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Selective type II TRK inhibitors overcome xDFG mutation mediated acquired resistance to the second-generation inhibitors selitrectinib and repotrectinib

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Acta Pharmaceutica Sinica B 2024年第2期14卷 517-532页

作者： Shuang xiang Xiaoyun Lu International cooperative Laboratory of Traditional chinese Medicine Modernization and Innovative Drug Discovery of chinese Ministry of Education(MOE) Guangdong Provincial Key Laboratory of New Drug Design and EvaluationGuangzhou City Key Laboratory of Precision Chemical Drug DevelopmentSchool of PharmacyJinan UniversityGuangzhou 510632China

Neurotrophic receptor kinase(NTRK) fusions are actionable oncogenic drivers of multiple pediatric and adult solid tumors,and tropomyosin receptor kinase(TRK) has been considered as an attractive therapeutic target for "pan-cancer" harboring these ***,two generations TRK inhibitors have been *** representative second-generation inhibitors selitrectinib and repotrectinib were designed to overcome clinic acquired resistance of the first-generation inhibitors larotrectinib or entrectinib resulted from solvent-front and gatekeeper on-target ***,xDFG(TRKAG667c/A/S,homologous TRKcG696c/A/S) and some double mutations still confer resistance to selitrectinib and repotrectinib,and overcoming these resistances represents a major unmet clinical *** this review,we summarize the acquired resistance mechanism of the first-and second-generation TRK inhibitors,and firstly put forward the emerging selective type Ⅱ TRK inhibitors to overcome xDFG mutations mediated ***,we concluded our perspectives on new challenges and future directions in this field.

关键词： NTRK fusions TRK kinase clinical resistance xDFG mutations Selective type II inhibitors

On Hamiltonian Property of cayley Digraphs

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Acta Mathematicae Applicatae Sinica 2024年第2期40卷 547-556页

作者： Fang DUAN Qiong-xiang HUANG School of Mathematics Science Xinjiang Normal UniversityUrumqi 830017China college of Mathematics and Systems Science Xinjiang UniversityUrumqi 830017China

Let G be a finite group generated by S and c(G,S) the cayley digraphs of G with connection set *** this paper,we give some sufficient conditions for the existence of hamiltonian circuit in c(G,S),where G=Zm×H is a semiproduct of Zmby a subgroup H of *** particular,if m is a prime,then the cayley digraph of G has a hamiltonian circuit unless G=Zm×*** addition,we introduce a new digraph operation,called φ-semiproduct of Γ1by Γ2and denoted by Γ1×Γ_φΓ2,in terms of mapping φ:V(Γ2)→{1,-1}.Furthermore we prove that c(Zm,{a})×_φ c(H,S) is also a cayley digraph if φ is a homomorphism from H to{1,-1} ≤ Zm~*,which produces some classes of cayley digraphs that have hamiltonian circuits.

关键词： cayley digraphs hamiltonian circuit external semidirect product

Maximal operators of pseudo-differential operators with rough symbols

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Applied Mathematics(A Journal of chinese Universities) 2024年第1期39卷 174-180页

作者： Ramla Benhamoud ZHU xiang-rong School of Mathematical Sciences Zhejiang Normal UniversityJinhua 321004China

consider a pseudo-differential operator T_(a)f(x)=∫_(R^(n))e^(ix,ζ)a(x,ζ)f(ζ)dζwhere the symbol a is in the rough Hormander class L^(∞)S_(ρ)^(m)with m∈R andρ∈[0,1].In this note,when 1≤p≤2,if n(ρ-1)/p and a∈L^(∞)S_(ρ)^(m),then for any f∈S(R^(n))and x∈R^(n),we prove that M(T_(a)f)(x)≤c(M(|f|^(p))(x))^(1/p) where M is the Hardy-Littlewood maximal *** theorem improves the known results and the bound on m is sharp,in the sense that n(ρ-1)/p can not be replaced by a larger constant.

关键词： pseudo-differential operator rough Hormander class H-L maximal operator

Decomposition mechanisms of nuclear-grade cationic exchange resin by advanced oxidation processes:Statistical molecular fragmentation model and DFT calculations

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Journal of Environmental Sciences 2024年第1期135卷 433-448页

作者： xiang Meng Pierre Désesquelles Lejin Xu Department of Nuclear Engineering and Technology School of Energy and Power EngineeringHuazhong University of Science&TechnologyWuhan 430074China cNRS Laboratoire de Physique des Gaz et des PlasmasUniversitéParis-SaclayOrsay 91405France State Key Laboratory of coal combustion School of Energy and Power EngineeringHuazhong University of Science and TechnologyWuhan 430074China

The treatment and disposal of radioactive waste are presently facing great *** ion exchange resins have become a focus of attention due to their high production and serious environmental *** this paper,a simplified model of cationic exchange resin is proposed,and the degradation processes of cationic resin monomer initiated by hydroxyl radicals(·OH)are clarified by combining statistical molecular fragmentation(SMF)model and density functional theory(DFT)*** prediction of active sites indicates that the S-O bonds and the c-S bond of the sulfonic group are more likely to react during the *** meta-position of the sulfonic group on the benzene ring is the most active site,and the benzene ring without the sulfonic group has a certain *** c11-c14 and c17-c20 bonds,on the carbon skeleton,are the most easily *** is also found that dihydroxy addition and elimination reactions play a major role in the process of desulfonation,carbon skeleton cleavage and benzene ring *** decomposition mechanisms found through the combination of physical models and chemical calculations,provide theoretical guidance for the treatment of complex polycyclic aromatic hydrocarbons.

关键词： cationic exchange resin Statistical molecular fragmentation model Density functional theory Hydroxyl radical Decomposition mechanism

continuous Orbit Equivalence of Semigroup Actions

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Acta Mathematica Sinica,English Series 2024年第6期40卷 1581-1598页

作者： xiang Qi QIANG cheng Jun HOU School of Mathematical Science Yangzhou UniversityYangzhou 225002P.R.China

We introduce notions of continuous orbit equivalence and its one-sided version for countable left Ore semigroup actions on compact spaces by surjective local homeomorphisms,and characterize them in terms of the corresponding transformation groupoids and their operator *** particular,we show that two essentially free semigroup actions on totally disconnected compact spaces are continuously orbit equivalent if and only if there is a canonical abelian subalgebra preserving c^(∗)-isomorphism between the associated transformation groupoid c^(∗)-*** also give some examples of orbit equivalence,consider the special case of semigroup actions by homeomorphisms and relate continuous orbit equivalence of semigroup actions to that of the associated group actions.

关键词： Semigroup action continuous one-sided orbit equivalence continuous orbit equivalence groupoid c^(∗)-algebras

Attractor for the Extensible Beam Equation with Nonlocal Weak Damping on Time–Dependent Space

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Acta Mathematica Sinica,English Series 2024年第4期40卷 1115-1126页

作者： chun xiang ZHAO Feng Juan MENG Institute of Applied System Analysis Jiangsu UniversityZhenjiang 212013P.R.China School of Mathematics and Physics Jiangsu University of TechnologyChangzhou 213001P.R.China

In this article,we consider the long-time behavior of extensible beams with nonlocal weak damping:ε(t)u_(tt)+Δ^(2)u-m(‖▽u‖^(2))Δu+‖u_(t)‖^(p_(u_(t)))+f(u)=h,whereε(t)is a decreasing function vanishing at *** the theory of process on time-dependent spaces,we investigate the existence of the time-dependent attractor by using the condition(c_(t))method and more detailed *** results obtained essentially improve and complete some previous works.

关键词： Time-dependent attractor extensible beams equation nonlocal weak damping

Reynolds-number scaling analysis on lift generation of a flapping and passive rotating wing with an inhomogeneous mass distribution

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chinese Journal of Aeronautics 2024年第2期37卷 259-269页

作者： Suyang QIN Haotian HANG Yang xiang Hong LIU J.c.Wu center for aerodynamics school of aeronautics and astronauticsshanghai jiao tong universityshanghai 200240china

Insects usually fly by passively rotating wings,which has been applied to the design of flapping-wing Micro-Air Vehicles(MAVs)to reduce mechanical *** this paper,a robotic passive rotating-wing model is designed to investigate wing kinematics and lift generation,which are measured by a high-speed camera and a force transducer,*** addition,flow fields are measured using the Particle Image Velocimetry(PIV).Experimental results demonstrate that passive rotating motion has a coordinative relationship with actively stroking *** the stroke amplitude or frequency increases,the rotating amplitude is *** characterize the active stroking motion,a driving Reynolds number Redrivingis defined,which varies from 68 to 366 in this *** the gravity center of the wing towards trailing ed ge induces the increase of additional torque M,which decreases the wing rotating amplitude and promotes the advance of wing *** find that the timing of wing rotation is gradually delayed and the mean lift coefficient c^(-)_(L)monotonously decreases as *** increasing the additional torque M,c^(-)_(L)is slightly improved and approaches to the lift coefficient of a real fruit fly at driving Re approximately equal to *** instantaneous lifts combined with the vortical structures further demonstrate that the lift generation associated with wing rotation is mainly attributed to the growth of the LeadingEdge Vortex(LEV)and the passive wake capture *** wake capture is influenced by LEV,reversal stroke motion and wing additional torque together,which can only maintain the lift at a high level for a considerable *** high-lift generation mechanisms of flapping and passive rotating flight could shed light on the simplified design of MAVs and the improvement of their aerodynamic performance.

关键词： Flapping flight Unsteady lift Passive rotation Vortex flow Leading-edge vortex

Precipitating thermally reinforcement phase in aluminum alloys for enhanced strength at 400℃

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Journal of Materials Science & Technology 2024年第5期172卷 71-82页

作者： xiang Su Yuan Lei Yang chen Hongjie Qu Zhixiang Qi Gong Zheng Xu Liu Henggao xiang Guang chen National Key Laboratory of Advanced casting Technologies MIIT Key Laboratory of Advanced Metallic and Intermetallic Materials TechnologyEngineering Research Center of Materials Behavior and DesignMinistry of EducationNanjing University of Science and TechnologyNanjing 210094China School of Aviation and Mechanical Engineering Changzhou Institute of TechnologyChangzhou 213032China

Heat-resistant aluminum alloys are widely used in aerospace and automotive fields for manufacturing hot components due to their advantages in lightweight design and energy ***,the high-temperature strength of existing cast aluminum alloys is always limited to about 100 MPa at 350℃due to coarsening and transformation of strengthening ***,we reveal that the yield strength and ultimate tensile strength of the T6 state Al-8.4cu-2.3ce-1.0Mn-0.5Ni-0.2Zr alloy at 400◦c increase by 34%and 44%after re-aging at 300℃for 100 h,and its thermal strength exhibits distinguished ad-vantage over traditional heat-resistant aluminum *** enhanced elevated-temperature strength is attributed to the reprecipitation of the Ni-bearing T-Al_(20)cu_(2)Mn_(3)phase,whose number density increases over one *** significant segregation of Ni,ce,and Zr elements at the interfaces helps improve the thermal stability of the T *** thermostable T phase effectively strengthens the matrix by in-hibiting dislocation ***,a highly interconnected 3D intermetallic network along the grain boundaries can still remain after long-term re-aging at 300℃,which is conducive to imposing a drag on the grain boundaries at high *** finding offers a viable route for enhancing the elevated-temperature strength of heat-resistant aluminum alloys,which could provide expanded opportunities for higher-temperature applications.

关键词： Aluminum alloys Precipitation Thermally reinforcement phase Re-aging treatment High-temperature strength

Flexible electrochemical capacitor based NiMoSSe electrode material with superior cycling and structural stability

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chinese chemical Letters 2024年第7期35卷 456-460页

作者： Jingxuan Liu Shiqi Zhao xiang Wu School of Materials Science and Engineering Shenyang University of TechnologyShenyang 110870China

constructing composited electrode material is considered to be an efficient strategy to improve their electrochemical *** can accelerate the charge transfer speed of ions and enhance the conductivity of ***,the formation of the hybrid structure can largely avoid the aggregation of two dimensional materials and increase the electrochemical active area of the *** this work,we synthesize NiMoSSe electrode materials on nickel foam by a facile hydrothermal *** prepared composite shows a specific capacitance of 1035 c/g at 1 A/g due to the synergistic effect between MoS_(2) and MoSe_(2) *** addition,the devices are assembled with NiMoSSe samples,which offers an energy density of 82.71 Wh/kg at a power density of 2700 W/kg.

关键词： Supercapacitors NiMoSSe Energy density Power density cycling life