In an event-related functional MRI data analysis, an accurate and robust extraction of the hemodynamic response function (HRF) and its associated statistics (e.g., magnitude, width, and time to peak) is critical to infer quantitative information about the relative timing of the neuronal events in different brain regions. The aim of this paper is to develop a multiscale adaptive smoothing model (MASM) to accurately estimate HRFs pertaining to each stimulus sequence across all voxels. MASM explicitly accounts for both spatial and temporal smoothness information, while incorporating such information to adaptively estimate HRFs in the frequency domain. One simulation study and a real data set are used to demonstrate the methodology and examine its finite sample performance in HRF estimation, which confirms that MASM significantly outperforms the existing methods including the smooth finite impulse

One great challenge of genomic research is to efficiently and accurately identify complex gene regulatory networks. The development of high-throughput technologies provides numerous experimental data such as DNA sequences, protein sequence, and RNA expression profiles makes it possible to study interactions and regulations among genes or other substance in an organism. However, it is crucial to make inference of genetic regulatory networks from gene expression profiles and protein interaction data for systems biology. This study will develop a new approach to reconstruct time delay Boolean networks as a tool for exploring biological pathways. In the inference strategy, we will compare all pairs of input genes in those basic relationships by their corresponding -scores for every output gene. Then, we will combine those consistent relationships to reveal the most probable relationship and reconstruct the genetic network. Specifically, we will prove that state transition pairs are sufficient and necessary to reconstruct the time delay Boolean network of nodes with high accuracy if the number of input genes to each gene is bounded. We also have implemented this method on simulated and empirical yeast gene expression data sets. The test results show that this proposed method is extensible for realistic networks.

<b>Motivation:</b> Normalization of microarray data is essential for multiple-array analyses. Several normalization protocols have been proposed based on different biological or statistical assumptions. A fundamental problem arises whether they have effectively normalized arrays. In addition, for a given array, the question arises how to choose a method to most effectively normalize the microarray data.

DNA microarray analysis has emerged as a leading technology to enhance our understanding of gene regulation and function in cellular mechanism controls on a genomic scale. This technology has advanced to unravel the genetic machinery of biological rhythms by collecting massive gene-expression data in a time course. Here, we present a statistical model for clustering periodic patterns of gene expression in terms of different transcriptional profiles. The model incorporates biologically meaningful Fourier series approximations of gene periodic expression into a mixture-model-based likelihood function, thus producing results that are likely to be closer to biological relevance, as compared to those from existing models. Also because the structures of the time-dependent means and covariance matrix are modeled, the new approach displays increased statistical power and precision of parameter estimation. The

Stem cell therapies have had tremendous potential application for many diseases in recent years. However, the tumorigeneic properties of stem cells restrict their potential clinical application; therefore, strategies for reducing the tumorigenic potential of stem cells must be established prior to transplantation. We have demonstrated that syngeneic transplantation of embryonic stem cells (ESCs) provokes an inflammatory response that involves the rapid recruitment of bone marrow-derived macrophages (BMDMs). ESCs are able to prevent mature macrophages from macrophage colony-stimulating factor (M-CSF) withdrawal-induced apoptosis, and thus prolong macrophage lifespan significantly by blocking various apoptotic pathways in an M-CSF-independent manner. ESCs express and secrete IL-34 which may be responsible for ESC-promoted macrophage survival. This anti-apoptotic effect of ESCs involves activation of extracellular signal-regulated kinase (ERK)1/2 and PI3K/Akt pathways and thus, inhibition of ERK1/2 and PI3K/AKT activation decreases ESC-induced macrophage survival. Functionally, ESC-treated macrophages also showed a higher level of phagocytic activity. ESCs further serve to polarize BMDMs into M2-like macrophages that exhibit most tumor-associated macrophage (TAM) phenotypic and functional features. ESC-educated macrophages produce high levels of arginase-1, Tie-2 and TNF-, which participate in angiogenesis and contribute to teratoma progression. Our study suggests that induction of M2-like macrophage activation is an important mechanism for teratoma development. Strategies targeting macrophages to