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In this paper, a new higher-order shear and normal deformation theory for the bending and free vibration analysis of sandwich plates with functionally graded isotropic face sheets is developed. The number of unknown functions involved in the present theory is only five, as against six or more in case of other shear and normal deformation theories. The theory accounts for hyperbolic distribution of the transverse shear strains and satisfies the zero traction boundary conditions on the surfaces of the plate without using shear correction factor. The boundary conditions for the plate are assumed to be simply supported in all edges and in the static analysis, the plate is assumed to be subjected to a sinusoidally distributed load. Both symmetric and non-symmetric sandwich plates are considered. The equations of motion are obtained using Hamilton’s principle. Numerical results of present theory are compared with three-dimensional elasticity solutions and other higher-order theories reported in the literature. It can be concluded that the proposed theory is accurate and efficient in predicting the bending and free vibration responses of sandwich plates with functionally graded isotropic face sheets.

It has been hypothesized that continuously releasing drug molecules into the tumor over an extended period of time may significantly improve the chemotherapeutic efficacy by overcoming physical transport limitations of conventional bolus drug treatment. In this paper, we present a generalized space- and time-dependent mathematical model of drug transport and drug-cell interactions to quantitatively formulate this hypothesis. Model parameters describe: perfusion and tissue architecture (blood volume fraction and blood vessel radius); diffusion penetration distance of drug (i.e., a function of tissue compactness and drug uptake rates by tumor cells); and cell death rates (as function of history of drug uptake). We performed preliminary testing and validation of the mathematical model using in vivo experiments with different drug delivery methods on a breast cancer mouse model. Experimental data demonstrated a 3-fold increase in response using nano-vectored drug vs. free drug delivery, in excellent quantitative agreement with the model predictions. Our model results implicate that therapeutically targeting blood volume fraction, e.g., through vascular normalization, would achieve a better outcome due to enhanced drug delivery.Author SummaryCancer treatment efficacy can be significantly enhanced through the elution of drug from nano-carriers that can temporarily stay in the tumor vasculature. Here we present a relatively simple yet powerful mathematical model that accounts for both spatial and temporal heterogeneities of drug dosing to help explain, examine, and prove this concept. We find that the delivery of systemic chemotherapy through a certain form of nano-carriers would have enhanced tumor kill by a factor of 2 to 4 over the standard therapy that the patients actually received. We also find that targeting blood volume fraction (a parameter of the model) through vascular normalization can achieve more effective drug delivery and tumor kill. More importantly, this model only requires a limited number of parameters which can all be readily assessed from standard clinical diagnostic measurements (e.g., histopathology and CT). This addresses an important challenge in current translational research and justifies further development of the model towards clinical translation.

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In this study, a new shear deformation plate theory is introduced to illustrate the bending, buckling and free vibration responses of functionally graded material sandwich plates. A new displacement field containing integrals is proposed which involves only four variables. Based on the suggested theory, the equations of motion are derived from Hamilton’s principle. This theory involves only four unknown functions and accounts for quasi-parabolic distribution of transverse shear stress. In addition, the transverse shear stresses are vanished at the top and bottom surfaces of the sandwich plate. The Navier solution technique is adopted to derive analytical solutions for simply supported rectangular sandwich plates. The accuracy and effectiveness of proposed model are verified by comparison with previous research. A detailed numerical study is carried out to examine the influence of the critical buckling loads, deflections, stresses, natural frequencies and sandwich plate type on the bending, buckling and free vibration responses of functionally graded sandwich plates.

We combine mathematical modeling with experiments in living mice to quantify the relative roles of intrinsic cellular vs. tissue-scale physiological contributors to chemotherapy drug resistance, which are difficult to understand solely through experimentation. Experiments in cell culture and in mice with drug-sensitive (Eµ-myc/Arf-/-) and drug-resistant (Eµ-myc/p53-/-) lymphoma cell lines were conducted to calibrate and validate a mechanistic mathematical model. Inputs to inform the model include tumor drug transport characteristics, such as blood volume fraction, average geometric mean blood vessel radius, drug diffusion penetration distance, and drug response in cell culture. Model results show that the drug response in mice, represented by the fraction of dead tumor volume, can be reliably predicted from these inputs. Hence, a proof-of-principle for predictive quantification of lymphoma drug therapy was established based on both cellular and tissue-scale physiological contributions. We further demonstrate that, if the in vitro cytotoxic response of a specific cancer cell line under chemotherapy is known, the model is then able to predict the treatment efficacy in vivo. Lastly, tissue blood volume fraction was determined to be the most sensitive model parameter and a primary contributor to drug resistance.