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Pseudo-transient continuation is a practical technique for globalizing the computation of steady-state solutions of nonlinear differential equations. The technique employs adaptive time-stepping to integrate an initial value problem derived from an underlying ODE or PDE boundary value problem until sufficient accuracy in the desired steady-state root is(More)
In this paper, we explore in detail the stability properties of time-domain numerical methods for multi-time partial differential equations (MPDEs). We demonstrate that simple techniques for numerical discretization can lead easily to instability. By investigating the underlying eigenstructure of several discretization techniques along different artificial(More)
OX40 is a potent costimulatory receptor that can potentiate T-cell receptor signaling on the surface of T lymphocytes, leading to their activation by a specifically recognized antigen. In particular, OX40 engagement by ligands present on dendritic cells dramatically increases the proliferation, effector function, and survival of T cells. Preclinical studies(More)
We consider the simulation of steady-state variably saturated groundwater flow using Richards' equation (RE). The difficulties associated with solving RE numerically are well known. Most discretization approaches for RE lead to nonlinear systems that are large and difficult to solve. The solution of nonlinear systems for steady-state problems can be(More)
The ability to automatically morph an existing mesh to conform to geometry modifications is a necessary capability to enable rapid prototyping of design variations. This paper compares six methods for morphing hexahe-dral and tetrahedral meshes, including the previously published FEMWARP and LBWARP methods as well as four new methods. Element quality and(More)
Amylin infusion reduces food intake and slows body weight gain in rodents. In obese male rats, amylin (but not pair feeding) caused a preferential reduction of fat mass with protein preservation despite equal body weight loss in amylin-treated (fed ad libitum) and pair-fed rats. In the present study, the effect of prior or concurrent food restriction on the(More)
Protein therapeutics have unique critical quality attributes (CQAs) that define their purity, potency, and safety. The analytical methods used to assess CQAs must be able to distinguish clinically meaningful differences in comparator products, and the most important CQAs should be evaluated with the most statistical rigor. High-risk CQA measurements assess(More)
For biosimilar drug development, it is critical to demonstrate similar physiochemical characteristics, efficacy, and safety of the biosimilar product compared to the reference product. Therefore, pharmacokinetic (PK) and immunogenicity (antidrug antibody, ADA) assays that allow for the demonstration of biosimilarity are critical. Under the auspices of the(More)
Traditional factorial designs for evaluating interactions among chemicals in a mixture may be prohibitive when the number of chemicals is large. Using a mixture of chemicals with a fixed ratio (mixture ray) results in an economical design that allows estimation of additivity or nonadditive interaction for a mixture of interest. This methodology is extended(More)