Low-power display system enabled by combining oxide semiconductor and neural network technologies

An oxide semiconductor (OS)-based field effect transistor (OSFET) exhibits the advantage of having an extremely low off-state current; moreover, the OSFET displays an off-state current that is ten orders of magnitude lower than that of a CMOS-FET [1]. Recently, numerous applications that harness this feature have been reported [2]. For instance, charge leakage from a data retention node of a pixel significantly decreases when the display incorporates OSFETs in its pixel circuit (OS display) [3, 4]. This minimizes degradation in the image quality when the displayed image is static despite using lower refresh rates. Consequently, the consumed power of the display driver circuit can be reduced by a large margin. This driving method is termed idling stop (IDS) driving. The OSFET’s low-leakage can also effectively enable a type of ULSICs that we term OS-large-scale integrated circuits (OSLSI) [5, 6]. Please click Additional Files below to see the full abstract

Editorial: Conflicts

The Editorial Board reflects on the theme of 'conflict', as observed in the work published in this issue, and in the wider world

Role of PSCs in Regeneration of Remnant Pancreas after PX

Background and objectives Mechanism of regeneration of remnant pancreas after partial pancreatectomy (PX) is still unknown. In this study, effect of siRNA against the collagen specific chaperone, HSP47, which inhibits collagen secretion from activated pancreas stellate cells (aPSCs), and induces their apoptosis, on regeneration of remnant pancreas was determined. Methods Pancreatectomy was performed according to established methods. Proliferation of cells was assessed by BrdU incorporation. Immunostaining of HSP47 was employed to identify PSCs. Progenitor cells were identified by SOX9 staining. Acinar cells were immunostained for amylase. Co-culture of acinar cells with aPSCs were carried out in a double chamber with a cell culture insert. siRNA HSP47 encapsulated in vitamin A-coupled liposome (VA-lip siRNA HSP47) was delivered to aPSCs by iv injection. Results In remnant pancreas of 90% PX rat, new areas of foci were located separately from duodenal areas with normal pancreatic features. After PX, BrdU uptake of acinar cells and islet cells significantly increased, but was suppressed by treatment with VA-lip siRNA HSP47. BrdU uptake by acinar cells was augmented by co-culturing with aPSCs and the augmentation was nullified by siRNA HSP47. BrdU uptake by progenitor cells in foci area was slightly enhanced by the same treatment. New area which exhibited intermediate features between those of duodenal and area of foci, emerged after the treatment. Conclusion aPSCs play a crucial role in regeneration of remnant pancreas, proliferation of acinar and islet cells after PX through the activity of secreted collagen. Characterization of new area emerged by siRNA HSP47 treatment as to its origin is a future task

Investigating nuclear shell structure in the vicinity of 78Ni: Low-lying excited states in the neutron-rich isotopes 80,82Zn

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The Constrained Maximal Expression Level Owing to Haploidy Shapes Gene Content on the Mammalian X Chromosome.

X chromosomes are unusual in many regards, not least of which is their nonrandom gene content. The causes of this bias are commonly discussed in the context of sexual antagonism and the avoidance of activity in the male germline. Here, we examine the notion that, at least in some taxa, functionally biased gene content may more profoundly be shaped by limits imposed on gene expression owing to haploid expression of the X chromosome. Notably, if the X, as in primates, is transcribed at rates comparable to the ancestral rate (per promoter) prior to the X chromosome formation, then the X is not a tolerable environment for genes with very high maximal net levels of expression, owing to transcriptional traffic jams. We test this hypothesis using The Encyclopedia of DNA Elements (ENCODE) and data from the Functional Annotation of the Mammalian Genome (FANTOM5) project. As predicted, the maximal expression of human X-linked genes is much lower than that of genes on autosomes: on average, maximal expression is three times lower on the X chromosome than on autosomes. Similarly, autosome-to-X retroposition events are associated with lower maximal expression of retrogenes on the X than seen for X-to-autosome retrogenes on autosomes. Also as expected, X-linked genes have a lesser degree of increase in gene expression than autosomal ones (compared to the human/Chimpanzee common ancestor) if highly expressed, but not if lowly expressed. The traffic jam model also explains the known lower breadth of expression for genes on the X (and the Z of birds), as genes with broad expression are, on average, those with high maximal expression. As then further predicted, highly expressed tissue-specific genes are also rare on the X and broadly expressed genes on the X tend to be lowly expressed, both indicating that the trend is shaped by the maximal expression level not the breadth of expression per se. Importantly, a limit to the maximal expression level explains biased tissue of expression profiles of X-linked genes. Tissues whose tissue-specific genes are very highly expressed (e.g., secretory tissues, tissues abundant in structural proteins) are also tissues in which gene expression is relatively rare on the X chromosome. These trends cannot be fully accounted for in terms of alternative models of biased expression. In conclusion, the notion that it is hard for genes on the Therian X to be highly expressed, owing to transcriptional traffic jams, provides a simple yet robustly supported rationale of many peculiar features of X's gene content, gene expression, and evolution

Weak Electric Current Treatment to Artificially Enhance Vascular Permeability in Embryonated Chicken Eggs

Technologies that overcome the barrier presented by vascular endothelial cells are needed to facilitate targeted delivery of drugs into tissue parenchyma by intravenous administration. We previously reported that weak electric current treatment (ET: 0.3–0.5 mA/cm2) applied onto skin tissue in a transdermal drug delivery technique termed iontophoresis induces cleavage of intercellular junctions that results in permeation of macromolecules such as small interfering RNA and cytosine-phosphate-guanine (CpG) oligonucleotide through the intercellular space. Based on these findings, we hypothesized that application of ET to blood vessels could promote cleavage of intercellular junctions that artificially induces increase in vascular permeability to enhance extravasation of drugs from the vessels into target tissue parenchyma. Here we investigated the effect of ET (0.34 mA/cm2) on vascular permeability using embryonated chicken eggs, which have blood vessels in the chorioallantoic membrane (CAM), as an animal model. ET onto the CAM of the eggs significantly increased extravasation of intravenously injected calcein (M.W. 622.6), a low molecular weight compound model, and the macromolecule fluorescein isothiocyanate (FITC)-dextran (M.W. 10000). ET-mediated promotion of penetration of FITC-dextran through vascular endothelial cells was also observed in transwell permeability assay using monolayer of human umbilical vein endothelial cells without induction of obvious cellular damage. Confocal microscopy detected remarkable fluorescence derived from injected FITC-dextran in blood vessel walls. These results in embryonated chicken eggs suggest that ET onto blood vessels could artificially enhance vascular permeability to facilitate extravasation of macromolecules from blood vessels

Effective Anticancer Therapy by Combination of Nanoparticles Encapsulating Chemotherapeutic Agents and Weak Electric Current

Delivery of medicines using nanoparticles via the enhanced permeability and retention (EPR) effect is a common strategy for anticancer chemotherapy. However, the extensive heterogeneity of tumors affects the applicability of the EPR effect, which needs to overcome for effective anticancer therapy. Previously, we succeeded in the noninvasive transdermal delivery of nanoparticles by weak electric current (WEC) and confirmed that WEC regulates the intercellular junctions in the skin by activating cell signaling pathways (J. Biol. Chem., 289, 2014, Hama et al.). In this study, we applied WEC to tumors and investigated the EPR effect with polyethylene glycol (PEG)-modified doxorubicin (DOX) encapsulated nanoparticles (DOX-NP) administered via intravenous injection into melanoma-bearing mice. The application of WEC resulted in a 2.3-fold higher intratumor accumulation of nanoparticles. WEC decreased the amount of connexin 43 in tumors while increasing its phosphorylation; therefore, the enhancing of intratumor delivery of DOX-NP is likely due to the opening of gap junctions. Furthermore, WEC combined with DOX-NP induced a significant suppression of tumor growth, which was stronger than with DOX-NP alone. In addition, WEC alone showed tumor growth inhibition, although it was not significant compared with non-treated group. These results are the first to demonstrate that effective anticancer therapy by combination of nanoparticles encapsulating chemotherapeutic agents and WEC

Enhancement of cerebroprotective effects of lipid nanoparticles encapsulating FK506 on cerebral ischemia/reperfusion injury by particle size regulation

Delivery of cerebroprotective agents using liposomes has been demonstrated to be useful for treating cerebral ischemia/reperfusion (I/R) injury. We previously reported that intravenous administration of liposomes with diameters of 100 nm showed higher accumulation in the I/R region compared with larger liposomes (>200 nm) by passage through the disintegrated blood-brain barrier, suggesting a size-dependence for liposome-mediated drug delivery. Based on these findings, we hypothesized that regulation of liposomal particle size (100 nm in cerebral I/R model rats. Intravenously administered smaller LNP (ca. 60 nm) exhibited wider accumulation and diffusivity in the brain parenchyma of the I/R region compared with larger LNP (>100 nm). Importantly, treatment with LNP encapsulating the cerebroprotective agent FK506 (FK-LNP) with particle sizes 100 nm, and also significantly ameliorated brain injury. These results suggest that particle size regulation of LNP to sizes <100 nm can enhance the therapeutic effect of encapsulated drugs for treatment of cerebral I/R injury, and that FK-LNP could be a promising cerebroprotective agent

A simple, fast, and orientation-controllable technology for preparing antibody-modified liposomes

Modification with antibodies is a useful strategy for the delivery of nanoparticles to target cells. However, the complexity of the required chemical modifications makes them time-consuming and low efficiency, and the orientation of the antibody is challenging to control. To develop a simple, fast, effective, and orientation-controllable technology, we employed staphylococcal protein A, which can bind to the Fc region of antibodies, as a tool for conjugating antibodies to nanoparticles. Specifically, we modified the C-domain dimer of protein A to contain a lysine cluster to create a molecule, DPACK, that would electrostatically bind to anionic liposomes. Using this protein, antibody-modified liposomes can be prepared in 35 minutes with two steps: (1) interaction of DPACK with liposomes and (2) interaction of an antibody with DPACK-modified liposomes. Binding efficiencies of DPACK with liposomes and IgG with DPACK-modified liposomes were 75% and 72-84%, respectively. Uptake of liposomes modified with anti-epidermal growth factor receptor (EGFR) antibodies via DPACK by EGFR-expressing cancer cells was significantly higher than that of unmodified liposomes, and the liposomes accumulated in tumors and colocalized with EGFR. This simple, fast, effective and orientation-controllable technology for preparing antibody-modified liposomes will be useful for active targeting drug delivery