Although activating mutations in RAS oncogenes are known to result in aberrant signaling through multiple pathways, the role of microRNAs (miRNAs) in the Ras oncogenic program remains poorly characterized. Here we demonstrate that Ras activation leads to repression of the miR-143/145 cluster in cells of human, murine, and zebrafish origin. Loss of miR-143/145 expression is observed frequently in KRAS mutant pancreatic cancers, and restoration of these miRNAs abrogates tumorigenesis. miR-143/145 down-regulation requires the Ras-responsive element-binding protein (RREB1), which represses the miR-143/145 promoter. Additionally, KRAS and RREB1 are targets of miR-143/miR-145, revealing a feed-forward mechanism that potentiates Ras signaling.
Non-volatile memory (NVM) thin-film transistors (TFTs) with organic channels have been investigated with a ferroelectric gate material, poly(vinylidenefluoride-trifluoroethylene) [P(VDF-TrFE)] [1][2][3][4][5][6] under the basic principles from conventional Si-based ferroelectric field-effect transistors (FeFET), preparing the advent of transparent or flexible device technologies on glass and plastic substrates. Beta-phase crystalline P(VDF-TrFE) films generally have an induced remnant polarization of %10 mC cm À2 if polarized over their coercive electric field (E-field), formed through spin casting and subsequent optimum curing processes. [2,4,7] Researchers presented decent NVM properties of polymer channel NVM-TFT with P(VDF-TrFE) in their recent works: low leakage, relatively low switching voltage, [2] and a quite high switching speed. [1,2,6] They also reported the physical properties of the unit ferroelectric polymer layer. [8][9][10][11][12][13][14][15] Nonetheless, a challenging problem remains to be overcome prior to any practical application of this ferroelectric polymer towards NVM-TFT on flexible plastic or glass substrates: it is the inferior field mobility (less than %10 À2 cm 2 V À1 s
À1) of present polymer-based NVM-TFTs, which is due to the intrinsic low channel mobility of polymer-based semiconductors and also due to the rough surface of spin-cast P(VDF-TrFE) layers. Moreover, obtaining low leakage current from spin-cast crystalline ferroelectric polymer films may require quite sensitive care [2] in the solvent selection and in the coating processes of purified polymers. Our previous report shows some high mobility (0.36 cm 2 V À1 s À1 ) ZnO-based NVM-TFTs with poly-4-vinylphenol (PVP)/P(VDF-TrFE) double layers, where the PVP overlayer suppressed current leakage of P(VDF-TrFE) but also caused poor retention, inducing depolarization electric field in the ferroelectric P(VDF-TrFE) layers.[16] Here, we adopt a single P(VDF-TrFE) layer of short-range-order crystalline phase as the nonvolatile memory component for a reproducible lowcurrent-leakage ferroelectric, to be applied onto high-mobility p-channel pentacene channels on flexible plastic substrates and also onto high-mobility n-channel ZnO channels on glass. Our limited-crystalline ferroelectric layer still showed good remnant polarization of maximum %7 mC cm
À2, and the pentacene-and ZnO-based NVM-TFTs with such short-range-order crystalline P(VDF-TrFE) layer reproducibly demonstrated maximum field mobilities of 0.1 and 1 cm 2 V À1 s À1 , respectively, with low leakage current densities of a few nanoamperes (%1 Â 10 À6 A cm À2 ), low switching voltages of %20 V for write/erase (in 50 ms pulse), low operation (after switching) voltages of %5 V, and long retention of over 10000 s. In particular, our ZnO-based NVM-TFTs displayed a large memory window of 20 V, which is the maximum obtainable from 200 nm-thick P(VDF-TrFE).Device cross-sections in Figure 1a display our pentacene-and ZnO-based NVM TFTs with the short-range-order crystalline P(VDF-TrFE)...
We report on the fabrication of pentacene-based nonvolatile memory thin-film transistors (NVM-TFTs) with thin poly(vinylidene fluoride/trifluoroethylene) ferroelectric gate insulators. Our NVM-TFT adopts flexible polyethersulfone substrate and operates under the low voltage write-erase (WR-ER) pulses of ±13∼±20 V with field effect mobilities of 0.1–0.18 cm2/V s, depending on the ferroelectric polymer thickness. Our NVM-TFT displays good memory window (ΔV) of 2.5–8 V and also exhibits WR-ER current ratio of 20–40. The retention properties persist over ∼10 000 s and the dynamic response for WR-ER pulses demonstrates clear distinction of WR-ER states under the short switching pulse of 50 ms.
BackgroundSide effects are unwanted responses to drug treatment and are important resources for human phenotype information. The recent development of a database on side effects, the side effect resource (SIDER), is a first step in documenting the relationship between drugs and their side effects. It is, however, insufficient to simply find the association of drugs with biological processes; that relationship is crucial because drugs that influence biological processes can have an impact on phenotype. Therefore, knowing which processes respond to drugs that influence the phenotype will enable more effective and systematic study of the effect of drugs on phenotype. To the best of our knowledge, the relationship between biological processes and side effects of drugs has not yet been systematically researched.MethodsWe propose 3 steps for systematically searching relationships between drugs and biological processes: enrichment scores (ES) calculations, t-score calculation, and threshold-based filtering. Subsequently, the side effect-related biological processes are found by merging the drug-biological process network and the drug-side effect network. Evaluation is conducted in 2 ways: first, by discerning the number of biological processes discovered by our method that co-occur with Gene Ontology (GO) terms in relation to effects extracted from PubMed records using a text-mining technique and second, determining whether there is improvement in performance by limiting response processes by drugs sharing the same side effect to frequent ones alone.ResultsThe multi-level network (the process-drug-side effect network) was built by merging the drug-biological process network and the drug-side effect network. We generated a network of 74 drugs-168 side effects-2209 biological process relation resources. The preliminary results showed that the process-drug-side effect network was able to find meaningful relationships between biological processes and side effects in an efficient manner.ConclusionsWe propose a novel process-drug-side effect network for discovering the relationship between biological processes and side effects. By exploring the relationship between drugs and phenotypes through a multi-level network, the mechanisms underlying the effect of specific drugs on the human body may be understood.
Direct quantitative mapping of the density‐of‐states, named the photo‐excited charge‐collection technique, for the interface traps at the n‐ZnO and/or p‐pentacene thin‐film transistor channel is implemented by using monochromatic photons which are carried by optical fibers and are probed onto thin‐film transistors.
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