The growth of algebroidal function

AbstractIn this paper, we investigate the growth relationship of algebroidal function and its coefficients, and then obtain a basic inequation between the maximum modulus function and Nevanlinna characteristic function. Finally, by using the inequation, we testify the order of entire algebroidal function is equal to that of its derived function

Identification of transcriptional mechanisms downstream of nf1 gene defeciency in malignant peripheral nerve sheath tumors

Malignant peripheral nerve sheath tumor (MPNST) is a type of soft tissue sarcoma that occurs in carriers of mutations in the neurofibromatosis type I gene (Nf1) as well as sporadically. Plexiform neurofibromas in NF1 patients have a significant risk of developing into MPNSTs leading to increased morbidity and mortality from this syndrome. Surgery is the primary intervention but it is not always effective due to the tendency of MPNSTs to infiltrate the surrounding tissue or grow in an inoperable location. Neurofibromin, the protein coded by the Nf1 gene, functions as a GTPase activating protein (GAP) whose mutation leads to constitutive activation of RAS and mitogen-activated protein kinase (MAPK) signaling in NF1 patientsf tumors. However, therapeutic targeting of RAS and MAPK have had limited success (Kalamarides, et al., 2012). In this study, we modulated NRAS, MEK1/2 and neurofibromin levels in MPNST cell lines and determined the global gene expression changes that were associated with each experimental condition. Furthermore, gene expression changes due to neurofibromin deficiency but independent of NRAS and MEK1/2 regulation were characterized for the first time in MPNST cell lines, with a focus on bone morphogenetic protein 2 (Bmp2). Experimental evidence indicated that the BMP2-SMAD1/5 pathway was activated in NF1-associated MPNST cells and inhibition of BMP2 signaling by LDN-193189 or shRNA to BMP2 decreased the motility and invasion of NF1-associated MPNST cells in vitro. The stratification of gene changes according to pathway responses has provided a clarification of one mechanism within the complex effects of neurofibromin in MPNST pathology and some novel targets for future therapeutic intervention

Julia lines of general random Dirichlet series

summary:In this paper, we consider a random entire function $f(s,\omega )$ defined by a random Dirichlet series $\sum \nolimits _{n=1}^{\infty }X_n(\omega ) {\rm e} ^{-\lambda _n s}$ where $X_n$ are independent and complex valued variables, $0\leq \lambda _n \nearrow +\infty$. We prove that under natural conditions, for some random entire functions of order $(R)$ zero $f(s,\omega )$ almost surely every horizontal line is a Julia line without an exceptional value. The result improve a theorem of J. R. Yu: Julia lines of random Dirichlet series. Bull. Sci. Math. 128 (2004), 341–353, by relaxing condition on the distribution of $X_n$ for such function $f(s,\omega )$ of order $(R)$ zero, almost surely

AOBase: a database for antisense oligonucleotides selection and design

Antisense oligonucleotides (ODNs) technology is one of the important approaches for the sequence-specific knockdown of gene expression. ODNs have been used as research tools in the post-genome era, as well as new types of therapeutic agents. Since finding effective target sites within RNA is a hard work for antisense ODNs design, various experimental methods and computational approaches have been proposed. For better sharing of the experimented and published ODNs, valid and invalid ODNs reported in literatures are screened, collected and stored in AOBase. Till now, ∼700 ODNs against 46 target mRNAs are contained in AOBase. Entries can be explored via TargetSearch and AOSearch web retrieval interfaces. AOBase can not only be useful in ODNs selection for gene function exploration, but also contribute to mining rules and developing algorithms for rational ODNs design. AOBase is freely accessible via

Selection of antisense oligonucleotides based on multiple predicted target mRNA structures

BACKGROUND: Local structures of target mRNAs play a significant role in determining the efficacies of antisense oligonucleotides (ODNs), but some structure-based target site selection methods are limited by uncertainties in RNA secondary structure prediction. If all the predicted structures of a given mRNA within a certain energy limit could be used simultaneously, target site selection would obviously be improved in both reliability and efficiency. In this study, some key problems in ODN target selection on the basis of multiple predicted target mRNA structures are systematically discussed. RESULTS: Two methods were considered for merging topologically different RNA structures into integrated representations. Several parameters were derived to characterize local target site structures. Statistical analysis on a dataset with 448 ODNs against 28 different mRNAs revealed 9 features quantitatively associated with efficacy. Features of structural consistency seemed to be more highly correlated with efficacy than indices of the proportion of bases in single-stranded or double-stranded regions. The local structures of the target site 5' and 3' termini were also shown to be important in target selection. Neural network efficacy predictors using these features, defined on integrated structures as inputs, performed well in "minus-one-gene" cross-validation experiments. CONCLUSION: Topologically different target mRNA structures can be merged into integrated representations and then used in computer-aided ODN design. The results of this paper imply that some features characterizing multiple predicted target site structures can be used to predict ODN efficacy

Identification of genes regulated by Wnt/β-catenin pathway and involved in apoptosis via microarray analysis

BACKGROUND: Wnt/β-catenin pathway has critical roles in development and oncogenesis. Although significant progress has been made in understanding the downstream signaling cascade of this pathway, little is known regarding Wnt/β-catenin pathway modification of the cellular apoptosis. METHODS: To identify potential genes regulated by Wnt/β-catenin pathway and involved in apoptosis, we used a stably integrated, inducible RNA interference (RNAi) vector to specific inhibit the expression and the transcriptional activity of β-catenin in HeLa cells. Meanwhile, we designed an oligonucleotide microarray covering 1384 apoptosis-related genes. Using oligonucleotide microarrays, a series of differential expression of genes was identified and further confirmed by RT-PCR. RESULTS: Stably integrated inducible RNAi vector could effectively suppress β-catenin expression and the transcriptional activity of β-catenin/TCF. Meanwhile, depletion of β-catenin in this manner made the cells more sensitive to apoptosis. 130 genes involved in some important cell-apoptotic pathways, such as PTEN-PI3K-AKT pathway, NF-κB pathway and p53 pathway, showed significant alteration in their expression level after the knockdown of β-catenin. CONCLUSION: Coupling RNAi knockdown with microarray and RT-PCR analyses proves to be a versatile strategy for identifying genes regulated by Wnt/β-catenin pathway and for a better understanding the role of this pathway in apoptosis. Some of the identified β-catenin/TCF directed or indirected target genes may represent excellent targets to limit tumor growth