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

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

Quantum transport at the Dirac point: Mapping out the minimum conductivity from pristine to disordered graphene

The phase space for graphene's minimum conductivity $\sigma_\mathrm{min}$ is mapped out using Landauer theory modified for scattering using Fermi's Golden Rule, as well as the Non-Equilibrium Green's Function (NEGF) simulation with a Monte Carlo sampling over impurity distributions. The resulting `fan diagram' spans the range from ballistic to diffusive over varying aspect ratios ($W/L$), and bears several surprises. {The device aspect ratio determines how much tunneling (between contacts) is allowed and becomes the dominant factor for the evolution of $\sigma_{min}$ from ballistic to diffusive regime. We find an increasing (for $W/L>1$) or decreasing ($W/L<1$) trend in $\sigma_{min}$ vs. impurity density, all converging around $128q^2/\pi^3h\sim 4q^2/h$ at the dirty limit}. In the diffusive limit, the {conductivity} quasi-saturates due to the precise cancellation between the increase in conducting modes from charge puddles vs the reduction in average transmission from scattering at the Dirac Point. In the clean ballistic limit, the calculated conductivity of the lowest mode shows a surprising absence of Fabry-P\'{e}rot oscillations, unlike other materials including bilayer graphene. We argue that the lack of oscillations even at low temperature is a signature of Klein tunneling

Strength, Toughness, Damage And Fatigue Of Rock

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