Status of the differential transformation method

Further to a recent controversy on whether the differential transformation method (DTM) for solving a differential equation is purely and solely the traditional Taylor series method, it is emphasized that the DTM is currently used, often only, as a technique for (analytically) calculating the power series of the solution (in terms of the initial value parameters). Sometimes, a piecewise analytic continuation process is implemented either in a numerical routine (e.g., within a shooting method) or in a semi-analytical procedure (e.g., to solve a boundary value problem). Emphasized also is the fact that, at the time of its invention, the currently-used basic ingredients of the DTM (that transform a differential equation into a difference equation of same order that is iteratively solvable) were already known for a long time by the "traditional"-Taylor-method users (notably in the elaboration of software packages --numerical routines-- for automatically solving ordinary differential equations). At now, the defenders of the DTM still ignore the, though much better developed, studies of the "traditional"-Taylor-method users who, in turn, seem to ignore similarly the existence of the DTM. The DTM has been given an apparent strong formalization (set on the same footing as the Fourier, Laplace or Mellin transformations). Though often used trivially, it is easily attainable and easily adaptable to different kinds of differentiation procedures. That has made it very attractive. Hence applications to various problems of the Taylor method, and more generally of the power series method (including noninteger powers) has been sketched. It seems that its potential has not been exploited as it could be. After a discussion on the reasons of the "misunderstandings" which have caused the controversy, the preceding topics are concretely illustrated.Comment: To appear in Applied Mathematics and Computation, 29 pages, references and further considerations adde

Solving an Optimal Control Problem of Cancer Treatment by Artificial Neural Networks

Cancer is an uncontrollable growth of abnormal cells in any tissue of the body. Many researchers have focused on machine learning and artificial intelligence (AI) based on approaches for cancer treatment. Dissimilar to traditional methods, these approaches are efficient and are able to find the optimal solutions of cancer chemotherapy problems. In this paper, a system of ordinary differential equations (ODEs) with the state variables of immune cells, tumor cells, healthy cells and drug concentration is proposed to anticipate the tumor growth and to show their interactions in the body. Then, an artificial neural network (ANN) is applied to solve the ODEs system through minimizing the error function and modifying the parameters consisting of weights and biases. The mean square errors (MSEs) between the analytical and ANN results corresponding to four state variables are 1.54e-06, 6.43e-07, 6.61e-06, and 3.99e-07, respectively. These results show the good performance and efficiency of the proposed method. Moreover, the optimal dose of chemotherapy drug and the amount of drug needed to continue the treatment process are achieved

Multilevel Markov Chain Monte Carlo Method for High-Contrast Single-Phase Flow Problems

In this paper we propose a general framework for the uncertainty quantification of quantities of interest for high-contrast single-phase flow problems. It is based on the generalized multiscale finite element method (GMsFEM) and multilevel Monte Carlo (MLMC) methods. The former provides a hierarchy of approximations of different resolution, whereas the latter gives an efficient way to estimate quantities of interest using samples on different levels. The number of basis functions in the online GMsFEM stage can be varied to determine the solution resolution and the computational cost, and to efficiently generate samples at different levels. In particular, it is cheap to generate samples on coarse grids but with low resolution, and it is expensive to generate samples on fine grids with high accuracy. By suitably choosing the number of samples at different levels, one can leverage the expensive computation in larger fine-grid spaces toward smaller coarse-grid spaces, while retaining the accuracy of the final Monte Carlo estimate. Further, we describe a multilevel Markov chain Monte Carlo method, which sequentially screens the proposal with different levels of approximations and reduces the number of evaluations required on fine grids, while combining the samples at different levels to arrive at an accurate estimate. The framework seamlessly integrates the multiscale features of the GMsFEM with the multilevel feature of the MLMC methods following the work in \cite{ketelson2013}, and our numerical experiments illustrate its efficiency and accuracy in comparison with standard Monte Carlo estimates.Comment: 29 pages, 6 figure

Model-based optimization of batch- and continuous crystallization processes

Crystallization is an important separation process, extensively used in most chemical industries and especially in pharmaceutical manufacturing, either as a method of production or as a method of purification or recovery of solids. Typically, crystallization can have a considerable impact on tuning the critical quality attributes (CQAs), such as crystal size and shape distribution (CSSD), purity and polymorphic form, that impact the final product quality performance indicators and inherent end-use properties, along with the downstream processability. Therefore, one of the critical targets in controlled crystallization processes, is to engineer specific properties of the final product. The purpose of this research is to develop systematic computer-aided methodologies for the design of batch and continuous mixed suspension mixed product removal (MSMPR) crystallization processes through the implementation of simulation models and optimization frameworks. By manipulating the critical process parameters (CPPs), the achievable range of CQAs and the feasible design space (FDS) can be identified. Paracetamol in water and potassium dihydrogen phosphate (KDP) in water are considered as the model chemical systems.The studied systems are modeled utilizing single and multi-dimensional population balance models (PBMs). For the batch crystallization systems, single and multi-objective optimization was carried out for the determination of optimal operating trajectories by considering mean crystal size, the distribution s standard deviation and the aspect ratio of the population of crystals, as the CQAs represented in the objective functions. For the continuous crystallization systems, the attainable region theory is employed to identify the performance of multi-stage MSMPRs for various operating conditions and configurations. Multi-objective optimization is also applied to determine a Pareto optimal attainable region with respect to multiple CQAs. By identifying the FDS of a crystallization system, the manufacturing capabilities of the process can be explored, in terms of mode of operation, CPPs, and equipment configurations, that would lead to the selection of optimum operation strategies for the manufacturing of products with desired CQAs under certain manufacturing and supply chain constraints. Nevertheless, developing reliable first principle mathematical models for crystallization processes can be very challenging due to the complexity of the underlying phenomena, inherent to population balance models (PBMs). Therefore, a novel framework for parameter estimability for guaranteed optimal model reliability is also proposed and implemented. Two estimability methods are combined and compared: the first is based on a sequential orthogonalization of the local sensitivity matrix and the second is Sobol, a variance-based global sensitivities technic. The framework provides a systematic way to assess the quality of two nominal sets of parameters: one obtained from prior knowledge and the second obtained by simultaneous identification using global optimization. A multi-dimensional population balance model that accounts for the combined effects of different crystal growth modifiers/ impurities on the crystal size and shape distribution of needle-like crystals was used to validate the methodology. A cut-off value is identified from an incremental least square optimization procedure for both estimability methods, providing the required optimal subset of model parameters. In addition, a model-based design of experiments (MBDoE) methodology approach is also reported to determine the optimal experimental conditions yielding the most informative process data. The implemented methodology showed that, although noisy aspect ratio data were used, the eight most influential and least correlated parameters could be reliably identified out of twenty-three, leading to a crystallization model with enhanced prediction capability. A systematic model-based optimization methodology for the design of crystallization processes under the presence of multiple impurities is also investigated. Supersaturation control and impurity inclusion is combined to evaluate the effect on the product's CQAs. To this end, a morphological PBM is developed for the modelling of the cooling crystallization of pure KDP in aqueous solution, as a model system, under the presence of two competitive crystal growth modifiers/ additives: aluminum sulfate and sodium hexametaphosphate. The effect of the optimal temperature control with and without the additives on the CQAs is presented via utilizing multi-objective optimization. The results indicate that the attainable size and shape attributes, can be considerably enhanced due to advanced operation flexibility. Especially it is shown that the shape of the KDP crystals can be affected even by the presence of small quantity of additives and their morphology can be modified from needle-like to spherical, which is more favourable for processing. In addition, the multi-impurity PBM model is extended by the utilization of a high-resolution finite volume (HR-FV) scheme, instead of the standard method of moments (SMOM), in order for the full reconstruction and dynamic modelling of the crystal size and shape distribution to be enabled. The implemented methodology illustrated the capabilities of utilizing high-fidelity computational models for the investigation of crystallization processes in impure media for process and product design and optimization purposes