Since the report by Nomura et al. [1] thin film transistors (TFTs) based on amorphous oxide semiconductors (AOSs) have emerged as a promising technology, particularly for active-matrix TFT-based backplanes, due to their superior electrical performance when compared with conventional amorphous silicon and polycrystalline silicon TFTs. Among the various AOSs, amorphous indiumgallium-zinc-oxide (a-IGZO) TFTs have high field-effect mobilities exceeding that of a-Si by a factor of 10 2 , a small subthreshold swing, good uniformity attributed to the amorphous structure, a low off current, good stability under electrical stress, and can be processed at low temperatures. Several research groups have already presented a-IGZO based working devices with remarkable electrical and optical properties. We have recently demonstrated high performance a-IGZO TFTs which exhibited a field effect mobility µ FE of 19.4 cm 2 /Vs, a subthreshold swing S of 0.5 V/decade, and a ratio of on and off current I ON /I OFF of 10 8 , respectively [2].Despite recent successes, some outstanding issues related to the a-IGZO TFT electrical performance still remain to be resolved, such as obtaining good electrical contact between source/drain (S/D) electrodes. A previous report [3] on contact resistance of candidate metal electrodes and a-IGZO showed the trend that the contact resistance decreases with the work function of the metallic electrode. High work function electrodes showed Schottky contacts, while reactive electrodes did ohmic contact. However, using reactive metals for an electrical contact require a high reproducibility of the process.We focus here on an investigation of Cu electrodes to obtain good ohmic characteristics in a-IGZO based TFTs. Specifically, we discuss the S/D series resistances and their effects on the TFT performance. The TFT S/D series resistance, the intrinsic field effect mobility µ FE-i , transfer length L T , and effective contact resistance R C-eff were extracted by the well-known transmission line method (TLM) using a series of TFTs with different channel lengths.The bottom gate type a-IGZO TFTs with staggered structure were prepared on heavily doped n-type silicon substrates having a LPCVD SiN x layer of 100 nm. Thin films of a-IGZO (80 nm thick) were deposited using DC magnetron sputtering with sintered InGaZnO 4 (99.999% purity) as the target material. Sputtering was performed at room temperature in an argon atmosphere with an oxygen partial pressure of 4%. A 4 inch diameter ceramic target, This paper focuses on the viability of low-resistivity electrode material (Cu) for source/drain electrodes in thin film transistors (TFTs). The effective resistances between Cu source/drain electrodes and amorphous indium gallium zinc oxide (a-IGZO) thin-film transistors were examined. Intrinsic TFT parameters were extracted by the transmission line method (TLM) using a series of TFTs with different channel lengths measured at a low source/drain voltage. The TFTs fabricated with Cu source/drain electrodes showed good transfe...

Background Alzheimer’s disease (AD) pathology is associated with complex interactions among multiple factors, involving an intertwined network of various signaling pathways. The polypharmacological approach is an emerging therapeutic strategy that has been proposed to overcome the multifactorial nature of AD by targeting multiple pathophysiological factors including amyloid-β (Aβ) and phosphorylated tau. We evaluated a blood-brain barrier penetrating phosphodiesterase 5 (PDE5) inhibitor, mirodenafil (5-ethyl-2-7-n-propyl-3,5-dihydrro-4H-pyrrolo[3,2-d]pyrimidin-4-one), for its therapeutic effects on AD with polypharmacological properties. Methods To evaluate the potential of mirodenafil as a disease-modifying AD agent, mirodenafil was administered to test its effects on the cognitive behaviors of the APP-C105 AD mouse model using the Morris water maze and passive avoidance tests. To investigate the mechanisms of action that underlie the beneficial disease-modifying effects of mirodenafil, human neuroblastoma SH-SY5Y cells and mouse hippocampal HT-22 cells were used to show mirodenafil-induced alterations associated with the cyclic guanosine monophosphate (cGMP)/cGMP-dependent protein kinase (PKG)/cAMP-responsive element-binding protein (CREB) pathway, apoptotic cell death, tau phosphorylation, amyloidogenesis, the autophagy-lysosome pathway, glucocorticoid receptor (GR) transcriptional activity, and the Wnt/β-catenin signaling. Results Here, mirodenafil is demonstrated to improve cognitive behavior in the APP-C105 mouse model. Mirodenafil not only reduced the Aβ and phosphorylated tau burdens in vivo, but also ameliorated AD pathology induced by Aβ through the modulation of the cGMP/PKG/CREB signaling pathway, glycogen synthase kinase 3β (GSK-3β) activity, GR transcriptional activity, and the Wnt/β-catenin signaling in neuronal cells. Interestingly, homodimerization and nuclear localization of GR were inhibited by mirodenafil, but not by other PDE5 inhibitors. In addition, only mirodenafil reduced the expression levels of the Wnt antagonist Dickkopf-1 (Dkk-1), thus activating the Wnt/β-catenin signaling. Conclusions These findings strongly suggest that the PDE5 inhibitor mirodenafil shows promise as a potential polypharmacological drug candidate for AD treatment, acting on multiple key signaling pathways involved in amyloid deposition, phosphorylated tau burden, the cGMP/PKG/CREB pathway, GSK-3β kinase activity, GR signaling, and the Wnt/β-catenin signaling. Mirodenafil administration to the APP-C105 AD mouse model also improved cognitive behavior, demonstrating the potential of mirodenafil as a polypharmacological AD therapeutic agent.

As the NAND flash market demand for larger capacity with low cost increases, the feature-size scaling and multi-level per bit have been developed. In this paper, we present the newly adopted operation algorithms and their results such as intelligent ISPE(Incremental Step Pulse Erase), various biasing in grouped W/Ls and VNR(Virtual Negative Read) in TLC(Triple Level Cell) NAND flash.

Background The accumulation of amyloid‐b (Ab) in the brain is the primary pathological hallmark of Alzheimer’s disease (AD). Aggregated Ab is associated with cytotoxicity by a variety of mechanisms leading to neuronal apoptosis and synaptic impairments. Here, we present experimental evidence showing that AR1001, a highly selective and potent phosphodiesterase 5 (PDE5) inhibitor, acts as a polypharmacological agent for the treatment of AD by promoting neuronal cell survival and inhibiting Ab accumulation. Method The in vitro toxic effects of Ab were examined using the human neuroblastoma derived SH‐SY5Y cell line and mouse hippocampal neuronal HT‐22 cell line. Cell‐free Thioflavin T (ThT) fluorescence assay and SDS‐PAGE with PICUP (Photo‐Induced Cross‐Linking of Unmodified Proteins) of Ab plaques were employed to test inhibition of Ab aggregate formation and reduction of preformed oligomers and fibrils. To identify transcription factors responsible for inhibitory effects of AR1001 on Amyloid Precursor Protein (APP) / b‐site APP cleaving enzyme 1 (BACE1) expression, the Transcription Factor Profiling Plate Array was used to monitor the activation/inhibition of various transcription factors. 5XFAD transgenic mice were used to evaluate Ab42 induced neurodegeneration and amyloid plaque formation. NSE/APP‐C105 transgenic mice were used to test spatial and learning memory in the Morris water maze test and the passive avoidance test. Result AR1001 markedly increased cGMP levels and activated cGMP/cGMP‐dependent protein kinase/cAMP responsive element‐binding protein (CREB) cascade in Ab‐treated SH‐SY5Y cells, promoting neuronal cell survival. In Ab‐treated HT‐22 cells, downregulation of Glucocorticoid Receptor (GR) transcriptional activity by AR1001 was responsible for reduced expression of APP, BACE1 and Dickkopf‐1 (Dkk1). In addition, AR1001 disrupted pre‐formed Ab42 fibrils in vitro. Interestingly, AR1001 reduced deposition of Aβ plaques in 5XFAD transgenic mouse brain by activating the autophagic process. Finally, AR1001 significantly improved memory functions in NSE/APP‐C105 mice. Conclusion Our findings strongly support that AR1001 has benefits against the accumulation of Ab and cognitive deficits in AD mouse models. We have demonstrated that AR1001 serves as a polypharmacological agent to inhibit PDE5 activity, promoting cell survival, and downregulate GR activity, reducing APP/BACE1 expression.

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