8,125 research outputs found

    Gene Expression Profile Changes After Short-activating RNA-mediated Induction of Endogenous Pluripotency Factors in Human Mesenchymal Stem Cells

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    It is now recognized that small noncoding RNA sequences have the ability to mediate transcriptional activation of specific target genes in human cells. Using bioinformatics analysis and functional screening, we screened short-activating RNA (saRNA) oligonucleotides designed to target the promoter regions of the pluripotency reprogramming factors, Kruppel-like factor 4 (KLF4) and c-MYC. We identified KLF4 and c-MYC promoter-targeted saRNA sequences that consistently induced increases in their respective levels of nascent mRNA and protein expression in a time- and dose-dependent manner, as compared with scrambled sequence control oligonucleotides. The functional consequences of saRNA-induced activation of each targeted reprogramming factor were then characterized by comprehensively profiling changes in gene expression by microarray analysis, which revealed significant increases in mRNA levels of their respective downstream pathway genes. Notably, the microarray profile after saRNA-mediated induction of endogenous KLF4 and c-MYC showed similar gene expression patterns for stem cell- and cell cycle-related genes as compared with lentiviral vector-mediated overexpression of exogenous KLF4 and c-MYC transgenes, while divergent gene expression patterns common to viral vector-mediated transgene delivery were also noted. The use of promoter-targeted saRNAs for the activation of pluripotency reprogramming factors could have broad implications for stem cell research

    Strength, Toughness, Damage And Fatigue Of Rock

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    Assessment of rock mechanical properties depends on sample size and testing methodologies. Even for samples cored from the same rock outcrop the difference in properties appears to be sensitive to the local thermal and stress histories of the rock structure. Variations in the fracture toughness, unconfined compressive strength and tensile strength of a suite of granite samples, when tested using different procedures, are discussed in terms of experimental errors of the loading system as well as the thermal history

    Performance of modified non-linear shooting method for simulation of 2nd order two-point BVPS

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    In this research article, numerical solution of nonlinear 2nd order two-point boundary value problems (TPBVPs) is discussed by the help of nonlinear shooting method (NLSM), and through the modified nonlinear shooting method (MNLSM). In MNLSM, fourth order Runge-Kutta method for systems is replaced by Adams Bashforth Moulton method which is a predictor-corrector scheme. Results acquired numerically through NLSM and MNLSM of TPBVPs are discussed and analyzed. Results of the tested problems obtained numerically indicate that the performance of MNLSM is rapid and provided desirable results of TPBVPs, meanwhile MNLSM required less time to implement as comparable to the NLSM for the solution of TPBVPs

    Colourings of cubic graphs inducing isomorphic monochromatic subgraphs

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    A kk-bisection of a bridgeless cubic graph GG is a 22-colouring of its vertex set such that the colour classes have the same cardinality and all connected components in the two subgraphs induced by the colour classes (monochromatic components in what follows) have order at most kk. Ban and Linial conjectured that every bridgeless cubic graph admits a 22-bisection except for the Petersen graph. A similar problem for the edge set of cubic graphs has been studied: Wormald conjectured that every cubic graph GG with E(G)0(mod2)|E(G)| \equiv 0 \pmod 2 has a 22-edge colouring such that the two monochromatic subgraphs are isomorphic linear forests (i.e. a forest whose components are paths). Finally, Ando conjectured that every cubic graph admits a bisection such that the two induced monochromatic subgraphs are isomorphic. In this paper, we give a detailed insight into the conjectures of Ban-Linial and Wormald and provide evidence of a strong relation of both of them with Ando's conjecture. Furthermore, we also give computational and theoretical evidence in their support. As a result, we pose some open problems stronger than the above mentioned conjectures. Moreover, we prove Ban-Linial's conjecture for cubic cycle permutation graphs. As a by-product of studying 22-edge colourings of cubic graphs having linear forests as monochromatic components, we also give a negative answer to a problem posed by Jackson and Wormald about certain decompositions of cubic graphs into linear forests.Comment: 33 pages; submitted for publicatio
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