RESUMO
To study the perforation performance of CFRP laminates for rail vehicles under high-velocity impact from foreign objects, impact tests on CFRP laminates at a velocity of 163 m/s were carried out, and a corresponding finite element model was established using ABAQUS and verified. The user-defined material subroutine combined the material strain rate hardening effect and the 3D-Hashin damage criterion. The effects of impact velocity, impact object shape, and oblique angle on the perforation performance of CFRP laminates are discussed. Results show that impact velocity positively correlates with impact peak force and residual velocity. Laminates can be perforated by projectiles with a velocity above 120 m/s, and impact velocity greatly influences delamination below 140 m/s. Three shapes of projectile impacting laminates are considered: spherical, cylindrical, and conical. The conical projectile penetrates the laminate most easily, with the largest delamination area. The cylindrical projectile with a flat end suffers the most resistance, and the delaminated area is between the impact conditions of the conical and spherical projectiles. Increasing the angle of inclination increases the impacted area of the laminate and the extent of damage, thus dissipating more energy. The projectile fails to penetrate the laminate when the oblique angle reaches 60°. CFRP composite structures penetrated by high-speed impacts pose a significant threat to the safety of train operations, providing an opportunity for the application of bio-inspired composite structures.
RESUMO
In this study, a series of 2-[p-fluorophenyl]-6-substituted-9H-purine analogues were designed and synthesized as CHK1 inhibitors, among which compound b22 was the most potent. b22 exhibited nearly no antiproliferative activity toward HT29 cells and displayed a significant antitumor potentiating effect on HT29 cells when treated in combination with gemcitabine (Gem). A time-dependent assay found that treatment with Gem for 8 h before adding b22 achieved the optimal effect. Furthermore, the immunofluorescence and qPCR results demonstrated that b22 can remarkably reverse the upregulation of PD-L1 induced by Gem, which suggested dual effects of b22 in antitumor potentiation and antitumor immunity.
Assuntos
Antígeno B7-H1 , Gencitabina , Humanos , Regulação para Baixo , Células HT29 , Purinas/farmacologia , Linhagem Celular TumoralRESUMO
In this study, a series of 2-substituted thieno[3,2-d]pyrimidin-4-yl(3,4,5-trimethoxyphenyl)methanones were designed, synthesized and evaluated as novel anti-tubulin polymerization and vascular disrupting agents. A pyrrolidin-1-yl derivative, compound 20, exhibited strong antiproliferative activities (average IC50 = 13.4 nM) against four cancer cell lines. 20 also showed retained potency toward paclitaxel-resistant A549 cells. 20 could significantly inhibit tubulin polymerization with an IC50 of 1.6 µM. 20 displayed strong induction of G2/M arrest and apoptosis through the mitochondrial pathway. Dose-dependent suppression of the migration of cancer cells and the formation of a vascular network were observed after treatment with 20. The acceptable microsomal stability implied that it is worth conducting further study on the analogues of 20 as novel drug candidates of CBSIs.
Assuntos
Tubulina (Proteína) , Antineoplásicos/farmacologia , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Ensaios de Seleção de Medicamentos Antitumorais , Pontos de Checagem da Fase G2 do Ciclo Celular , Humanos , Polimerização , Relação Estrutura-Atividade , Tubulina (Proteína)/metabolismo , Moduladores de Tubulina/farmacologiaRESUMO
The ballistic resistance of GFRP laminates subjected to high-velocity impact was studied. Based on the damage situation of GFRP laminate observed from the single-stage gas gun testing, the three-dimensional (3D) model combining strain rate effect and Hashin failure criterion was established, and the result presented good agreement between the simulation and experiment. Three factors, including layer angle, stacking sequence and proportion of different layer angles, were taken into consideration in the models. An orthogonal test method was used for the analysis, which can reduce the number of simulations effectively without sacrificing the accuracy of the result. The result indicated a correlation between the ballistic resistance and layouts of GFRP laminates, on which the stacking sequence contributed stronger influence. What was more, the laminate with layer angles 0°/90° and ±45° presented greater ballistic resistance than the other angle pairs, and adopting an equal proportion of different layer angles is helpful for GFRP laminates to resist impact as well.
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Anti-tubulin polymerization agents can disrupt tumor-vascular to exhibit anti-cancer potency. In this study, a series of substituted (2-(phenylamino)thieno[3,2-d]pyrimidin-4-yl)(3,4,5-trimethoxyphenyl)methanone analogues were designed and synthesized as anti-tubulin polymerization agents that interact with colchicine binding site. The anti-proliferative assay indicated that most of the target compounds displayed moderate to high potencies towards five tumor cell lines. The structure-activity relationship of these analogues was summarized. The most potent compound 14 was selected to assay its inhibition on the tubulin polymerization. 14 displayed potent inhibition against tubulin polymerization with an IC50 value of 4.1⯱â¯0.1⯵M. The colchicine competition assay demonstrated that 14 inhibited tubulin polymerization by binding to the colchicine-binding site of tubulin. The molecular modeling study elucidated the binding mode of 14 in the colchicine binding site. The result of confocal immunofluorescent study proved that 14 can quickly disrupt the microtubules of Hela cells in a concentration dependent manner. Some experiments at cellular level were conducted to investigate the effects of 14 on cellular morphology, cell colony formation, cell cycle distribution, cell apoptosis and mitochondrial changes. The results demonstrated that 14 is a potent anti-tubulin agent with strong concentration dependent effect of inhibition of colony formation, induction of G2/M arrest and induction of apoptosis through mitochondrial pathway.
Assuntos
Antineoplásicos/síntese química , Pirimidinas/síntese química , Moduladores de Tubulina/síntese química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Sítios de Ligação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Colchicina/metabolismo , Desenho de Fármacos , Humanos , Modelos Moleculares , Estrutura Molecular , Ligação Proteica , Pirimidinas/farmacologia , Relação Estrutura-Atividade , Moduladores de Tubulina/farmacologiaRESUMO
This study aims to investigate the flow and fracture behavior of aluminum alloy 6082-T6 (AA6082-T6) at different strain rates and triaxialities. Two groups of Charpy impact tests were carried out to further investigate its dynamic impact fracture property. A series of tensile tests and numerical simulations based on finite element analysis (FEA) were performed. Experimental data on smooth specimens under various strain rates ranging from 0.0001~3400 s-1 shows that AA6082-T6 is rather insensitive to strain rates in general. However, clear rate sensitivity was observed in the range of 0.001~1 s-1 while such a characteristic is counteracted by the adiabatic heating of specimens under high strain rates. A Johnson-Cook constitutive model was proposed based on tensile tests at different strain rates. In this study, the average stress triaxiality and equivalent plastic strain at facture obtained from numerical simulations were used for the calibration of J-C fracture model. Both of the J-C constitutive model and fracture model were employed in numerical simulations and the results was compared with experimental results. The calibrated J-C fracture model exhibits higher accuracy than the J-C fracture model obtained by the common method in predicting the fracture behavior of AA6082-T6. Finally, the Scanning Electron Microscope (SEM) of fractured specimens with different initial stress triaxialities were analyzed. The magnified fractographs indicate that high initial stress triaxiality likely results in dimple fracture.