001) for the financial supports
文摘Lightweight design is important for the Thermal Protection System(TPS) of hypersonic vehicles in that it protects the inner structure from severe heating environment. However, due to the existence of uncertainties in material properties and geometry, it is imperative to incorporate uncertainty analysis into the design optimization to obtain reliable results. In this paper, a six sigma robust design optimization based on Successive Response Surface Method(SRSM) is established for the TPS to improve the reliability and robustness with considering the uncertainties. The uncertain parameters related to material properties and thicknesses of insulation layers are considered and characterized by random variables following normal distributions. By employing SRSM, the values of objective function and constraints are approximated by the response surfaces to reduce computational cost. The optimization is an iterative process with response surfaces updating to find the true optimal solution. The optimization of the nose cone of hypersonic vehicle cabin is provided as an example to illustrate the feasibility and effectiveness of the proposed method.