Optimal Cost-Analysis and Design of Circular Footings

The study pertains to the optimal cost-analysis and design of a circular footing subjected to generalized loadings using sequential unconstrained minimization technique (SUMT) in conjunction with Powell’s conjugate direction method for multidimensional search and quadratic interpolation method for one dimensional minimization. The cost of the footing is minimized satisfying all the structural and geotechnical engineering design considerations. As extended penalty function method has been used to convert the constrained problem into an unconstrained one, the developed technique is capable of handling both feasible and infeasible initial design vector. The net saving in cost starting from the best possible manual design ranges from 10 to 20 %. For all practical purposes, the optimum cost is independent of the initial design point. It was observed that for better convergence, the transition parameter  should be chosen at least 100 times the initial penalty parameter kr

Optimal Cost-Analysis and Design of Circular Footings

The study pertains to the optimal cost-analysis and design of a circular footing subjected to generalized loadings using sequential unconstrained minimization technique (SUMT) in conjunction with Powell’s conjugate direction method for multidimensional search and quadratic interpolation method for one dimensional minimization. The cost of the footing is minimized satisfying all the structural and geotechnical engineering design considerations. As extended penalty function method has been used to convert the constrained problem into an unconstrained one, the developed technique is capable of handling both feasible and infeasible initial design vector. The net saving in cost starting from the best possible manual design ranges from 10 to 20 %. For all practical purposes, the optimum cost is independent of the initial design point. It was observed that for better convergence, the transition parameter should be chosen at least 100 times the initial penalty parameter kr

Optimal Cost-Analysis and Design of Circular Footings

The study pertains to the optimal cost-analysis and design of a circular footing subjected to generalized loadings using sequential unconstrained minimization technique (SUMT) in conjunction with Powell’s conjugate direction method for multidimensional search and quadratic interpolation method for one dimensional minimization. The cost of the footing is minimized satisfying all the structural and geotechnical engineering design considerations. As extended penalty function method has been used to convert the constrained problem into an unconstrained one, the developed technique is capable of handling both feasible and infeasible initial design vector. The net saving in cost starting from the best possible manual design ranges from 10 to 20 %. For all practical purposes, the optimum cost is independent of the initial design point. It was observed that for better convergence, the transition parameter  should be chosen at least 100 times the initial penalty parameter kr

Role of nitric oxide in pancreatic cancer cells exhibiting the invasive phenotype

Pancreatic cancer is a highly metastatic tumor with an extremely low 5-year survival rate. Lack of efficient diagnostics and dearth of effective therapeutics that can target the cancer as well as the microenvironment niche are the reasons for limited success in treatment and management of this disease. Cell invasion through extracellular matrix (ECM) involves the complex regulation of adhesion to and detachment from ECM and its understanding is critical to metastatic potential of pancreatic cancer. To understand the characteristics of these cancer cells and their ability to metastasize, we compared human pancreatic cancer cell line, PANC-1 and its invading phenotype (INV) collected from transwell inserts. The invasive cell type, INV, exhibited higher resistance to Carbon-ion radiation compared to whole cultured (normally dish-cultured) PANC-1 (WCC), and had more efficient in vitro spheroid formation capability. Invasiveness of INV was hampered by nitric oxide synthase (NOS) inhibitors, suggesting that nitric oxide (NO) plays a cardinal role in PANC-1 invasion. In addition, in vitro studies indicated that a MEK-ERK-dependent, JAK independent mechanism through which NOS/NO modulate PANC-1 invasiveness. Suspended INV showed enhanced NO production as well as induction of several pro-metastatic, and stemness-related genes. NOS inhibitor, l-NAME, reduced the expression of these pro-metastatic or stemness-related genes, and dampened spheroid formation ability, suggesting that NO can potentially influence pancreatic cancer aggressiveness. Furthermore, xenograft studies with INV and WCC in NSG mouse model revealed a greater ability of INV compared to WCC, to metastasize to the liver and l-NAME diminished the metastatic lesions in mice injected with INV. Overall, data suggest that NO is a key player associated with resistance to radiation and metastasis of pancreatic cancer; and inhibition of NOS demonstrates therapeutic potential as observed in the animal model by specifically targeting the metastatic cells that harbor stem-like features and are potentially responsible for relapse. Keywords: Nitric oxide, Nitric oxide synthase, Pancreatic cancer, Invasion, Metastasis, Cancer stem cel