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

Adjuvant COX inhibition augments STING signaling and cytolytic T cell infiltration in irradiated 4T1 tumors

Immune therapy is the new frontier of cancer treatment. Therapeutic radiation is a known inducer of immune response and can be limited by immunosuppressive mediators including cyclooxygenase-2 (COX2) that is highly expressed in aggressive triple negative breast cancer (TNBC). A clinical cohort of TNBC tumors revealed poor radiation therapeutic efficacy in tumors expressing high COX2. Herein, we show that radiation combined with adjuvant NSAID (indomethacin) treatment provides a powerful combination to reduce both primary tumor growth and lung metastasis in aggressive 4T1 TNBC tumors, which occurs in part through increased antitumor immune response. Spatial immunological changes including augmented lymphoid infiltration into the tumor epithelium and locally increased cGAS/STING1 and type I IFN gene expression were observed in radiation-indomethacin–treated 4T1 tumors. Thus, radiation and adjuvant NSAID treatment shifts “immune desert phenotypes” toward antitumor M1/TH1 immune mediators in these immunologically challenging tumors. Importantly, radiation-indomethacin combination treatment improved local control of the primary lesion, reduced metastatic burden, and increased median survival when compared with radiation treatment alone. These results show that clinically available NSAIDs can improve radiation therapeutic efficacy through increased antitumor immune response and augmented local generation of cGAS/STING1 and type I IFNs

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