The quantitative comparison of two or more microarrays can reveal, for example, the distinct patterns of gene expression that define different cellular phenotypes or the genes that are induced in the cellular response to certain stimulations. Normalization of the measured intensities is a prerequisite of such comparisons. However, a fundamental problem in cDNA microarray analysis is the lack of a common standard to compare the expression levels of different samples. Several normalization protocols have been proposed to overcome the variabilities inherent in this technology. We have developed a normalization procedure based on within-array replications via a semilinear in-slide model, which adjusts objectively experimental variations without making critical biological assumptions. The significant analysis of gene expressions is based on a weighted <i>t</i> statistic, which accounts for the heteroscedasticity of the

Microarray techniques have been widely used to monitor gene expression in many areas of biomedical research. They have been widely used for tumor diagnosis and classification, prediction of prognoses and treatment, and understanding of molecular mechanisms, biochemical pathways, and gene networks. Statistical methods are vital for these scientific endeavors. This article reviews recent developments of statistical methods for analyzing data from microarray experiments. Emphasis has been given to normalization of expression from multiple arrays, selecting significantly differentially expressed genes, tumor classifications, and gene expression pathways and networks.

Severe acute respiratory syndrome (SARS) is a new infectious disease with a global impact. Understanding its pathogenesis and developing specific diagnostic methods for its early diagnosis are crucial for the effective management and control of this disease. By using proteomic technology, truncated forms of ₁antitrypsin (TF₁AT) were found to increase significantly and consistently in sera of SARS patients compared to control subjects. The result showed a sensitivity of 100% for SARS patients and a specificity of 92.8% for controls. Furthermore, the levels of these proteins significantly correlated with certain clinicopathological parameters. The dramatic increase in TF₁AT may be the result of degradation of ₁AT. As ₁AT plays an important role in the protection of lung function, its degradation may be an important factor in the pathogenesis of SARS. These findings indicate that increased TF₁AT

It has been reported that the plasma levels of VEGF in tumor patients decreased during dendritic cell (DC)-based immunotherapy, but the underlying mechanism remains unclear. Our current report demonstrates that VEGF levels were significantly decreased in the supernatants of DCs incubated with rhVEGF or tumor conditioned medium (TCM) while the intracellular VEGF in DCs was increased. The increased intracellular VEGF was not due to the <i>de novo</i> VEGF synthesis by DCs because exogenous VEGF inhibited the mRNA expression of VEGF in DCs. More direct evidence was provided to demonstrate that Cy3-labeled VEGF could be internalized by DCs specifically and efficiently. In addition, the activity of DCs to internalize VEGF was abolished by neutralizing antibody against VEGF receptor-1 (Flt-1) and inhibitors of endocytosis such as carbonyl cyanide m-chlorophenyl hydrazone (CCCP) and genistein. This

We study a class of nonlinear nonlocal cochlear models of the transmission line type, describing the motion of basilar membrane (BM) in the cochlea. They are damped dispersive partial differential equations (PDEs) driven by time dependent boundary forcing due to the input sounds. The global well-posedness in time follows from energy estimates. Uniform bounds of solutions hold in the case of bounded nonlinear damping. When the input sounds are multi-frequency tones, and the nonlinearity in the PDEs is cubic, we construct smooth quasi-periodic solutions (multi-tone solutions) in the weakly nonlinear regime, where new frequencies are generated due to nonlinear interaction. When the input consists of two tones at frequencies f 1, f 2 (f 1&lt; f 2), and high enough intensities, numerical results illustrate the formation of combination tones at 2f 1 f 2 and 2f 2 f 1, in agreement with hearing experiments. We visualize