This study addresses the effectiveness of a simple stiffness tailoring concept to delay damage initiation, control damage progression, and improve residual strength in tensile-loaded composite plates with a central circular cutout. The tailoring concept is to simply reposit all axially oriented (0°) material into regions near the edge of the plate away from the cutout. This tailoring is done in a way so as not to affect the weight of the plate. This accomplishes several beneficial changes in the way that the plate resists loading with no increases in material cost or weight. Lowering the axial stiffness of the laminate surrounding the cutout lowers the stress concentration. Increasing the axial stiffness near edges of the plate attracts loading away from the vicinity of the cutout to further lower stresses in the critical cutout region. This study focuses on in-plane response including damage progression and residual strength as a function of the degree of tailoring and cutout size. Strength and stiffness properties typical of IM7/8551-7 preperg material were assumed and a modified version of the Hashin failure criteria was used to identify the local damage. Results show that tailoring can significantly increase the damage initiation load and the residual strength. In some cases, observed evidence shows that tailoring performs as a damage arrest mechanism. 相似文献
Exorbitant aldosterone is closely associated with various severe diseases, including congestive heart failure and chronic kidney disease. As aldosterone synthase is the pivotal enzyme in aldosterone biosynthesis, its inhibition constitutes a promising treatment for these diseases. Via a structure-based approach, a series of pyridyl substituted 3,4-dihydrobenzo[f][1,4]oxazepin-5(2H)-ones were designed as inhibitors of aldosterone synthase. Six compounds (5j, 5l, 5m 5w, 5x and 5y) distinguished themselves with potent inhibition (IC50 <100 nmol/L) and high selectivity over homogenous 11β-hydroxylase. As the most promising compound, 5x exhibited an IC50 of 12 nmol/L and an excellent selectivity factor (SF) of 157, which are both superior to those of the reference fadrazole (IC50 = 21 nmol/L, SF = 7). Importantly, 5x showed no inhibition against steroidogenic CYP17, CYP19 and a panel of hepatic CYP enzymes indicating an outstanding safety profile. As it manifested satisfactory pharmacokinetic properties in rats, compound 5x was considered as a drug candidate for further development. 相似文献