Adult stem cells, which exist throughout the body, multiply by cell division to replenish dying cells or to promote regeneration to repair damaged tissues. To perform these functions during the lifetime of organs or tissues, stem cells need to maintain their populations in a faithful distribution of their epigenetic states, which are suscepti- ble to stochastic fluctuations during each cell division, unexpected injury, and potential genetic mutations that occur during many cell divisions. However, it remains unclear how the three processes of differentiation, proliferation, and apoptosis in regulating stem cells collectively manage these challenging tasks. Here, without consid- ering molecular details, we propose a genetic optimal control model for adult stem cell regeneration that includes the three fundamental processes, along with cell division and adaptation based on differ- ential fitnesses of phenotypes. In the model, stem cells with a distri- bution of epigenetic states are required to maximize expected performance after each cell division. We show that heteroge- neous proliferation that depends on the epigenetic states of stem cells can improve the maintenance of stem cell distributions to create balanced populations. A control strategy during each cell division leads to a feedback mechanism involving heterogeneous proliferation that can accelerate regeneration with less fluctuation in the stem cell population. When mutation is allowed, apoptosis evolves to maximize the performance during homeostasis after multiple cell divisions. The overall results highlight the importance of cross-talk between genetic and epigenetic regulation and the performance objectives during homeostasis in shaping a desirable heterogeneous distribution of stem cells in epigenetic states.

High dimensionality comparable to sample size is common in many statistical problems. We examine covariance matrix estimation in the asymptotic framework that the dimensionality p tends to as the sample size n increases. Motivated by the Arbitrage Pricing Theory in finance, a multi-factor model is employed to reduce dimensionality and to estimate the covariance matrix. The factors are observable and the number of factors K is allowed to grow with p. We investigate the impact of p and K on the performance of the model-based covariance matrix estimator. Under mild assumptions, we have established convergence rates and asymptotic normality of the model-based estimator. Its performance is compared with that of the sample covariance matrix. We identify situations under which the factor approach increases performance substantially or marginally. The impacts of covariance matrix estimation on optimal

In this paper, high order central finite difference schemes in a finite interval are analyzed for the diffusion equation. Boundary conditions of the initial-boundary value problem (IBVP) are treated by the simplified inverse Lax-Wendroff (SILW) procedure. For the fully discrete case, a third order explicit Runge-Kutta method is used as an example for the analysis. Stability is analyzed by both the GKS (Gustafsson, Kreiss and Sundstr\"om) theory and the eigenvalue visualization method on both semi-discrete and fully discrete schemes. The two different analysis techniques yield consistent results. Numerical tests are performed to demonstrate and validate the analysis results.

In this paper we connect Calderón and Zygmund’s notion of Lp-differentiability (Calderón and Zygmund, Proc Natl Acad Sci USA 46:1385–1389, 1960) with some recent characterizations of Sobolev spaces via the asymptotics of non-local functionals due to Bourgain, Brezis, and Mironescu (Optimal Control and Partial Differential Equations, pp. 439–455, 2001). We show how the results of the former can be generalized to the setting of the latter, while the latter results can be strengthened in the spirit of the former. As a consequence of these results we give several new characterizations of Sobolev spaces, a novel condition for whether a function of bounded variation is in the Sobolev space W1,1, and complete the proof of a characterization of the Sobolev spaces recently claimed in (Leoni and Spector, J Funct Anal 261:2926–2958, 2011; Leoni and Spector, J Funct Anal 266:1106–1114, 2014).

Some filtrations of the tensor product of a highest weight module and a lowest weight module over quantum group Uq(g)are constructed in[1]and one can use them to define a two-sided ideal of the modified quantized enveloping algebra. It is shown that the quotient algebra inherits a canonical basis from the modified quantized enveloping algebra and is dual to the quantum coordinate algebra defined by Kashiwara for a symmetrizable Kac–Moody algebra g.